Špirić Zorica, Eri Živka, Erić Mirela
Clinical Center of Banja Luka, Republic of Srpska, Bosnia and Herzegovina
Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Int J Surg Pathol. 2015 Dec;23(8):629-37. doi: 10.1177/1066896915583694. Epub 2015 Apr 24.
Induction of tumor lymphangiogenesis by vascular endothelial growth factor (VEGF)-C and VEGF-D promotes metastasis in many human cancers.
The aim of this study was to examine the role of VEGF-C and VEGF-D in lymphangiogenesis and lymph node metastasis in patients with cutaneous melanoma.
Fifty-four melanoma specimens (18 with lymph node metastasis, 36 nonmetastatic) were investigated by immunostaining for VEGF-C, VEGF-D, and for lymphatic endothelial marker D2-40. VEGF-C and VEGF-D expression was assessed as a percentage and intensity of stained tumor cells, tumor-associated macrophages and fibroblasts. The quantification of lymphangiogenesis was conducted by computer-assisted morphometric analysis.
The expressions of both VEGF-C and VEGF-D in tumor cells were significantly higher in lymph node metastatic melanomas compared with nonmetastatic melanomas (P = .015 VEGF-C; P = .005 VEGF-D). There was no statistically significant difference between metastatic and nonmetastatic melanomas regarding the expression of VEGF-C and VEGF-D in macrophages and fibroblasts. Metastatic melanomas showed a significantly higher intratumoral and peritumoral lymphatic vessel density (LVD) compared with nonmetastatic melanomas (P = .000 intratumoral, P = .000 peritumoral). Melanomas with VEGF-C positive tumor cells showed a significantly higher intratumoral and peritumoral LVD compared with VEGF-C negative tumor cells group of melanomas (P = .006 intratumoral, P = .010 peritumoral). VEGF-C expression in macrophages, fibroblasts, as well as VEGF-D expression in tumor cells, macrophages, and fibroblasts, showed no correlation with the intratumoral and peritumoral LVD.
Our findings show the significance of VEGF-C in tumor cells in the induction of intratumoral and peritumoral lymphangiogenesis. This study suggests that both VEGF-C and VEGF-D in tumor cells promote lymph node metastasis, and that the immunohistochemical analysis of expression can be a useful tool for predicting clinical behavior of cutaneous melanoma.
血管内皮生长因子（VEGF）-C和VEGF-D诱导肿瘤淋巴管生成促进多种人类癌症的转移。
本研究旨在探讨VEGF-C和VEGF-D在皮肤黑色素瘤患者淋巴管生成和淋巴结转移中的作用。
对54例黑色素瘤标本（18例有淋巴结转移，36例无转移）进行免疫染色，检测VEGF-C、VEGF-D及淋巴管内皮标志物D2-40。以染色肿瘤细胞、肿瘤相关巨噬细胞和成纤维细胞的百分比和强度评估VEGF-C和VEGF-D的表达。通过计算机辅助形态计量分析对淋巴管生成进行定量。
与无转移黑色素瘤相比，有淋巴结转移的黑色素瘤肿瘤细胞中VEGF-C和VEGF-D的表达均显著更高（VEGF-C，P = 0.015；VEGF-D，P = 0.005）。在巨噬细胞和成纤维细胞中，转移和未转移黑色素瘤的VEGF-C和VEGF-D表达无统计学显著差异。与无转移黑色素瘤相比，转移黑色素瘤的瘤内和瘤周淋巴管密度（LVD）显著更高（瘤内，P = 0.000；瘤周，P = 0.000）。VEGF-C阳性肿瘤细胞的黑色素瘤与VEGF-C阴性肿瘤细胞组的黑色素瘤相比，瘤内和瘤周LVD显著更高（瘤内，P = 0.006；瘤周，P = 0.010）。巨噬细胞和成纤维细胞中的VEGF-C表达以及肿瘤细胞、巨噬细胞和成纤维细胞中的VEGF-D表达与瘤内和瘤周LVD均无相关性。
我们的研究结果表明肿瘤细胞中的VEGF-C在诱导瘤内和瘤周淋巴管生成中具有重要意义。本研究提示肿瘤细胞中的VEGF-C和VEGF-D均促进淋巴结转移，且表达的免疫组化分析可作为预测皮肤黑色素瘤临床行为的有用工具。
