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Metastatic Tumors (metastatic + tumor)
Selected AbstractsDetection of Micrometastasis in the Sentinel Lymph Node via Lymphoscintigraphy for a Patient With In-Transit Metastatic MelanomaDERMATOLOGIC SURGERY, Issue 9 2003Chih-Hsun Yang MD Background. Lymphoscintigraphy and sentinel lymph node (SLN) biopsy are highly accurate methods of detecting regional lymph node status for melanoma. Previously, these procedures were mainly performed in patients with primary melanoma before wide local excision. Objective. To present a case with in-transit recurrence melanoma using lymphoscintigraphy and SLN biopsy for detection of nodal basin status. Methods. The patient discussed here had a subungual melanoma that developed as an in-transit metastatic melanoma on the pretibia area 2 years after right big toe amputation. By using lymphoscintigraphy and SLN biopsy technique with injection of technetium-99m colloid around the in-transit metastatic site, the first node (SLN) draining the in-transit metastatic tumor was identified and harvested on the right inguinal area. Immediate right inguinal node dissection was subsequently performed. Results. Under thorough histologic examination, the first node (SLN) draining the in-transit metastatic tumor was the only node that contained micrometastatic tumor cells in the surgical specimens. Conclusion. Lymphoscintigraphy and SLN biopsy techniques are sensitive procedures for detecting the regional nodal basin micrometastasis in in-transit recurrence melanoma patients. [source] Nodal sampling in pancreaticoduodenectomy: does it change our management?HPB, Issue 6 2007ROOZBEH RASSADI Abstract Background. Lymph node involvement in periampullary malignancy is the single most important factor in predicting survival in pancreaticoduodenectomy (PD). The role of nodal sampling in PD has not been well evaluated. This study evaluates the utility of nodal sampling of nodal stations 8 and 12, which are easily dissected early in PD, in overall final nodal status. Patients and methods. Fifty patients underwent PD at a single institution by a one surgeon over a 15 month period. Nodal stations 8 and 12 were sent separately for pathologic evaluation. Twenty-eight patients had a final diagnosis of periampullary malignancy. Demographic and pathologic data were collected retrospectively from patient charts. Positive and negative predictive values of nodes 8 and 12 were evaluated. Results. Eighteen of 28 patients with a diagnosis of periampullary malignancy had pathologically negative nodes 8 and 12, and a final nodal status (all peripancreatic lymph nodes) negative for nodal involvement. Nine of 28 patients had a negative nodal sampling result, but a positive final nodal status for metastatic tumor. The remaining four patients had both positive nodal sampling and final nodal status for metastatic tumor. The negative predictive value of negative nodes 8 and 12 was 0.625. Conclusion. The negative predictive of a negative node 8 and 12 of 0.625 suggests that the decision to proceed with or abort PD should not be based on intraoperative evaluation of these nodes. Performance of PD should be undertaken if technically feasible, and not based on intraoperative nodal assessment. [source] Hepatic arterial cannulation using the side holed catheterJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Masashi Watanabe MD Abstract Background Hepatic arterial infusion chemotherapy (HAIC) has been recognized as one of the effective treatments for patients with hepatic metastatic tumor. However it is difficult to perform HAIC in the long term without complications. This report describes the laparotomic approach using the side holed catheter, which is a novel method of implanting a catheter-port system. Methods and Results We designed a new anti-thrombotic catheter for HAIC. This catheter is tapered from 5F (diameter of shaft) to 3.3F (diameter at tip), and a side hole is opened 7 cm from the tip of catheter. This catheter is inserted from the gastroduodenal artery to the common hepatic artery (CHA), and the tip is put in the aorta or in the splenic artery. The side hole is adjusted distal to the CHA. In our surgical department, our new catheter was inserted in four patients at the time of their abdominal surgery. The cannulation was performed successfully in all patients. In two of them, HAIC was finished without problems at 6 months after starting, and two were still treated by HAIC at 9 and 8 months after starting. Conclusions Initial results from a study of a new method of implanting a catheter-port system in the hepatic artery using the new tapering side hole catheter suggest that this method may enable operators to avoid complicated selective coiling and may lower the incidence of hepatic artery occlusion in patients receiving long-term HAIC. J. Surg. Oncol. 2005;91:145,149. © 2005 Wiley-Liss, Inc. [source] Aggressive invasive micropapillary salivary duct carcinoma of the parotid glandPATHOLOGY INTERNATIONAL, Issue 5 2008Hidetaka Yamamoto The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor. [source] Pulmonary capillary hemangiomatosis incidentally detected in a lobectomy specimen for a metastatic colon cancerPATHOLOGY INTERNATIONAL, Issue 6 2006Suzuko Moritani Pulmonary capillary hemangiomatosis is a rare vascular proliferative disease of unknown etiology. The common clinical features are slowly progressive and finally fatal pulmonary hypertension. The clinical diagnosis is usually difficult. Because most reported cases are of autopsy, little is known about its incipient lesion and natural history. Presented herein is a case of pulmonary capillary hemangiomatosis incidentally detected in a surgically resected lung for a metastatic colon cancer. The patient was a 60-year-old Japanese woman with a history of sigmoid colon cancer 3 years previously. The patient had undergone a right lower lobectomy for a metastatic tumor in the hilar region and a thoracoscopic tumorectomy of the peripheral area of the left upper lobe. Except for an episode of