Tumor Grade (tumor + grade)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Tumor Grade

  • high tumor grade


  • Selected Abstracts


    Expression of Integrin ,v,3 in Gliomas Correlates with Tumor Grade and Is not Restricted to Tumor Vasculature

    BRAIN PATHOLOGY, Issue 3 2008
    Oliver Schnell MD
    Abstract In malignant gliomas, the integrin adhesion receptors seem to play a key role for invasive growth and angiogenesis. However, there is still a controversy about the expression and the distribution of ,v,3 integrin caused by malignancy. The aim of our study was to assess the extent and pattern of ,v,3 integrin expression within primary glioblastomas (GBMs) compared with low-grade gliomas (LGGs). Tumor samples were immunostained for the detection of ,v,3 integrin and quantified by an imaging software. The expression of ,v,3 was found to be significantly higher in GBMs than in LGGs, whereby focal strong reactivity was restricted to GBMs only. Subsequent analysis revealed that not only endothelial cells but also, to a large extent, glial tumor cells contribute to the overall amount of ,v,3 integrin in the tumors. To further analyze the integrin subunits, Western blots from histologic sections were performed, which demonstrated a significant difference in the expression of the ,3 integrin subunit between GBMs and LGGs. The presented data lead to new insights in the pattern of ,v,3 integrin in gliomas and are of relevance for the inhibition of ,v,3 integrin with specific RGD peptides and interfering drugs to reduce angiogenesis and tumor growth. [source]


    Chromosome 9p deletions identify an aggressive phenotype of clear cell renal cell carcinoma

    CANCER, Issue 20 2010
    Jeffrey La Rochelle MD
    Abstract BACKGROUND: The authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS) and whether it was associated with more aggressive behavior in small renal masses. METHODS: In total, 703 ccRCC tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). Tumor grade, classification, and size; 9p status; Eastern Cooperative Oncology Group performance status (ECOG PS); lymph node involvement; and the presence of metastasis were recorded. Outcomes were stratified by 9p status, and a Cox proportional hazards models was constructed using TNM staging, ECOG PS, tumor size, tumor grade, and 9p status. RESULTS: Deletions of 9p were detected in 97 tumors (13.8%). At presentation, 9p-deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (T) classification (T3-T4), and to have lymph node or distant metastases (P < .01). The median DSS for patients with and without 9p deletions was 37 months and 82 months, respectively (P < .01). In patients with localized disease, the median RFS in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (P < .01). In patients who had localized lesions that measured ,4 cm in greatest dimension, 9p-deleted tumors were more likely to recur (19% vs 2%; P = .01). CONCLUSIONS: Deletion of chromosome 9p in ccRCC occurred in 14% of patients and was associated with higher grade and T classification, and the presence of lymph node and distant metastases. In addition, 9p deletion independently conferred a worse prognosis for patients with localized ccRCC, and most noteworthy, in patients with localized, small renal masses. Preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment. Cancer 2010. © 2010 American Cancer Society. [source]


    Breast carcinoma in men

    CANCER, Issue 1 2004
    A population-based study
    Abstract BACKGROUND Male breast carcinoma is an uncommon disease, and most previous studies have been single-institution series that were limited by extremely small sample sizes. The goals of the current study were to fill in the major gaps in knowledge regarding the incidence, presenting characteristics, prognostic factors, and survival rates of male breast carcinoma and to determine how breast carcinoma differs between men and women. METHODS Data from the National Cancer Institute Surveillance, Epidemiology, and End Results 1973,1998 database were used. Age-adjusted incidence rates were calculated. Characteristics of the patients and presenting tumors were compared between men and women. Univariate and multivariate analyses were performed to determine the effect of each variable on overall survival. Survival rates by disease stage were compared for men and women. RESULTS Over the years of the study, the incidence of male breast carcinoma increased significantly from 0.86 to 1.08 per 100,000 population (P < 0.001). Men had a higher median age at diagnosis (P < 0.001) and were more likely to have lymph node involvement (P < 0.001), a more advanced stage at diagnosis (P < 0.001), and tumors that were positive for estrogen receptor (ER) (P < 0.001) and progesterone receptor (PR) (P < 0.001). In multivariate analysis, larger tumor size and lymph node involvement were associated with shortened survival. Tumor grade and ER/PR status did not appear to independently influence survival. Relative survival rates by stage of disease for men and women were similar. CONCLUSIONS Although it remains a rare disease, the incidence of male breast carcinoma is increasing. Breast carcinoma in men has some epidemiologic and biologic differences from breast carcinoma in women. Cancer 2004. © 2004 American Cancer Society. [source]


    MRI tumor characterization using Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine MÔ), a protein-avid contrast agent

    CONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2006
    Hans-Jürgen Raatschen
    Abstract The rationale and objectives were to define the MRI tumor-characterizing potential of a new protein-avid contrast agent, Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate (Gadofluorine MÔ; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05,mmol,Gd,kg,1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N -ethyl- N -nitrosourea (ENU), 45,250,mg,kg,1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two-compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (KPS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff,Bloom,Richardson score) and location of necrosis. Eighteen tumor-bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. KPS and fEV*, but not fPV obtained from tumors correlated significantly (p,<,0.05) with the SBR tumor grade, r,=,0.65 and 0.56, respectively. Estimates for KPS and fEV* but not fPV were significantly lower in a group consisting of benign and low-grade malignant tumors compared with the group of less-differentiated high-grade tumors (1.61,±,0.64 vs 3.37,±,1.49, p,<,0.01; 0.45,±,0.17 vs 0.78,±,0.24, p,<,0.01; and 0.076,±,0.048 vs 0.121,±,0.088, p,=,0.24, respectively). It is concluded that the protein-avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low-grade malignant lesions from high-grade cancers. Copyright © 2006 John Wiley & Sons, Ltd. [source]


    Hypoxia-inducible factor-1, blocks differentiation of malignant gliomas

    FEBS JOURNAL, Issue 24 2009
    Huimin Lu
    Aberrant differentiation is a characteristic feature of neoplastic transformation, while hypoxia in solid tumors is believed to be linked to aggressive behavior and poor prognosis. However, the possible relationship between hypoxia and differentiation in malignancies remains poorly defined. Here we show that rat C6 and primary human malignant glioma cells can be induced to differentiate into astrocytes by the well-known adenylate cyclase activator forskolin. However, hypoxia-inducible factor-1, expression stimulated by the hypoxia mimetics cobalt chloride or deferoxamine blocks this differentiation and this effectiveness is reversible upon withdrawal of the hypoxia mimetics. Importantly, knockdown of hypoxia inducible factor-1, by RNA interference restores the differentiation capabilities of the cells, even in the presence of cobalt chloride, whereas stabilization of hypoxia-inducible factor-1, through retarded ubiquitination by von Hippel-Lindau tumor suppressor gene silence abrogates the induced differentiation. Moreover, targeting of HIF-1 using chetomin, a disrupter of HIF-1 binding to its transcriptional co-activator CREB-binding protein (CBP)/p300, abolishes the differentiation-inhibitory effect of hypoxia-inducible factor-1,. Administration of chetomin in combination with forskolin significantly suppresses malignant glioma growth in an in vivo xenograft model. Analysis of 95 human glioma tissues revealed an increase of hypoxia-inducible factor-1, protein expression with progressing tumor grade. Taken together, these findings suggest a key signal transduction pathway involving hypoxia-inducible factor-1, that contributes to a differentiation defect in malignant gliomas and sheds new light on the differentiation therapy of solid tumors by targeting hypoxia-inducible factor-1,. Structured digital abstract ,,MINT-7292117: CBP (uniprotkb:Q6JHU9) physically interacts (MI:0915) with Hif1a (uniprotkb:O35800) by anti bait coimmunoprecipitation (MI:0006) [source]


    Mucoepidermoid carcinoma of Stensen's duct: A case report and review of the literature

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2005
    Roland Giger MD
    Abstract Background. Mucoepidermoid carcinoma of Stensen's duct is a rare neoplasm, with only five cases reported in the literature. Methods. We report another case of mucoepidermoid carcinoma of Stensen's duct and review the literature. Results. Stensen's duct neoplasms tend to be symptomatic at an early stage by causing an obstruction of the parotid duct. New imaging techniques such as MR sialography and sialoendoscopy are very helpful in diagnosis and patient management. Conclusions. Although the rarity of this condition prevents definitive conclusions about the optimal treatment, we propose that Stensen's duct neoplasms should be treated like similar neoplasms occurring in the parotid gland tissue, taking into consideration clinical stage, tumor grade, and surgical margins. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source]


    High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican population

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2004
    Adriana Báez PhD
    Abstract Background. Recent evidence has accumulated suggesting that human papillomavirus (HPV) plays a role in the development of head and neck squamous cell carcinoma (HNSCC). HPV16 is the most common of the HPV subtypes associated with oral and laryngeal malignancies. This study estimated the prevalence of HPV16 DNA in Puerto Rican patients with HNSCC. Methods. DNA was extracted from frozen tissue of 118 HNSCCs. Genomic DNA was screened for the presence of HPV16 DNA with E6-specific and E7-specific primers. Results. HPV16 was detected in tumor tissue of 52 patients (44%) with HNSCC. The oropharynx had a slightly higher incidence of HPV16 DNA. Fifteen of 66 patients with HPV16-negative HNSCC later had recurrences. Positivity for HPV16 was independent of the tumor grade, tumor stage, nodal status, and tobacco or alcohol use. The 3-year survival rate was higher in HPV16-positive patients than in HPV16-negative patients (36% vs 21%). Conclusions. Our findings suggest that HPV16 may play a role in the etiology of a subgroup of HNSCC in Puerto Ricans. Overall survival times of the HPV16-positive patients were not significantly different from those of HPV16-negative patients. Increasing our understanding of the role of HPV16 in the etiology of HNSCC might facilitate the development of new treatment modalities for this subgroup of HNSCC. © 2004 Wiley Periodicals, Inc. Head Neck26: 778,784, 2004 [source]


    Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2010
    Niamh C. Murphy
    Abstract The phospholipid transfer protein STARD10 cooperates with c-erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome. The central findings were independently validated by immunohistochemistry in a retrospective cohort of 222 patients with breast cancer with a median follow-up of 64 months. Kaplan,Meier and Cox proportional hazards analyses were used for univariate and multivariate analyses. Patients with low STARD10 or high HER2 tumor mRNA levels formed discrete groups each associated with a poor disease-specific survival (p = 0.0001 and p = 0.0058, respectively). In the immunohistochemical study low/absent STARD10 expression i.e. ,10% positive cells was observed in 24 of 222 (11%) tumors. In a univariate model, low/absent STARD10 expression was significantly associated with decreased patient survival (p = 0.0008). In multivariate analyses incorporating tumor size, tumor grade, lymph node status, ER, PR and HER2 status, low STARD10 expression was an independent predictor of death from breast cancer (HR: 2.56 (95% CI: 1.27,5.18), p = 0.0086). Furthermore, low/absent STARD10 expression, HER2 amplification and triple negative status were independent prognostic variables. Loss of STARD10 expression may provide an additional marker of poor outcome in breast cancer identifying a subgroup of patients with a particularly adverse prognosis, which is independent of HER2 amplification and the triple negative phenotype. [source]


    Prognosis of adenocarcinoma of the uterine cervix: p53 expression correlates with higher incidence of mortality

    INTERNATIONAL JOURNAL OF CANCER, Issue 1 2007
    Astrid Baalbergen
    Abstract We investigated the significance of prognostic markers-estrogen receptor, progesterone receptor, p53, MIB-1 and bcl-2 - in adenocarcinoma of the uterine cervix. In 101 patients with primary cervical adenocarcinoma, treated from 1989 to 2000, we evaluated clinical parameters in relation to these prognostic markers. Mean age of patients was 45 years. Seventy eight percent of the patients were in FIGO stage I, 16% stage II, 7% stage III and IV. estrogen receptor, progesterone receptor, p53 and bcl-2 immunoreactivity was scored as 0 (up to 5% positive cells), 1+ (5,25% of cells positive), 2+ (26,50% of cells positive), 3+ (51,75% of cells positive) or 4+ (>76% of cells positive). MIB-1 was scored in 10 categories: 0,10, 11,20, 21,30, 31,40, 41,50, 51,60, 61,70, 71,80, 81,90, 91,100. The overall survival rate was 67%. Survival was not influenced by estrogen receptor, progesterone receptor, MIB-1, or bcl-2 strongly positive staining. Only p53 showed significant influence on survival, even when adjusted for stage or tumor grade. In conclusion, it does not seems useful to determine estrogen receptor, progesterone receptor, MIB-1 or bcl-2 in cervical adenocarcinomas as an indication of prognosis: survival is not influenced by presence or absence. However, if p53 staining is strongly positive survival is significantly worse than in tumors scored as negative or weak positive. © 2007 Wiley-Liss, Inc. [source]


    Expression of HYAL2 mRNA, hyaluronan and hyaluronidase in B-cell non-Hodgkin lymphoma: Relationship with tumor aggressiveness

    INTERNATIONAL JOURNAL OF CANCER, Issue 2 2005
    Philippe Bertrand
    Abstract Hyaluronidases and their substrate, hyaluronan (HA), were mainly explored in solid tumors but rarely in hematologic malignancies. While HA involvement was demonstrated in invasion and metastasis in most cases of solid tumors, the role of hyaluronidases in cancer progression remains controversial. One of the hyaluronidases, HYAL2, is suspected to be involved in the first step of HA degradation. In this work, HYAL2 mRNA, HA and total hyaluronidases expression were examined in lymphoma tissue extracts and correlated to the lymphoma subtype. Real-time RT-PCR was performed to evaluate HYAL2 mRNA. HA and hyaluronidase were assayed by enzyme-linked sorbent assay. Our results showed that HYAL2 mRNA expression was correlated to lymphoma diagnosis (p = 6 × 10,3) and was significantly lower in high-grade lymphoma, i.e., diffuse large B-cell diffuse lymphomas (DLBCLs). Several forms of hyaluronidase were detected by zymography and total hyaluronidase activity detected in tissue extracts was not significantly different according to tumor grade. HA levels also correlated to lymphoma subtype (p = 1 × 10,5) and were higher in DLBCLs. Moreover, HYAL2 mRNA and HA expressions were inversely correlated (p = 0.035). HYAL2 gene is localized on chromosome 3p21, which contains candidates tumor suppressor genes. Our results suggest that HYAL2 may have a prognostic significance in lymphomas and an antioncogenic activity. Conversely, HA overexpression in high-grade lymphomas is in favor of its involvement in tumor development and could provide a useful target for lymphoma therapy using HA-binding peptides. [source]


    Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2007
    Tomoaki Terakawa
    Background: The objective of this study was to evaluate the clinical outcome after surgical management of renal cell carcinoma (RCC) extending to the inferior vena cava (IVC). Methods: This study included a total of 55 patients (41 men and 14 women; mean age, 59.3 years) with RCC (39 right- and 16 left-sided tumors) involving the IVC, who underwent radical nephrectomy and tumor thrombectomy between 1983 and 2005 at a single institution in Japan. The level of thrombus was classified as follows: level I, infrahepatic; level II, intrahepatic; level III, suprahepatic; and level IV, extending to the atrium. Clinicopathological data from these patients were retrospectively reviewed to identify factors associated with survival. Results: There were 11 and 18 patients who were diagnosed as having lymph node and distant metastases, respectively. Twenty-two patients had tumor thrombus in level I, 20 in level II, 10 in level III, and 3 in level IV. Pathological examinations demonstrated that 34 and 21 patients had clear cell carcinoma and non-clear cell carcinoma, respectively, 42, 9 and 4 were pT3b, pT3c and pT4, respectively, and 6, 35 and 14 were Grades 1, 2 and 3, respectively. Cancer-specific 1-, 3- and 5-year survival rates of these 55 patients were 74.5%, 51.4% and 30.3%, respectively. Among several factors examined, clinical stage (P = 0.047), lymph node metastasis (P = 0.016), histological subtype (P = 0.034) and tumor grade (P < 0.001) were significantly associated with cancer-specific survival by univariate analysis. Furthermore, multivariate analysis demonstrated clinical stage (P = 0.037) and tumor grade (P < 0.001) as independent predictors of cancer-specific survival irrespective of other significant factors identified by univariate analysis. Conclusions: In patients with RCC involving the IVC, biological aggressiveness characterized by tumor grade rather than tumor extension would have more potential prognostic importance; therefore, more intensive multimodal therapy should be considered in patients with high grade RCC with tumor thrombus extending into the IVC. [source]


    Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004
    TETSUYA 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]


    Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgery

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2004
    TAKESHI ISHIMURA
    Abstract Background: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. Methods: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6,162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. Results: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. Conclusion: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease. [source]


    Clinicopathological factors predicting recurrence of N0M0 renal cell carcinoma: A case series analysis of one facility

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2003
    AIICHIRO MASUDA
    Abstract Background: Although many factors have been reported as predictors of the recurrence of renal cell carcinoma (RCC), none of the factors are consistent among different studies. In the study presented here, the potential clinicopathological predictors of the recurrence of N0M0 RCC were examined. Methods: A total of 201 patients who underwent nephrectomy for N0M0 RCC were examined to determine the pathological tumor stage (pT stage), pathological tumor grade of malignancy (tumor grade), symptoms, and tumor size. Results RCC recurred in 29 patients (14.4%), 50% of whom developed new tumors within 24 months after nephrectomy. The disease-free 3- and 10-year survival rates declined as the pT stage and tumor grade increased: these rates were, respectively, 98.6% and 86.5% for pT1a; 93.7% and 87.9% for pT1b; 100% and 100% for pT2; 78.6% and 58.0% for pT3a; and 88.9% and 16.7% for pT3b. Significant differences in the recurrence rate were noted between pT3 and pT1 or pT2, as well as between grade 3 disease and grade 1 or grade 2 tumors. Multivariate analysis showed that a combination of the pT stage, grade, and presence of symptoms was useful for predicting the recurrence of RCC. Conclusion: The present study showed that patients undergoing nephrectomy for N0M0 RCC should be followed-up carefully for 2 years postoperatively with special attention to high pT stage, high grade, and the development of symptoms. [source]


    Prognostic significance of tumor grade for renal cell carcinoma

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2000
    Yasutada Onodera
    Abstract Background: The natural history and prognosis of renal cell carcinoma cannot be predicted. Based on the Japanese classification system, the value of nuclear grade were assessed as a possible prognostic factor for renal cell carcinomas. Methods: In this retrospective study of 116 patients with renal cell carcinoma, radical nephrectomy was performed. Survival rates were calculated using the Kaplan,Meier method and multivariate analysis was performed using Cox's proportional hazard model. Results: Distribution by stage and grade in the population of renal cell carcinomas was as follows: pT1 in 13 cases (11.3%), pT2 in 65 cases (56.5%), pT3 in 36 cases (31.3%) and pT4 in one case (0. 9%) and grade 1, 28 (24.1%), grade 2, 69 (59.5%) and grade 3, 16 (13.8%). Three cases could not be determined because of pre-operative embolization of the renal cell carcinomas. Nuclear grade was correlated with stage (P = 0.0002), the presence of perirenal fat involvement (P = 0.003) and metastases (P = 0.007). A significant difference in survival was found between grades 1 and 3 (P = 0.0001) and grades 2 and 3 (P = 0.0001), respectively. Survival was significantly correlated with sex (P = 0.0125), tumor size (P = 0.0001), the presence of lymph node metastasis (P = 0.0001), renal vein involvement (P = 0.0001), perirenal fat involvement (P = 0.002) or distant metastasis (P = 0.0001). The multivariate analysis showed that the occurrence of tumor grade (P = 0.0006) or distant metastasis were independent prognostic values. Conclusion: The observations lead us to conclude that the nuclear grade according to the Japanese classification system appears to be of reliable prognostic value for renal cell carcinomas. [source]


