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Lymphatic Metastasis (lymphatic + metastasis)
Selected AbstractsHead and neck mucosal melanoma: Experience with 42 patients, with emphasis on the role of postoperative radiotherapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008Marco Meleti DDS Abstract Background. Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established. Methods. The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported. Results. Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies. Conclusions. The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [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] DNA demethylation of vascular endothelial growth factor-C is associated with gene expression and its possible involvement of lymphangiogenesis in gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Shunji Matsumura Abstract Previous studies have indicated that lymphangiogenesis in solid tumors is associated with lymphatic metastasis. Overexpression of Vascular endothelial growth factor (VEGF)-C plays a major role in lymphangiogenesis in cancers. In the present study, DNA methylation and expression of the VEGF-C gene was investigated in gastric cancer (GC). Four GC cell lines (MKN-45, MKN-74, HSC-39 and HSC-43) showed no expression of VEGF-C, and the VEGF-C gene was found to be methylated in these cells. In contrast, 7 GC cell lines (MKN-1, MKN-7, MKN-28, TMK-1, KATO-III, SH101-P4 and HSC-44PE) expressed VEGF-C, and the VEGF-C gene was found to be unmethylated in these cell lines. In addition, expression of VEGF-C mRNA was retrieved by treatment with a demethylating agent, Aza-2,-deoxycytidine. In GC tissue samples, bisulfite DNA sequencing analysis revealed that VEGF-C was not methylated in 9 (29.0%) of 31 GC samples, whereas demethylation was not observed in corresponding non-neoplastic mucosa samples. Overexpression of VEGF-C mRNA was observed in 16 (51.6%) of 31 GC samples by quantitative reverse transcription-polymerase chain reaction. Of the 9 GC cases with VEGF-C demethylation, 8 (88.9%) overexpressed VEGF-C. In contrast, of the 22 GC cases without VEGF-C demethylation, 8 (36.4%) overexpressed VEGF-C (p = 0.0155). Furthermore, lymphatic vessel density determined by immunostaining of podoplanin in GC tissues was associated with overexpression of VEGF-C (p < 0.0001). These results suggest that demethylation and activation of the VEGF-C gene is likely involved in lymphangiogenesis in GC. © 2007 Wiley-Liss, Inc. [source] Apocrine carcinoma of the vulva in a band-like arrangement with inflammatory and telangiectatic metastasis via local lymphatic channelsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2003Takahiro Kiyohara MD Background Primary adenocarcinomas of the vulva have been classified as sweat gland carcinomas, extramammary Paget's disease, and primary breast carcinomas of the vulva. They share some common histopathologic features. Methods We describe a 72-year-old Japanese woman with apocrine carcinoma of the vulva and local lymphatic metastasis. Results The patient presented with a bruise on her inguinal area. Physical examination revealed a 4 cm × 7 cm, dark-red, irregularly elevated tumor on the left labium majora. Dome-shaped, flesh-colored, small papulovesicles were scattered on the abdomen, accompanied by erythema and induration. The lesion showed a band-like arrangement. General examination revealed multiple bone metastases, particularly in the spine. Microscopic examination revealed a moderately differentiated adenocarcinoma with signet ring cells. A few pagetoid clear cells were present in the hypertrophic epidermis. The peripheral papulovesicles demonstrated the same histopathologic view as in inflammatory and telangiectatic, metastatic breast carcinoma. Tumor cells were positive for various ductal and glandular markers. Estrogen and progesterone receptors were not expressed. Ultrastructural findings suggested differentiation towards apocrine or mammary glands because of the presence of an apocrine process and electron-dense mucous granules. The patient died in spite of combination chemotherapy and irradiation therapy. Conclusions We report a rare case of apocrine carcinoma of the vulva in a band-like arrangement with local lymphatic metastasis which showed the clinical and histopathologic characteristics of inflammatory and telangiectatic carcinoma. [source] Expression of VEGF and its receptors Flt and KDR in gastric cancerJOURNAL OF DIGESTIVE DISEASES, Issue 4 2001Dongping Liu OBJECTIVE: The purpose of the present study was to investigate the correlation between the expression of vascular endothelial growth factor (VEGF), the expression of its receptors, Flt and KDR, and the biological behavior of gastric cancer. METHODS: Sixty