hemoptysis 2 weeks prior to the lung surgery, there were no other clinical symptoms characteristic of pulmonary capillary hemangiomatosis. The non-tumor area of right lower lobe showed multiple foci of capillary proliferation affecting alveolar walls, interlobular septa and pleura associated with patchy hemorrhage. There was a minor degree of vascular and bronchial involvement by capillary proliferation. It is suggested this particular case is an incidentally detected clinically incipient stage of pulmonary capillary hemangiomatosis. Passive congestion secondary to metastatic colon cancer in the hilar region may have contributed to the pathogenesis of this lesion. [source] Histopathological characterization of aortic intimal sarcoma with multiple tumor emboliPATHOLOGY INTERNATIONAL, Issue 11 2000Naoki Nishida A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor. [source] The number of lymph nodes with metastasis predicts survival in patients with esophageal or esophagogastric junction adenocarcinoma who receive preoperative chemoradiationCANCER, Issue 5 2006Yan Gu M.D. Abstract BACKGROUND The survival of patients with locoregional adenocarcinoma of the esophagus or the esophagogastric junction (EGJ) who receive preoperative chemoradiation is reported to be better among patients who achieve a pathologic complete response than among patients who have residual tumor, including lymph node (LN) metastasis. However, the prognostic significance of the number of LNs with residual metastasis remains unclear. METHODS The authors studied 187 consecutive patients who received chemoradiation followed by an esophagectomy. The number of positive LNs and the size of metastatic tumor in each positive LN were examined with regard to overall survival (OS) and recurrence-free survival (RFS). RESULTS A pathologic complete response was achieved by 29% of patients. No LN metastasis (posttherapy pathologic negative LN status [ypN0]) was present in 49% of patients who had residual carcinoma, and LN metastasis (ypN1) was present in 51% of patients. The 5-year OS and 2-year RFS rates achieved by patients who had 1 positive LN (34% and 45%, respectively) were similar to the rates achieved by patients in the ypN0 group (38% [P = 0.84] and 50% [P = 0.77], respectively) but were significantly better than the rates achieved by patients who had , 2 positive LNs (6% [P = 0.02] and 18% [P = 0.01], respectively). The size of metastatic tumor in LNs among patients who had 1 positive LN was a prognostic factor (, 4 mm vs. < 4 mm; P = 0.04). In multivariate analysis, OS was better in patients who had 1 LN metastasis among patients in the ypN1 group (P = 0.02) independent of their posttherapy pathologic tumor status. CONCLUSIONS The current results suggested that the number of LNs with metastasis is an independent prognostic factor in patients with residual adenocarcinoma of the esophagus or the EGJ after preoperative chemoradiation. The authors suggest modification of the tumor-lymph node-metastasis (TNM) staging classification (ypTNM) to include the number of positive LNs in the ypN1 category. Cancer 2006. © 2006 American Cancer Society. [source] Open-sky biopsy of ciliary body or choroidal tumors of undetermined origin: utility and safetyACTA OPHTHALMOLOGICA, Issue 2009A SCHALENBOURG Purpose In the presence of a ciliary body or choroidal tumor of undetermined origin, an open-sky biopsy is performed in selected cases to establish a diagnosis and specify the therapeutic approach. We explored the frequency and reliability of this diagnostic procedure. Methods Retrospective, consecutive, histopathologic case series of 30 biopsies since 1989 of ciliary body or choroidal tumors of undetermined origin. Results Eighteen tumors originated from the ciliary body, 12 from the choroid. Diagnosis was respectively adenoma/adenocarcinoma (4;0), mesectodermal leiomyoma (4;1), metastatic tumor (2;0), melanocytic tumor (4;5), lymphoma (1;3); hemangioma (1;0) or posterior nodular scleritis (0;3). In 2 cases, there was insufficient material to make a diagnosis. There were no cases where the biopsy complicated local or systemic tumor control. Conclusion Open-sky biopsy is only performed in cases whose clinical appearance doesn't permit to confidently establish a diagnosis; its goal is to guide the therapeutic approach. [source] The art and science of oral examinationDERMATOLOGIC THERAPY, Issue 3 2010Rania Agha ABSTRACT Performing an accurate oral examination is an integral part of a complete dermatological evaluation. As dermatologists, we are frequently asked to assess and treat numerous oral pathologies, which include, but are not limited to, normal variants, infections, ulcers, granulomas, lymphomas, as well as primary and metastatic tumors of the mouth and lips. The oral mucosa can be the window through which one can see and make numerous systemic diagnoses. Some clinicians are apprehensive about performing this evaluation, or feel that this examination is outside of their realm of expertise. These concerns may reflect limited exposure and education during training. Therefore, this article aimed to educate the readers on how to complete an oral examination, demonstrate normal variants, and highlight potential pitfalls and limitations of performing oral biopsies. [source] Diagnostic value of needle aspiration cytology (NAC) in the assessment of palpable inguinal lymph nodes: A study of 210 casesDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2003F.I.A.C., Raj K. Gupta M.D. Abstract The aim of this study was to evaluate the diagnostic value of needle aspiration cytology (NAC) in the assessment of palpable inguinal lymph nodes, which were analyzed in 210 cases. NAC in all the cases were performed by the conventional aspiration method and cytologic examination was done on site after staining smears with the Papanicolaou method. In addition, Diff-Quik-stained air-dried smears, Papanicolaou-stained fixed smears, and filter preparations from needle washings and hematoxylin-eosin-stained sections of cell blocks were studied. The NAC diagnosis was