    Rcl is a novel ETV1/ER81 target gene upregulated in breast tumors

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2008
    Sook Shin
    Abstract ETV1 (ER81) is a transcription factor that can be activated by HER2/Neu, a proto-oncoprotein often overexpressed in metastatic breast tumors. Here, we demonstrate that ETV1 downregulation suppresses proliferation of HER2/Neu-positive MDA-MB-231 breast cancer cells in vitro and tumor formation in vivo, proving for the first time the existence of a critical role of ETV1 in breast cancer cell physiology. A screen for novel ETV1 target genes hinted at Rcl, an enzyme involved in nucleotide metabolism. To characterize the human Rcl gene, we cloned its promoter and found that ETV1 and HER2/Neu cooperated in activating the Rcl promoter, whereas a dominant-negative ETV1 molecule suppressed the Rcl promoter. Moreover, ETV1 and HER2/Neu synergized to upregulate the endogenous Rcl gene. ETV1 also bound to the Rcl promoter in vivo, indicating that Rcl is a bona fide target gene of ETV1. Hybridization of Rcl cDNA to a breast cancer array revealed that Rcl is overexpressed in ,40% of all breast tumors. Importantly, its expression significantly escalates with increasing tumor grade, strongly implicating that Rcl contributes to breast tumorigenesis. Since joint overexpression of Rcl with vascular endothelial growth factor, another target gene of ETV1, has been shown to induce tumor formation, Rcl may be one crucial effector of ETV1 and HER2/Neu in breast tumors. Furthermore, given its expression pattern and enzymatic function in nucleotide metabolism, Rcl presents itself as a novel target in breast cancer therapy via modulation of its activity by small molecule drugs. J. Cell. Biochem. 105: 866,874, 2008. © 2008 Wiley-Liss, Inc. [source]


    Expression of vascular endothelial growth factor in renal cell carcinoma is correlated with cancer advancement

    JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2003
    Ching-Chiang Yang
    Abstract Vascular endothelial growth factor (VEGF) functions as a regulator of neovascularization in malignant cells. VEGF as a mitogen is thought to alter renal cell carcinoma formation and tumor progression. We investigated the expression of the VEGF gene in order to evaluate its clinical significance in renal cell carcinoma. Tissue samples from 198 patients with renal cell carcinoma were examined with an immunohistochemical stain for the expression of the VEGF gene. The expression rate was compared to 34 normal renal cortical samples obtained from renal surgery from noncancer patients. There were significant differences between normal renal cortex (0%) and cancer tissue (54.5%) in positive staining of VEGF protein (P<0.001). With the progression of tumor grade, the positive rate of VEGF gene expression significantly increased. The expression rate of the VEGF gene in the advanced group, such as with lymph node involvement or vein invasion, was greater than that in the locally confined group (P<0.001). The results revealed that expression of the VEGF gene is proportional to the formation and progression of renal cell carcinoma, which may allow VEGF to be used as a prognostic marker for renal cell carcinoma. J. Clin. Lab. Anal. 17:85,89, 2003. © 2003 Wiley-Liss, Inc. [source]


    CK7 expression in primary cutaneous squamous cell carcinoma

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2010
    Melissa Pulitzer
    Aim: To evaluate cytokeratin 7 (CK7) immunoreactivity in invasive primary cutaneous squamous cell carcinomas (SCCs). Methods: Twenty-seven primary cutaneous SCCs from 25 patients were evaluated for tumor grade using hematoxylin and eosin-stained slides and for percentage and intensity of immunoreactivity for CK7. All cases exhibited features of SCC with an in situ component. No glandular or tubular differentiation was present. Staining intensity was graded on a scale of 0,3, with 0 indicating no reaction. Of immunoreactive cases, percentage of tumor staining and distribution of immunoreactivity was documented. Results: Six of 27 SCCs (22%) exhibited immunostaining for CK7. Of those cases, three were poorly differentiated, exhibiting 2 to 3+ intensity in 5,15% of cells. Two were poorly differentiated, with 2 to 3+ intensity in 30,60% of cells. The remaining immunoreactive tumor was moderately differentiated, with 1+ intensity and 5% staining in an area of microinvasion. Conclusion: A subset of cutaneous SCCs, in particular, poorly differentiated tumors, may show focal-to-partial immunoreactivity for CK7. This is important to bear in mind when immunohistochemistry is used to distinguish SCC from simulants, such as porocarcinoma, or other adnexal carcinomas with squamous metaplasia. Pulitzer M, Desman G, Busam KJ. CK7 expression in primary cutaneous squamous cell carcinoma. [source]