cases of gastric cancer that had been diagnosed by surgery and pathology were studied with the method of semiquantitative reverse transcriptase,polymerase chain reaction (RT-PCR), to determine the expression of VEGF, Flt and KDR in gastric cancer tissue. RESULTS: The positive rates of VEGF, Flt and KDR in gastric cancer were 73.3, 86.7 and 80.0%, respectively. In pericancerous tissue, the rates were 43.3, 33.0 and 30.0%, respectively. There were significant differences between the groups with and without lymph node metastasis (P < 0.01). For gastric cancer patients with lymphatic metastasis, the positive rates for VEGF, Flt and KDR were 90.3, 80.6 and 96.8%, respectively; for patients without lymphatic metastasis, the rates were 51.7, 41.3 and 55.1%; there were significant differences between the groups with and without lymph node metastasis (P < 0.01). The positive rates of VEGF and KDR in well-differentiated gastric cancer were 40.0 and 46.7%, markedly lower than those of the poorly differentiated and undifferentiated gastric cancer groups. The rate of positive expression of Flt in the well-differentiated gastric cancer group was 73.3%. There was no significant difference between this rate and that of the poorly differentiated and undifferentiated groups (87.5%). The positive expression of VEGF, Flt and KDR was unrelated to the depth of infiltration. CONCLUSIONS: There are some correlations between VEGF, Flt and KDR and the biological behavior of gastric cancer. Knowing where they are expressed at high rates may be of help in evaluating the prognosis of gastric cancer. [source] Mechanisms of lymphatic metastasis in human colorectal adenocarcinoma,THE JOURNAL OF PATHOLOGY, Issue 5 2009Daniel Royston Abstract The invasion of lymphatic vessels by colorectal cancer (CRC) and its subsequent spread to draining lymph nodes is a key determinant of prognosis in this common and frequently fatal malignancy. Although tumoural lymphangiogenesis is assumed to contribute to this process, review of the current literature fails to support any notion of a simple correlation between lymphatic vessel density and CRC metastasis. Furthermore, attempts to correlate the expression of various lymphangiogenic growth factors, most notably VEGF-C and VEGF-D, with the lymphatic metastasis of CRC have provided contradictory results. Recent evidence from animal and human models of tumour metastasis suggests that complex functional and biochemical interactions between the microvasculature of tumours and other cell types within the tumour microenvironment may play a pivotal role in the behaviour of commonly metastasizing tumours. Indeed, previous insights into tumoural blood vessels have provided candidate markers of tumoural angiogenesis that are currently the subject of intense investigation as future therapeutic targets. In this review article we survey the current evidence relating lymphangiogenesis and lymphangiogenic growth factor production to metastasis by CRC, and attempt to provide some insight into the apparent discrepancies within the literature. In particular, we also discuss some new and provocative insights into the properties of tumoural lymphatics suggesting that they have specific expression profiles distinct from those of normal lymphatic vessels and that appear to promote metastasis. These findings raise the exciting prospect of future biomarkers of lymphatic metastasis and identify potential targets for new generation anti-tumour therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Distributions of Cervical Lymph Node Metastases in Oropharyngeal Carcinoma: Therapeutic Implications for the N0 NeckTHE LARYNGOSCOPE, Issue 7 2006Young Chang Lim MD Abstract Objectives: This study sought to investigate the patterns and distributions of lymph node metastases in oropharyngeal squamous cell carcinoma (SCC) and improve the rationale for elective treatment of N0 neck. Materials and Methods: One hundred four patients with oropharyngeal SCC who underwent neck dissection between 1992 and 2003 were analyzed retrospectively. All patients had curative surgery as their initial treatment for the primary tumor and neck. A total of 161 neck dissections on both sides of the neck were performed. Therapeutic dissections were done in 71 and 5 necks and elective neck dissection was done on 33 and 52 necks on the ipsilateral and contralateral sides, respectively. Surgical treatment was followed by postoperative radiotherapy for 78 patients. The follow-up period ranged from 1 to 96 months (mean, 30 months). Results: Of the 161 neck dissection specimens evaluated, 90 (56%) necks were found to have lymph node metastases found by pathologic examination. These consisted of 76 (73% of 104 necks) of the ipsilateral side and 14 (25% of 57 necks) of