supported by examining cell blocks in 92/210 cases which showed a reliable histologic architecture; further support was also obtained with a tissue biopsy in 9/12 cases of inflammatory lesions, 7/7 cases with a suspicious diagnosis, 20/26 cases of melanomas, 15/15 cases of lymphomas, and/or a comparison with the primary tumor in other cases of metastatic tumors. Additionally, immunoperoxidase and/or histochemical stains were done. Twelve cases were diagnosed as inflammatory lesions and 88 cases were regarded as negative (normal cellular elements n = 40; reactive elements n = 48). In 58 cases a variety of metastatic tumors were diagnosed (melanoma n = 26; others n = 32) and in 15 cases a diagnosis of lymphoma was made. Seven cases were diagnosed as suspicious of malignancy and 30 cases were unsatisfactory due to scanty/acellular samples (despite 2,3 repeat samplings). However, in five of these malignant tumors were later found on a biopsy which was done due to a persistent and continued enlargement of lymph node(s). The sensitivity was 91.7%, specificity 98.2%, positive predictive value (PPV) 97.7.%, and negative predictive value (NPV) was 95.45%. Based on our study we feel that NAC as a first line of investigation is not only useful in the diagnosis of lesions in inguinal lymph nodes, but can also help in deciding on an appropriate management. Also, histologic architecture from cell blocks can be correlated with cytology and such material can be used for histochemical and immunomarker studies. Diagn. Cytopathol. 2003;28:175,180. © 2003 Wiley-Liss, Inc. [source] Breast masses in males: Multi-institutional experience on fine-needle aspirationDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2002Momin T. Siddiqui M.D. Abstract Male breast masses are uncommon pathologic findings. They are rarely aspirated, resulting in limited cytopathologic experience. The following study describes the cytopathology of male breast lesions from data collected for a period of 10 yr from three large institutions. A total of 14,026 breast aspirations were performed of which 614 were from male patients. All cases were reviewed and correlated with the appropriate clinicopathologic follow-up. The FNA diagnoses were as follows: benign, 427 cases (gynecomastia 353, fat necrosis 21, miscellaneous 53); malignant, 32 cases (ductal carcinoma nos 15, metastatic tumors 17); and atypical/suspicious, 61 cases. Ninety-four cases were nondiagnostic due to scant cellularity. Male breast aspirates accounted for 4.3% of the total breast FNAs performed. The clinicopathologic follow-up in both the benign and malignant categories showed 100% correlation. The overall sensitivity was 95.3%, specificity was 100%, and diagnostic accuracy was 98%. A relatively high specimen unsatisfactory rate was seen (>15%). The commonest cytopathologic diagnosis was gynecomastia, followed by ductal carcinoma. Florid duct atypia in gynecomastia may mimic adenocarcinoma, necessitating a higher threshold for cytopathologic interpretation for malignancy in males. Diagn. Cytopathol. 2002;26:87,91; DOI 10.1002/dc.10066 © 2002 Wiley-Liss, Inc. [source] Clonal expansions of 6-thioguanine resistant T lymphocytes in the blood and tumor of melanoma patients,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2008Mark R. Albertini Abstract The identification of specific lymphocyte populations that mediate tumor immune responses is required for elucidating the mechanisms underlying these responses and facilitating therapeutic interventions in humans with cancer. To this end, mutant hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficient (HPRT -) T-cells were used as probes to detect T-cell clonal amplifications and trafficking in vivo in patients with advanced melanoma. Mutant T-cells from peripheral blood were obtained as clonal isolates or in mass cultures in the presence of 6-thioguanine (TG) selection and from tumor-bearing lymph nodes (LNs) or metastatic melanoma tissues by TG-selected mass cultures. Nonmutant (wild-type) cells were obtained from all sites by analogous means, but without TG selection. cDNA sequences of the T-cell receptor (TCR) beta chains (TCR-,), determined directly (clonal isolates) or following insertion into plasmids (mass cultures), were used as unambiguous biomarkers of in vivo clonality of mature T-cell clones. Clonal amplifications, identified as repetitive TCR-, V-region, complementarity determining region 3 (CDR3), and J-region gene sequences, were demonstrated at all sites studied, that is, peripheral blood, LNs, and metastatic tumors. Amplifications were significantly enriched among the mutant compared with the wild-type T-cell fractions. Importantly, T-cell trafficking was manifested by identical TCR-, cDNA sequences, including the hypervariable CDR3 motifs, being found in both blood and tissues in individual patients. The findings described herein indicate that the mutant T-cell fractions from melanoma patients are enriched for proliferating T-cells that infiltrate the tumor, making them candidates for investigations of potentially protective immunological responses. Environ. Mol. Mutagen., 2008. Published 2008 Wiley-Liss, Inc. [source] Treatment response to transcatheter arterial embolization and chemoembolization in primary and metastatic tumors of the liverHPB, Issue 6 2008Avo Artinyan Abstract Introduction. Transcatheter arterial embolization (TAE) and chemoembolization (TACE) are increasingly used to treat unresectable primary and metastatic liver tumors. The purpose of this study was to determine the objective response to TAE and TACE in unresectable hepatic malignancies and to identify clinicopathologic predictors of response. Materials and methods. Seventy-nine consecutive patients who underwent 119 TAE/TACE procedures between 1998 and 2006 were reviewed. The change in maximal diameter of 121 evaluable lesions in 56 patients was calculated from pre and post-procedure imaging. Response rates were determined using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The Kaplan-Meier method was used to compare survival in