Peritumoral lymphatic invasion is associated with regional lymph node metastases in prostate adenocarcinoma

Abstract

Lymphangiogenesis, detected by antibodies specific for lymphatic endothelial cells, has been associated with regional lymph node metastases and poor prognosis in carcinomas of head and neck, breast and uterine cervix, but remains largely uninvestigated in prostate adenocarcinoma. We evaluated the lymphatic vessel density and lymphatic vessel invasion by prostate cancer cells in the intratumoral, peritumoral and normal prostate tissue compartments in cancer-bearing prostate glands and correlated them with lymph node metastases, Gleason score and other pathological parameters. Lymphatic vessels were detected by immunohistochemical stain using an antibody specific for the lymphatic endothelial cells (clone D2-40) on 33 radical prostatectomies. In all, 26 patients had lymph node dissection, and 14 of them had lymph node metastasis. The lymphatic vessel density and lymphatic vessel invasion were then recorded for each of the three compartments microscopically. Lymphatic vessel density in the intratumoral, peritumoral and normal prostate compartments was 0.9170.80, 1.5470.68 and 1.5870.96/mm 2 , respectively. The intratumoral lymphatic vessel density was significantly lower than that of the peritumoral and normal prostate compartments, and the latter two were not significantly different. The lymphatic vessel density of the three compartments was not significantly different between cases with and without lymph node metastasis. The peritumoral lymphatic vessel density correlated inversely with the Gleason score. Lymphatic vessel invasion was present in significantly higher percentage of cases with lymph node metastasis (9/14, 62.3%), as compared to those without lymph node metastasis (1/12, 8.3%, Po0.01). The peritumoral lymphatic vessel invasion had a better correlation with the presence of lymph node metastases than intratumoral lymphatic vessel invasion. There is no evidence of lymphangiogenesis in prostate adenocarcinoma. Peritumoral lymphatic vessel invasion correlates with regional lymph node metastases, suggesting that the peritumoral lymphatic vessels are functionally important and identification of lymphatic vessel invasion in this compartment implies a high probability of regional lymph node metastases. Modern Pathology (2006) 19, 392-398. doi:10.1038/modpathol.3800546; published online 6 January 2006 Keywords: prostate adenocarcinoma; lymphatic vessels; lymphangiogenesis; lymph node metastases Metastasis is the hallmark of malignant neoplasms and the lymphatic system provides a key route for neoplastic dissemination.1,2 Recent experimental evidence suggests that a wide variety of tumor cells can produce several lymphangiogenic factors, including vascular endothelial growth factor C and D (VEGF C and D), that promote the growth and remodeling of lymphatic vessels, a process termed lymphangiogenesis, through interaction with a cell surface receptor tyrosine kinase, vascular endothelial growth factor receptor 3 (VEGFR-3).2-6 Studies have also demonstrated that the expression of these lymphangiogenic factors corr...

Periacinar Retraction Clefting and D2-40 Expression in Prostatic Adenocarcinoma

“…Some studies suggest that lymph vessel density inside intratumoral compartment of prostatic carcinoma is reduced [22,23] as it is in our study. Roma et al [22] associated higher peritumoral lymphatic vessel density with higher Gleason score and peritumoral invasion with frequent lymph node metastasis.…”

“…Some studies suggest that lymph vessel density inside intratumoral compartment of prostatic carcinoma is reduced [22,23] as it is in our study. Roma et al [22] associated higher peritumoral lymphatic vessel density with higher Gleason score and peritumoral invasion with frequent lymph node metastasis. Cheng et al [23] did not correlate these findings and concluded that quantification of lymphangiogenesis in prostate adenocarcinoma does not offer useful prognostic information.…”

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

“…Several studies have shown that peritumoral lymphatic vessels are associated with lymph node metastasis, 8,14,17,18,27,40,41 whereas other studies, only for head and neck squamous cell carcinoma, showed that intratumoral lymphatic vessels, and not peritumoral lymphatic vessel density, are important for lymphatic spreads. 3,14,15 Thus, we first examined the VEGF-C and D2-40 expression in cholangiocarcinoma S Aishima et al intratumoral or peritumoral lymphatic vessel density in intrahepatic cholangiocarcinomas, and detected the following: (1) lymphatic vessel density was much lower in the tumor center than in the tumor periphery; (2) lymphatic vessels in the tumor center were frequently collapsed, whereas peritumoral lymphatic vessels showed open lumen; and (3) lower lymphatic vessel density in the tumor center was significantly correlated with the presence of lymphatic invasion.…”

“…11,44 It was demonstrated that increased lymphangiogenic activity is not required for the lymphatic spread in pancreatic ductal adenocarcinoma, 7,9 and prostatic adenocarcinoma. 8,22 Several studies showed that increased lymphatic perimeters and areas were found to be correlated with presence of lymphatic metastasis. 17,39,40,42 Therefore, lymphatic invasion in intrahepatic cholangiocarcinoma is independent of the active lymphangiogenesis, but other possible factors are expected for the lymphatic spread.…”

“…1,2 Several types of human cancer can induce the formation of lymphatic vessels, [3][4][5][6] whereas other cancers do not actively induce lymphangiogenesis and simply invade existing lymphatic vessels. [7][8][9][10][11][12][13] A positive relationship between the intratumoral or peritumoral lymphatic vessel density and lymphatic spreads has been reported in head and neck squamous cell carcinoma, 3,14,15 cutaneous melanoma, 16,17 lung cancer, 18 and pancreatic endocrine tumor. 19,20 Vascular endothelial growth factor-C (VEGF-C) has been found to be the common lymphangiogenetic factor, acting predominantly via VEGF receptor-3 (VEGFR-3), which is expressed by lymphatic endothelial cells, 21 and VEGF-C strongly promoted the growth of tumor-associated lymphatic vessels.…”