the contralateral side dissections. The occult metastatic rate was 24% (8 of 33) of ipsilateral neck samples and 21% (11 of 52) of contralateral neck samples. Of the 68 patients who had a therapeutic dissection on the ipsilateral side and had lymphatic metastasis, the incidence rate of level IV and level I metastasis was 37% (25 of 68) and 10% (7 of 68), respectively. Isolated metastasis to level IV occurred on the ipsilateral side in three patients. There were no cases of isolated ipsilateral level I pathologic involvement in an N-positive neck or occult metastasis to this group. The incidence rate of level IV metastasis in patients with ipsilateral nodal metastasis was significantly higher in base of tongue cancer (86% [6 of 7]) compared with tonsillar cancer (34% [20 of 59]) (P = .013). Patients with level IV metastasis had significantly worse 5-year disease-free survival rates than patients with metastasis to other neck levels (54% versus 71%; P = .04). Conclusion: These results suggest that elective N0 neck treatment in patients with oropharyngeal SCC, especially base of tongue cancer, should include neck levels II, III, and IV instead of levels I, II, and III. [source] PlGF expression in pre-invasive and invasive lesions of uterine cervix is associated with angiogenesis and lymphangiogenesisAPMIS, Issue 11 2009SHOUHUA YANG Most vascular endothelial growth factors (VEGF) have been shown to be associated with lymphangiogenesis and angiogenesis in various cancers. However, whether placental growth factor (PlGF), a rarely mentioned VEGF member, is involved in the pathogenesis of uterine cervical lesions remains unclear. To address this issue, we examined the relationship between PlGF expression and clinicopathologic variables in patients with pre-invasive and invasive lesions of uterine cervix. Sixty-two cervical specimens were immunostained with PlGF polyclonal antibody to define PlGF expression, and monoclonal antibodies D2-40 and CD34 to evaluate the lymphatic vessel density (LVD) and blood vessel density (BVD) of the lesions. PlGF mRNA level was detected by RT-PCR in all lesions from fresh tissues. We found that the levels of PlGF protein and mRNA expression were related to clinical stages (p < 0.05), but not to other clinicopathologic variables. No significant difference in PlGF expression was observed between squamous carcinoma and adenocarcinoma. Increased LVD and BVD were all associated with advanced stages (p < 0.001). Although LVD was strongly correlated with BVD, only high LVD was associated with pelvic lymphatic metastasis. Moreover, the level of PlGF expression was associated with both BVD(r = 0.715, p < 0.001) and LVD(r = 0.321, p < 0.05). Together, our study suggests that PlGF may participate in both tumor-associated angiogenesis and lymphangiogenesis of cervical carcinogenesis. [source] Expression and promoter methylation status of mismatch repair gene hMLH1 and hMSH2 in epithelial ovarian cancerAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 5 2008Hui ZHANG Objective: The purpose of this study is to determine the relationship between methylation and loss of hMLH1 and hMSH2 expression in ovarian cancer. Methods: We examined the methylation status of hMLH1 and hMSH2 promoter region by methylation-specific polymerase chain reaction (MSP) in 56 primary ovarian cancer tissues and 20 normal ovarian tissues, the relationship between the methylation status of these two genes and clinicopathological characteristics were analysed. We then treated SKOV3 and 3AO ovarian cancer cell lines with the demethylating agent 5-aza-2,-deoxycytidine (5-aza-dc). The hMLH1 and hMSH2 methylation was further assessed by MSP, and their mRNA expression was compared by reverse transcription polymerase chain reaction (RT-PCR) before and after 5-aza-dc treatment in these two cell lines. Results: The methylation frequency of hMLH1 and hMSH2 was 30.4% (17 of 56) and 51.7% (29 of 56) in ovarian cancers, respectively, while no methylation was detected in normal ovarian tissues (P = 0.015). There is a significant correlation between hMLH1 promoter hypermethylation and histological grade (P = 0.028) as well as lymphatic metastasis (P = 0.003). Methylation of hMSH2 correlated with histological grade (P = 0.035) and lymphatic metastasis (P = 0.015). Besides, the methylation rates of hMSH2 were significantly higher in endometrioid adenocarcinoma tissues than in other pathological types of ovarian cancer. After 5-aza-dc treatment, the expression of hMLH1 and hMSH2 was reversed in two cell lines. Conclusion: Our results indicate that promoter hypermethylation is an important mechanism for loss of hMLH1 and hMSH2 expression in human ovarian cancer and may be a potential prognostic factor in ovarian cancer. [source] |