responders vs. non-responders and in primary vs. metastatic histologies. Results. TAE and TACE resulted in a mean decrease in lesion size of 10.3%±1.9% (p<0.001). TACE (vs. TAE) and carcinoid tumors were associated with a greater response (p<0.05). Lesion response was not predicted by pre-treatment size, vascularity, or histology. The RECIST partial response (PR) rate was 12.3% and all partial responders were in the TACE group. Neuroendocrine tumors, and specifically carcinoid lesions, had a significantly greater PR rate (p<0.05). Overall survival, however, was not associated with histology or radiologic response. Discussion. TAE and TACE produce a significant objective treatment response by RECIST criteria. Response is greatest in neuroendocrine tumors and is independent of vascularity and lesion size. TACE appears to be superior to TAE. Although an association of response with improved survival was not demonstrated, large cohort studies are necessary to further define this relationship. [source] Mesenchymal stem cells enhance growth and metastasis of colon cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2010Kei Shinagawa Abstract Recently, mesenchymal stem cells (MSCs) were reported to migrate to tumor stroma as well as injured tissue. We examined the role of human MSCs in tumor stroma using an orthotopic nude mice model of KM12SM colon cancer. In in vivo experiments, systemically injected MSCs migrated to the stroma of orthotopic colon tumors and metastatic liver tumors. Orthotopic transplantation of KM12SM cells mixed with MSCs resulted in greater tumor weight than did transplantation of KM12SM cells alone. The survival rate was significantly lower in the mixed-cell group, and liver metastasis was seen only in this group. Moreover, tumors resulting from transplantation of mixed cells had a significantly higher proliferating cell nuclear antigen labeling index, significantly greater microvessel area and significantly lower apoptotic index. Splenic injection of KM12SM cells mixed with MSCs, in comparison to splenic injection of KM12SM cells alone, resulted in a significantly greater number of liver metastases. MSCs incorporated into the stroma of primary and metastatic tumors expressed ,-smooth muscle actin and platelet-derived growth factor receptor-, as carcinoma-associated fibroblast (CAF) markers. In in vitro experiments, KM12SM cells recruited MSCs, and MSCs stimulated migration and invasion of tumor cells through the release of soluble factors. Collectively, MSCs migrate and differentiate into CAFs in tumor stroma, and they promote growth and metastasis of colon cancer by enhancing angiogenesis, migration and invasion and by inhibiting apoptosis of tumor cells. [source] Nm23-H1 expression of metastatic tumors in the lymph nodes is a prognostic indicator of oral squamous cell carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Yi-Fen Wang Abstract We recently reported that low Nm23-H1 expression of primary oral squamous cell carcinoma (OSCC) was correlated with the occurrence of lymphatic metastasis. However, little is known about whether Nm23-H1 level of metastatic tumors in the cervical lymph nodes is reduced in comparison with primary oral cancers and its significance for patients' prognosis. By immunohistochemistry, we analyzed the Nm23-H1 expression in 52 pairs of OSCC specimens from primary oral cancers and their metastatic lymph nodes. Western blot analysis further confirmed the immunohistochemical interpretation. To verify the effects of Nm23-H1 on cell migration and invasion, we established several stable clones derived from a human OSCC cell line (SAS) by knockdown and overexpression. Wound-healing closure, transwell migration and invasion assays were performed to determine cell motility, migratory and invasive activities. Western blot analysis was carried out to evaluate cyclin A expression of OSCC cells with the altered Nm23-H1 levels following knockdown and overexpression. By immunohistochemistry, Nm23-H1 expression of metastatic lymph nodes was significantly lower than that of their primary oral cancers, supporting a role of Nm23-H1 in metastasis suppression. Negative Nm23-H1 interpretation of OSCC specimens, in either primary oral cancers or metastatic lymph nodes, indicated a poor survival outcome of patients. On the basis of in vitro studies of Nm23-H1 knockdown and overexpression, we demonstrated an inverse correlation between Nm23-H1 expression and the invasiveness of OSCC cells. Moreover, we observed the concomitant reduction in Nm23-H1 and cyclin A levels of metastatic tumors in both results of in vitro OSCC cells and ex vivo tumor specimens. © 2007 Wiley-Liss, Inc. [source] Melanoma patients respond to a new HLA-A*01-presented antigenic ligand derived from a multi-epitope region of melanoma antigen TRP-2INTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Annette Paschen Abstract Tyrosinase-related protein-2 (TRP-2) is a known target antigen of spontaneous cytotoxic T cell responses in melanoma patients. Its frequent expression in metastatic tumors suggests that it might be an ideal candidate antigen for T cell-based immunotherapy. To provide knowledge about TRP-2-derived T cell epitopes useful for immunotherapy we applied a "reverse immunology strategy" based on repeated in vitro peptide stimulation of peripheral blood lymphocytes (PBL) from normal donors with predicted HLA-A*01 ligands. This led to the identification of TRP-2181,190 as the first HLA-A*01-presented TRP-2-derived epitope. T-cell lines specific for peptide TRP-2181,190 could be established from PBL of 50% of the normal HLA-A*01+ donors tested. Such T cells responded specifically to autologous dendritic cells transduced virally with TRP-2, as well as to HLA-A*01+, TRP-2+ melanoma cells, although tumor cells had to be pretreated with IFN-, to become susceptible to T cell recognition. Interestingly, short-term in vitro peptide stimulation of PBL from HLA-A*01+ melanoma patients showed the presence of TRP-2181,190 -reactive CD8+ T cells in some donors, suggesting their in vivo sensitization. Because