    Superficial leiomyosarcoma: a clinicopathologic review and update

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2010
    Clarissa T. Fauth
    Fauth CT, Bruecks AK, Temple W, Arlette JP, DiFrancesco LM. Superficial leiomyosarcoma: a clinicopathologic review and update. Background: Superficial leiomyosarcomas (SLMSs) are rare soft tissue malignancies. A clinicopathologic review of 25 cases was undertaken. Methods: Twenty-five cases diagnosed between 1990 and 2007 were reviewed. Clinical information was obtained from patient charts. Histologic slides were reviewed, and immunohistochemical stains were performed. Results: All patients presented with a nodule. Fourteen tumors were confined to the dermis and 11 involved subcutaneous tissue. Smooth muscle markers were positive in all cases. CD117 was consistently negative. Novel histological features included epidermal hyperplasia, sclerotic collagen bands and increasing tumor grade with the depth of the lesion. Poor outcome was associated with size > 2 cm, high grade and depth of the lesion. Conclusions: SLMSs are rare but important smooth muscle tumors of the skin. The clinical presentation may be non-specific. The histologic appearance is that of a smooth muscle lesion, but epidermal hyperplasia and thickened collagen bands are previously underrecognized features. Immunohistochemical stains are useful in confirming smooth muscle differentiation, but CD117 is of limited utility. SLMS can appear low grade or even benign on superficial biopsies, leading to undergrading or a delay in the correct diagnosis. Clinicians and pathologists alike should therefore be aware of these pitfalls and must approach these cases with caution. [source]


    Immunohistochemical determination of the P15INK4b protein expression in cutaneous squamous cell carcinoma

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2009
    Ahmed I. Moad
    The tumor suppressor gene p15INK4b is a cyclin-dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor-derived cell lines. The precise role of p15INK4b protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15INK4b gene. This study is a continuation of our previous study and aims to determine the possible role of p15INK4b protein expression in the genesis of cutaneous SCC. P15INK4b protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15INK4b was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15INK4b protein expression. The absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. [source]


    Significance of cell kinetic parameters in the prognosis of malignant melanoma: a review

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2 2007
    Pierre Vereecken
    The maximum tumor thickness as measured by Breslow's method is the cornerstone prognostic criterion, but despite this, evolution of the disease in some patients remains unpredictable, confirming that new reliable prognostic factors are awaited. Cell kinetic evaluation has been shown to be a useful tool for assessing the prognosis of breast and gastrointestinal cancer patients. Indeed, in these fields, the mitotic index and MIB-1 expression index, which are indirect estimates of the growth fraction of tumor cell population, are commonly shown to correlate with tumor grade and patient survival and presented as prognostic factors. In melanoma, results of cell kinetic investigations are conflicting: some studies have established a link between high proliferative activity and a bad prognosis, whereas other reports suggest the opposite. The aim of this review is to discuss these findings. [source]


    Debulking surgery for incompletely operated advanced epithelial ovarian carcinoma

    JOURNAL OF SURGICAL ONCOLOGY, Issue 3 2009
    Murat Gultekin MD
    Abstract Background and Objectives There is still no any data about the role of re-operation and re-debulking in previously incompletely operated advanced staged patients with epithelial ovarian carcinoma (EOC). In this study, the authors aimed to analyze the effect of an incomplete primary surgery on patient prognosis. Methods Clinicopathological variables of 317 advanced staged EOC patients were retrospectively collected. Results Twenty-nine patients had an initial incomplete surgery and referred to our center for debulking while remaining 288 had undergone primary debulking surgery at our institution. Comparison of the two groups with respect to clinicopathological variables could not reveal significant difference. Median survival was 3.24 years for re-operated patients while it was 2.07 years for patients who had undergone primary debulking surgery. Upon multivariate analysis, final optimal debulking, tumor grade and a history of an incomplete surgery before the final debulking were the significant prognosticators. A subgroup analysis of re-staged patients could not reveal a significant role for either the type or the time interval between the operations. Conclusion A history of an incomplete primary surgery does not seem to adversely affect patient prognosis and the optimal cytoreductive success achieved in final debulking surgery is still the most important prognostic factor. J. Surg. Oncol. 2009;100:258,260. © 2009 Wiley-Liss, Inc. [source]


    Magnetic Resonance Imaging and Histological Classification of Intracranial Meningiomas in 112 Dogs

    JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2008
    B.K. Sturges
    Background: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. Hypothesis: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. Animals: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. Methods: Retrospective observational study. Results: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. Conclusions and Clinical Importance: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas. [source]


    Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells

    NMR IN BIOMEDICINE, Issue 6 2010
    Tariq Shah
    Abstract A direct correlation exists between increased choline kinase (Chk) expression, and the resulting increase of phosphocholine levels, and histological tumor grade. To better understand the function of Chk and choline phospholipid metabolism in breast cancer we have stably overexpressed one of the two isoforms of Chk-, known to be upregulated in malignant cells, in non-invasive MCF-7 human breast cancer cells. Dynamic tracking of cell invasion and cell metabolism were studied with a magnetic resonance (MR) compatible cell perfusion assay. The MR based invasion assay demonstrated that MCF-7 cells overexpressing Chk-, (MCF-7-Chk) exhibited an increase of invasion relative to control MCF-7 cells (0.84 vs 0.3). Proton MR spectroscopy studies showed significantly higher phosphocholine and elevated triglyceride signals in Chk overexpressing clones compared to control cells. A test of drug resistance in MCF-7-Chk cells revealed that these cells had an increased resistance to 5-fluorouracil and higher expression of thymidylate synthase compared to control MCF-7 cells. To further characterize increased drug resistance in these cells, we performed rhodamine-123 efflux studies to evaluate drug efflux pumps. MCF-7-Chk cells effluxed twice as much rhodamine-123 compared to MCF-7 cells. Chk-, overexpression resulted in MCF-7 human breast cancer cells acquiring an increasingly aggressive phenotype, supporting the role of Chk-, in mediating invasion and drug resistance, and the use of phosphocholine as a biomarker of aggressive breast cancers. Copyright © 2010 John Wiley & Sons, Ltd. [source]


    Assessment of blood volume, vessel size, and the expression of angiogenic factors in two rat glioma models: a longitudinal in vivo and ex vivo study

    NMR IN BIOMEDICINE, Issue 10 2008
    Samuel Valable
    Abstract Assessment of angiogenesis may help to determine tumor grade and therapy follow-up. In vivo imaging methods for non-invasively monitoring microvasculature evolution are therefore of major interest for tumor management. MRI evaluation of blood volume fraction (BVf) and vessel size index (VSI) was applied to assess the evolution of tumor microvasculature in two rat models of glioma (C6 and RG2). The results show that repeated MRI of BVf and VSI , which involves repeated injection of an iron-based MR contrast agent , does not affect either the physiological status of the animals or the accuracy of the MR estimates of the microvascular parameters. The MR measurements were found to correlate well with those obtained from histology. They indicate that microvascular evolution differs significantly between the two glioma models, in good agreement with expression of angiogenic factors (vascular endothelial growth factor, angiopoietin-2) and with activities of matrix metalloproteinases, also assessed in this study. These MRI methods thus provide considerable potential for assessing the response of gliomas to anti-angiogenic and anti-vascular agents, in preclinical studies as well as in the clinic. Furthermore, as differences between the fate of tumor microvasculature may underlie differences in therapeutic response, there is a need for preclinical study of several tumor models. Copyright © 2008 John Wiley & Sons, Ltd. [source]


    Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: Relevance of cellularity and p27Kip1

    PATHOLOGY INTERNATIONAL, Issue 12 2006
    Yuta Nemoto
    The aim of the present study was to determine whether expression of molecules associated with cell cycle regulation and apoptosis might reflect tumor grade and patients' prognosis of gastrointestinal stromal tumor (GIST). Forty-nine cases of gastric GIST were divided into three grades; low, intermediate, and high risk. Ki-67, cyclin A, cyclin D1, cyclin E, p16Ink4, p21Waf1, p27Kip1, cyclin-dependent kinase (cdk)2, cdk4 and single-strand DNA (ssDNA) were immunohistochemically stained and assessed. Ki-67, ssDNA, cyclin A and cdk2 had higher labeling indices (LI) in high-risk than in low-risk cases. Cyclin E expression was greater in the intermediate- than in the low-risk grade. On Kaplan,Meier analysis, tumor size, necrosis, cellularity, Ki-67, ssDNA, and cyclin A LI were significantly correlated with disease-free survival. Necrosis, cellularity, and Ki-67 LI were significant as prognostic factors on univariate, and Ki-67 LI on multivariate Cox hazard tests. Within the high-risk grade, high cellularity and low p27Kip1 subgroups had the worst prognosis. The histological grade is related to cell turnover, assessed in terms of Ki-67, ssDNA, cyclin A, cyclin E, and cdk2 levels. Ki-67, ssDNA, and cyclin A are useful for prediction of prognosis, with cellularity and p27Kip1 expression as further prognostic factors in high-risk cases. [source]


    Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms

    PATHOLOGY INTERNATIONAL, Issue 2 2006
    Eun Yoon Cho
    To clarify possible roles of adhesion molecules including E-cadherin, ,- and ,-catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95 malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly reduced expression of E-cadherin, and overexpression of CD44s, CD56, and CD99 were more frequently observed in adenocarcinomas than in benign and borderline tumors. Expression of CD44v6 and nuclear ,- and ,-catenin were detected only in borderline tumors and adenocarcinomas. Reduced expression of E-cadherin was also correlated with high tumor grade (P = 0.03), presence of peritoneal seeding (P = 0.03), and low overall survival rate (P = 0.02). Overexpression of CD44s was significantly associated with high tumor grade (P = 0.04), advanced stage (P = 0.03), and low overall survival rate (P = 0.02). CD56 was increasingly expressed in the case of advanced stage (P = 0.005) and peritoneal seeding (P = 0.001). Nuclear staining for ,-catenin was correlated with tumor progression (P = 0.004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.02). Only CD44s expression and stage were correlated with overall survival in multivariate study. These results suggest that although E-cadherin, CD44s, CD56, and nuclear ,-catenin immunoexpression seem to be useful prognostic markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are independent prognostic factors. [source]


    Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutations

    PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2006
    Hyun Ju Kang
    Abstract Most gastrointestinal stromal tumors (GIST) have activating mutations in either KIT or PDGFRA. However, a small subset of GIST lacks either mutation. To investigate the molecular characteristics of GIST according to mutation type, protein expression profiles in 12 GIST (2 cases with PDGFRA mutations, 8 cases with KIT mutations and 2 cases lacking either mutation) were analyzed using 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns using 2-DE showed that 15 proteins were differently expressed according to the mutation status. Expression levels of septin and heat shock protein (HSP) 27 were increased in GIST with KIT mutations and annexin V was overexpressed in GIST lacking either mutation. Among the 15 proteins, overexpression of 5 proteins [annexin V, high mobility group protein 1 (HMGB1), C13orf2, glutamate dehydrogenase 1 and fibrinogen beta chain] and decreased expression of RoXaN correlated with a higher tumor grade. These findings suggest that differential protein expression can be used as a diagnostic biomarker. Moreover, it may play a role in the development and progression of GIST according to activating mutation type, as these proteins have been shown to be involved in tumor metastasis, apoptosis and immune response. [source]


    A Decision Tool for Predicting Sentinel Node Accuracy from Breast Tumor Size and Grade

    THE BREAST JOURNAL, Issue 6 2007
    FRCS (Gen. Surg.), Nathan Coombs BSc
    Abstract:, The ability to predict axillary lymph node involvement in breast cancer patients in the preoperative setting is invaluable. This study provides a simple set of formulae to enable clinicians to make informed decisions in the management of screen-detected breast cancer. The tumor pathology reports were obtained of all 4,585 women identified between 1996 and 1999 in New South Wales (NSW) with T1 or T2 breast cancer by the statewide co-ordinated breast screening service (BreastScreen NSW). Equations predicting node positivity were calculated by linear regression analysis and, from published sentinel node false-negative rates, the probability of retrieval of a false-negative axillary lymph node by sentinel node biopsy was calculated for tumors of different size and grade. Node involvement was identified in 1,089 (23.8%) of women. A linear relationship for tumor size, grade, and nodal involvement was predicted by: frequency (%) = 1.5 × tumor size (mm) + 2 (or 6 or 10) for grade I (or II or III) tumors. Assuming a 7.5% false-negative rate, the probability of retrieving a false-negative sentinel node ranged from 0.8% for a patient with a 5 mm, grade I carcinoma to 6.0% for a 50 mm, grade III tumor. These simple formulae are easy to use in a clinical setting. The reference table enables breast surgeons to inform a patient about the absolute probability of false-negative sentinel biopsy rates for patients with screen-detected carcinomas when size can be estimated from preoperative imaging and when tumor grade is often available from preoperative core biopsy. Patients with large, T2 breast tumors may be best treated with axillary dissection rather than sentinel node biopsy alone due to the risk of under-staging the woman's disease and also the high probability of finding a positive sentinel node. [source]


    Correlation of Her-2/neu Gene Amplification with Other Prognostic and Predictive Factors in Female Breast Carcinoma

    THE BREAST JOURNAL, Issue 4 2005
    Reshma Ariga MD
    Abstract: , The purpose of this study was to determine if any relationship exists between Her-2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB-1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her-2/neu amplification by fluorescence in-situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB-1, grade, size and age at diagnosis. Chi-square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her-2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her-2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB-1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her-2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi-square test revealed statistically significant correlation between Her-2/neu amplification and ductal versus lobular carcinoma (p < 0.0003), ER (p = 0.0001) and PR (p < 0.0001) negative tumors, over-expression of MIB-1 (p < 0.0005) and high tumor grade (p = 0.0009), while size of the tumor (p = 0.08) and age of the patients (p = 0.67) were not statistically significant. Correlation was found between Her-2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB-1 index. No correlation was found between size of the tumor and age of the patient with Her-2/neu amplification. [source]