TRP-2181,190 overlaps with the known HLA-A*0201-presented epitope TRP-2180,188, an 11mer peptide encompassing both epitopes might be of specific value for vaccination of a broad population of melanoma patients. © 2005 Wiley-Liss, Inc. [source] Increased plasma MMP9 in integrin ,1-null mice enhances lung metastasis of colon carcinoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Xiwu Chen Abstract Inhibitors of matrix metalloproteinases (MMPs) were developed as anticancer agents based on the observation that MMPs facilitate local tumor spread and metastasis by promoting matrix degradation and cell migration. Unfortunately, these inhibitors were unsuccessful in the clinical treatment of several cancers, including lung cancer. A possible reason contributing to their failure is that MMP activity is critical for the generation of inhibitors of tumor angiogenesis, including angiostatin. Thus, MMPs might play opposing roles in tumor vascularization and invasion. To determine which effect of elevated MMP levels dominates in the progression of metastatic cancer, experimental lung metastasis assays were performed in integrin ,1-null mice, a genetic model for increased plasma levels of MMP9 and MMP9-generated angiostatin (Pozzi et al., Proc. Natl. Acad. Sci. USA 2000;97:2202,7). We show that while the number of lung colonies in integrin ,1-null mice was significantly increased compared to their wild-type counterparts, tumor volume was markedly reduced. In vivo treatment with the MMP inhibitor doxycycline resulted in a significant decrease in the number of lung colonies in both genotypes, but the tumors that formed were bigger and more vascularized. Increased tumor vascularization paralleled decreased plasma levels of MMP9 and consequent decreased angiostatin synthesis. These results demonstrate that while inhibition of MMPs prevents and/or reduces tumor invasion and lung metastasis, it has the paradoxical effect of increasing the size and vascularization of metastatic tumors due to decreased generation of inhibitors of endothelial cell proliferation. The continued growth of these large well-vascularized tumors may explain the poor efficacy of MMP inhibitors in lung cancer clinical trials. © 2005 Wiley-Liss, Inc. [source] Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004TETSUYA IMAO Abstract Background: Although a correlation between microvessel density (MVD) and tumor aggressiveness has been established for several malignancies, the data for renal cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD, we investigated the relationships between MVD and tumor stage, grade, size, occurrence of metastasis and patient survival. Methods: Tumor specimens from 70 patients with primary renal cell carcinoma were examined by immunohistochemical staining for CD34. Results: There was a tendency for MVD to decrease from G1 to G3 tumors or from stage T1 to T3 tumors, although this was not statistically significant. However, the MVD for 56 non-metastatic and 14 metastatic tumors were significantly different (P = 0.005) at 109 ± 67 and 58 ± 35 per ×400 field (mean ± SD), respectively. Microvessel density for 36 large and 34 small tumors was also significantly different (P < 0.0001) at 48 ± 22 and 142 ± 54 per ×400 field, respectively. The survival rate of patients with small, low grade and hypervascular tumors was significantly higher than that of patients with large (P = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional hazards regression analysis showed that tumor grade and size emerged as independent prognostic factors. Conclusion: High MVD in RCC was inversely associated with tumor aggressiveness, but MVD was not the independent prognostic factor. [source] Immunohistochemical localization of ornithine decarboxylase in skin tumorsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2000Masayori Kagoura Background: Ornithine decarboxylase (ODC) plays an important role in the biosynthesis of polyamines. Induction of ODC and polyamine synthesis has been demonstrated in neoplastic tumors and is thought to be related to the degree of malignancy. Methods: In this study, we investigated a series of basal cell epitheliomas (BCE), Bowen's disease, squamous cell carcinomas (SCC), and metastatic tumors of the skin using an antibody against ODC for immunohistochemistry. Results: Eight of 12 cases of BCE failed to show a positive reaction for ODC. In Bowen's disease, 5 of 13 cases diffusely showed positive reaction for ODC. Fourteen of 15 cases of SCC showed ODC expression, the intensity of which was decreased in the peripheral layer. At higher magnification, the distribution of ODC in the positive SCC cases showed granular and heterogenous patterns. Ten of 14 cases of metastatic skin tumors exhibited positive reactions, and well-differentiated adenocarcinomas tended to show more strongly positive than poorly-differentiated ones. Conclusions: These results support the conclusion that the intensity and the incidence of positive immunohistochemical staining for ODC correlate with the degree of cellular differentiation, and furthermore, that heterogenous distribution of ODC staining may be associated with heterogeneity of tumor cells. [source] Bone resorption activity of osteolytic metastatic lung and breast cancersJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2004Lih-Yuann Shih Abstract Production of bone resorption mediators and bone resorption activity were compared among osteolytic metastatic cancers, normal bone tissues, and soft tissue metastatic cancers to search for the possible factors leading to cancer-induced bone resorption. Twenty-five patients with untreated osteolytic metastatic breast or non-small cell lung cancers consisted of the study group. Normal bone tissues obtained from the same patient were used as internal controls; and tumor tissues from patients with soft tissue metastasis were used as external controls. Serum and urinary bone turnover markers were measured. Tissues harvested during surgery were subjected to tissue culture. The levels of prostaglandin E2 (PGE2), tumor necrosis factor-, (TNF-,), and interleukin-6 (IL-6) in the supernatant after 72 h of culture were measured. Bone resorption activity was measured by calcium release from cultured calvarias, and bone volume as well as osteoclast number in bone sections. Patients with osteolytic metastatic cancers showed significantly decreased serum osteocalcin, increased serum alkaline phosphatase, and urinary deoxypyridinoline levels. Osteolytic metastatic cancers produced significantly more PGE2 than both controls. Conditioned medium from osteolytic metastatic tumors showed significantly enhanced bone resorption activity, and indomethacin significantly reduced this activity. Levels of PGE2, and bone resorption activity increased in osteolytic tumor tissues than soft tissue metastatic tissues in the same patient indicated that the same tumor cells might respond differently to different microenvironments. Our observation showed that PGE2 was produced by osteolytic metastatic cancers and stimulated bone resorption in mice calvarias. PGE2 inhibitor may be applicable in reducing bone resorption by osteolytic metastatic cancers. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] The functional ,443T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factorMOLECULAR CARCINOGENESIS, Issue 1 2009Julia Schultz Abstract In the present report, the possible role of a recently described functional polymorphism of the osteopontin (OPN) promoter at position ,443 (,443T/C) for OPN expression in melanoma cells was addressed. As shown by real-time PCR analysis, melanoma metastases that were homozygous for the ,443C allele expressed significantly higher levels of OPN mRNA compared with those that were either heterozygous (,443T/C) or homozygous for the ,443T allele. In line with this, immunoblotting showed significantly enhanced baseline and bFGF-induced OPN protein expression in melanoma cell lines which were homozygous for the ,443C allele, compared with cell lines with other allelic variants. Similar results were obtained in in vitro luciferase assays. Chromatin immunoprecipitation (ChIP) demonstrated binding of c-Myb to the ,443 OPN promoter region, and binding could significantly be enhanced after bFGF stimulation. Moreover, as shown by electrophoretic mobility shift assays (EMSA), recombinant DNA-binding domain of c-Myb bound in a sequence-specific manner to this region. Finally, the role of c-Myb for OPN gene regulation via binding to the ,443 promoter region could be further substantiated by ectopic overexpression of c-Myb in melanoma cells, using different reporter gene constructs. Taken together, it is demonstrated that the ,443 promoter region exerts influence on OPN gene expression in melanoma cells, and differential binding of c-Myb transcription factor appears to play a major role in this process. These findings might be a feasible explanation for different OPN expression levels in metastatic tumors and may also have prognostic and therapeutic relevance. © 2008 Wiley-Liss, Inc. [source] Histopathological characterization of aortic intimal sarcoma with multiple tumor emboliPATHOLOGY INTERNATIONAL, Issue 11 2000Naoki Nishida A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor. [source] Unbiased selection of bone marrow derived cells as carriers for cancer gene therapyTHE JOURNAL OF GENE MEDICINE, Issue 11 2007Susanne I. Lang Abstract Background There is currently great interest in development of cell-based carriers for delivery of viral vectors to metastatic tumors. To date, several cell carriers have been tested based largely upon their predicted tumor-localizing properties. However, cell types may exist which can be mobilized from the circulation by a tumor which have not yet been identified. Here we use an unbiased screen of bone marrow (BM) cells to identify cells which localize to tumors and which might serve as effective candidate cell carriers without any prior prediction or selection. Methods Unsorted BM cells from green fluorescent protein (GFP)-transgenic donor mice were adoptively transferred into C57Bl/6 mice bearing pre-established subcutaneous B16 melanoma tumors. Forty-eight hours and eight days later, tumors, organs and blood were analyzed for GFP-expressing cells by flow cytometry. The phenotype of GFP cells in organs was determined by co-staining with specific cell surface markers. Results CD45+ hematopoietic cells were readily detected in tumor, spleen, bone marrow, blood and lung at both time points. Within these CD45+ cell populations, preferential accumulation in the tumor was observed of cells expressing Sca-1, c-kit, NK1.1, Thy1.2, CD14, Mac-3 and/or CD11c. Lymphodepletion increased homing to spleen and bone marrow, but not to tumors. Conclusions We have used an in vivo screen to identify populations of BM-derived donor cells which accumulate within tumors. These studies will direct rational selection of specific cell types which can be tested in standardized assays of cell carrier efficiency for the treatment of metastatic tumors. Copyright © 2007 John Wiley & Sons, Ltd. [source] Immunophenotypic Comparison of Salivary Gland Oncocytoma and Metastatic Renal Cell Carcinoma,THE LARYNGOSCOPE, Issue 6 2005John A. Ozolek MD Abstract Objectives/Hypothesis: The differential diagnosis of oncocytic neoplasms of salivary glands includes both primary and metastatic tumors, one of which is renal cell carcinoma. This study compared immunohistochemical staining characteristics of oncocytomas arising from salivary gland to metastatic renal cell carcinoma using a panel of markers. Study Design: Immunohistochemistry for cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen (EMA), vimentin, CD10, and renal cell carcinoma marker (RCC) was performed on 10 oncocytomas and compared with ten metastatic renal cell carcinomas. Results: There were overlapping histologic findings in the oncocytomas and metastatic renal cell carcinomas, with oncocytomas displaying clear cell changes in 2 of 10 cases. CK7 was positive in 9 of 10 oncocytomas and CK20 in 8 of 10 (7/10 stained for both), and vimentin was only weakly positive in 4 of 10 oncocytomas. All oncocytomas were EMA positive, with membranous staining, and all were negative for CD10 and RCC. Metastatic renal cell carcinoma was strongly positive for vimentin, EMA, and CD10 in most cases. RCC and CK7 were variably positive in metastatic renal cell carcinomas (4/10), and only 1 of 10 showed weak staining with CK20. Conclusions: Salivary gland oncocytomas and metastatic renal cell carcinomas share some similar histologic and immunohistochemical characteristics. CD10 and CK20 were the most useful markers to distinguish metastatic renal cell carcinoma from oncocytomas in the salivary gland, whereas RCC, EMA, CK7, and vimentin are not as useful. [source] Molecular characterization of the G,-globin-Tag transgenic mouse model of hormone refractory prostate cancer: Comparison to human prostate cancer,THE PROSTATE, Issue 6 2010Alfonso Calvo Abstract BACKGROUND Prostate cancer (PrCa) has a high incidence in Western countries and at present, there is no cure for hormone refractory prostate cancer. Transgenic mouse models have proven useful for understanding mechanisms of prostate carcinogenesis. The characterization of genetically modified mouse PrCa models using high-throughput genomic analyses provides important information to guide appropriate experiment applications for such model. METHODS We have analyzed the transcriptome of the hormone refractory and highly metastatic Fetal Globin-SV40/T-antigen (G,-globin-Tag) transgenic mouse model for PrCa compared to normal mouse prostate tissue. Gene expression patterns found in G,-globin-Tag mouse prostate tumors were compared with publicly available human localized and metastatic prostate tumors (GEO accession # GSE3325) through hierarchical cluster analysis, Pearson's rank correlation coefficient, and Self Organizing Feature Maps (SOM) analyses. RESULTS G,-globin-Tag tumors clustered closely with human metastatic tumors and gene expression patterns had a significant correlation (P,<,0.01), unlike human localized primary tumors (P,>,0.6). Bioinformatic analyses identified deregulated genetic pathways and networks in G,-globin-Tag tumors, which displayed similarities to alterations in human PrCa. Changes in the expression of genes involved in DNA replication and repair (Rb1, p53, Myc, PCNA, DNMT3A) and growth factor signaling pathways (TGF,2, ERK1/2, NRas, and Notch1) are deregulated in the G,-globin-Tag tumors, suggesting their key role in the oncogenic process. Identification of an enrichment of putative binding sites for transcription factors revealed eight transcription factors that may be important in G,-globin-Tag carcinogenesis, including SP1, NF-Y, CREB, Elk1, and E2F. Novel genes related to microtubule regulation were also identified in G,-globin-Tag tumors as potentially important candidate targets for PrCa. Overexpression of stathmin-1, whose expression was increased in human metastatic prostate tumors, was validated in G,-globin-Tag tumors by immunohistochemistry. This protein belongs to the SV40/T-antigen cancer signature identified in previous studies in prostate, breast, and lung cancer mouse models. CONCLUSIONS Our results show that the G,-globin-Tag model for hormone refractory PrCa shares important features with aggressive, metastatic human PrCa. Given the role of stathmin-1 in the destabilization of microtubles and taxane resistance, the G,-globin-Tag model and other SV40/T-antigen driven transgenic models may be useful for testing potential therapies directed at stathmin-1 in human prostate tumors. Prostate 70: 630,645, 2010. Published 2010 Wiley-Liss, Inc. [source] Glutathione S -transferase pi is upregulated in the stromal compartment of hormone independent prostate cancerTHE PROSTATE, Issue 2 2003Ming Li Abstract Background Glutathione S -transferase (GST) pi is a detoxifying enzyme abundant in normal prostate basal cells but only rarely expressed in prostate cancer cells. The current studies are the first to focus on GST pi in the stromal compartment of prostate tumors. Methods We employed immunohistochemical, immunofluorescence, and Western blot analysis to measure GST pi expression and subcellular localization in 21 primary and metastatic tumors from patients with hormone independent prostate cancer, as well as seven lymph node metastases and six prostatectomy specimens. Results GST pi was detectable in stromal cells in 17 of the 21 hormone independent prostate tumors. GST pi tissue distribution in hormone independent tumors coincided with vimentin staining, suggesting that GST pi is expressed by reactive fibroblasts and/or myofibroblasts. Conclusions The current results suggest that prostate cancer cells induce an injury response in the stroma during progression to hormone independence, which results in GST pi expression. Stromal GST pi may contribute to chemoresistence of advanced prostate cancer. Prostate 56: 98,105, 2003. © 2003 Wiley-Liss, Inc. [source] Adjuvant and neoadjuvant chemotherapy for Ewing sarcoma family tumors in patients aged between 40 and 60,CANCER, Issue 4 2007Report of 35 cases, comparison of results with 586 younger patients treated with the same protocols in the same years Abstract BACKGROUND. The clinical and pathologic features of 46 patients 40 to 60 years old with Ewing sarcoma family tumor (ESFT) diagnosed at the authors' institute between 1972 and 2000 were reviewed. METHODS. Ten patients with metastatic tumors at presentation went elsewhere for treatment; 35 of 36 remaining cases with localized disease were treated at the authors' institution according to different chemotherapy protocols activated in successive years. In patients with nonmetastatic tumors local treatment was surgery in 9 patients, radiotherapy in 16, and surgery followed by radiotherapy in 10. RESULTS. At follow-up times ranging from 6 and 34 years (mean, 17.8 years), 15 patients (42.9%) remained continuously disease-free, 19 experienced recurrence, and 1 died of chemotherapy-related toxicity. The 5- and 10-year event-free survivals were 42.9% and 35.2%, respectively, and the 5- and 10-year overall survivals were 46.1% and 42.8%, respectively. Comparing this group of patients with 586 cases of younger patients seen in the same period at Rizzoli, the only difference between the 2 groups was a significantly higher rate of tumors located in the soft tissues with a larger volume in the older group. The results achieved were comparable in the 2 groups, although the older group had a lower chemotherapy dose-intensity and a higher rate of WHO grade 4 hematologic toxicity. CONCLUSIONS. For patients with localized disease treated with adjuvant and neoadjuvant chemotherapy the results were essentially comparable in the 2 groups. It is concluded that patients 40 years or older with ESFT should be treated in the same way as younger patients and included in treatment trials for these tumors. Cancer 2007. © 2007 American Cancer Society. [source] Dynamic alterations of the extracellular environment of ovarian surface epithelial cells in premalignant transformation, tumorigenicity, and metastasisCANCER, Issue 8 2002Callinice D. Capo-Chichi Ph.D. Abstract BACKGROUND Ovarian surface epithelial cells are positionally organized as a single cell layer by a sheet of basement membrane. It is believed that the contact of the ovarian surface epithelial cells with the basement membrane regulates cell growth and ensures the organization of the epithelium. Disabled-2 (Dab2), a signal transduction protein and a candidate tumor suppressor of ovarian carcinoma, functions in positional organization of ovarian surface epithelial cells. In ovarian carcinomas, genetic and epigenetic changes enable the tumor cells to escape positional control and proliferate in a disorganized fashion. Alterations in the extracellular environment may also be critical for tumor initiation and progression. METHODS We analyzed and compared the presence of collagen IV and laminin, the scaffold proteins of the basement membrane, and Dab2 in 50 ovarian tumors that are restricted to the ovaries and in 50 metastases of ovarian tumors by immunohistochemistry. Expression of collagen IV, laminin, and Dab2 was also analyzed by Northern blotting in a panel of human ovarian surface epithelial and cancer cell lines. RESULTS The basement membrane is often absent in morphologically benign ovarian surface and cyst epithelium and low-grade tumors and collagen IV and laminin are absent in the extracellular matrix of most of the primary tumors tested. Of the 50 ovarian tumors confined to the ovaries, 6% (3 of 50) were collagen IV positive and 24% (12 of 50) were laminin positive tumors. Of the 50 metastatic tumors, 16% (8 of 50) are collagen IV positive and 86% (43 of 50) are laminin positive. In addition, even in the metastatic ovarian tumors that are largely collagen IV negative, there are pockets of local areas in which the tumor cells are surrounded by collagen IV-positive staining. Dab2 is absent in the majority of ovarian tumors found in both ovaries and metastatic sites. In both nontumorigenic human ovarian surface epithelial and cancer cell lines, collagen IV, laminin, and Dab2 are expressed aberrantly. CONCLUSIONS Loss of the basement membrane may be an early event in the preneoplastic transformation of ovarian surface epithelium and in the early stages of tumorigenesis before tumor invasion and metastasis. The majority of primary ovarian tumors examined lack collagen IV and laminin in their extracellular matrix. However, expression of laminin is restored in the majority of metastatic tumors. Reexpression of collagen IV may also contribute to tumor metastasis. The ability of tumor cells to dynamically alter the expression of collagen IV and laminin may facilitate the shedding of cancer cells into the peritoneal spaces and subsequent attachment to the metastatic sites. We propose that loss of collagen IV and laminin may be an initial event in ovarian tumorigenicity and that restoration of collagen IV and laminin expression in the later stages of tumor development may promote metastasis of ovarian tumors. Cancer 2002;95:1802,15. © 2002 American Cancer Society. DOI 10.1002/cncr.10870 [source] Orbital space-occupying lesions in Denmark 1974,,1997ACTA OPHTHALMOLOGICA, Issue 5 2000Sven Johansen ABSTRACT. Purpose: To determine the frequency, distribution according to diagnosis and the recurrence frequency of orbital space-occupying lesions in Denmark, to determine sex and age of the patients and to establish a national orbital data register. Methods: All biopsied/surgically removed orbital lesions collected by Danish pathological departments during the period 1974,1997 were identified by SNOMED codes. In addition, in each case gender and age of the patients and number of recurrences were registered. Results: 965 orbital lesions from 841 patients were identified during the 24-year period. The incidence of orbital lesions increased significantly over the study period and at present about 80 cases/year are registered. The ratio benign/malignant lesion per year remained constant during the observation period. Lesions in children constituted a total of 152 (16%), the percentage of lesions in children being constant during the period. Malignant tumors comprised a total of 364 (45%) in adults and 34 (22%) in children. Malignant tumors were in adults distributed with 43% primary, 48% secondary invading and 9% metastatic tumors, and in children with 65% primary, 29% secondary invading and 6% metastatic tumors. Normal tissue was only found in 6% of the cases recorded. Conclusion: A registration of all histologically evaluated orbital space-occupying lesions in Denmark during a period of 24 years was performed and a national orbital database established. Orbital lesions are rare and primarily benign. [source] Exfoliative sputum cytology of cancers metastatic to the lung,DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005Tehmina Z. Ali M.D. Abstract Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980,2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases. Diagn. Cytopathol. 2005;33:147,151. © 2005 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||