Ishikawa Makoto, Kitayama Joji, Kazama Shinsuke, Nagawa Hirokazu
Department of Surgery, Division of Surgical Oncology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
World J Surg Oncol. 2005 Jan 7;3(1):2. doi: 10.1186/1477-7819-3-2.
Vascular endothelial growth factor (VEGF)-C is implicated in lymphangiogenesis, however the exact role of VEGF-C in promoting lymphatic spread of cancer cells remains largely unknown. METHODS: The expression of VEGF-C was immunohistochemically determined in 97 endoscopic biopsy specimens from 46 patients with submucosal gastric carcinoma (SGC). Nodal metastases including micrometastasis and isolated tumor cells (ITC) were evaluated by immunohistochemical staining for cytokeratin in 1650 lymph nodes, and tumor cells in these metastatic nodes were also examined for VEGF-C expression. RESULTS: In biopsy samples, VEGF-C was positively detected in 21 (47%) patients. Metastases were identified in 46 (2.8%) nodes from 15 (33%) patients. Metastases were detected in 39 nodes by hematoxylin-eosin (H&E) staining and in additional 7 nodes as ITC by immunohistochemical staining. The rate of lymph node metastases was significantly correlated with VEGF-C expression in biopsy samples (p < 0.05). The positive and negative predictive values of VEGF-C in biopsy specimens for nodal metastasis were 44 %(10/21) and 80% (20/25), respectively. Among the 46 metastatic nodes, tumor cells in 29 (63%) nodes positive patients expressed VEGF-C, whereas those in 17 (37%) nodes did not. VEGF-C expression was high in macronodular foci in medullary areas, whereas more than half of ITC or micrometastasis located in peripheral sinus lacked the expression of VEGF-C. CONCLUSIONS: Despite the significant correlation, immunodetcetion of VEGF-C in endoscopic biopsy specimens could not accurately predict the nodal status, and thus cannot be applied for the decision of the treatment for SGC. VEGF-C may not be essential for lymphatic transport, but rather important to develop the macronodular lesion in metastatic nodes.
血管内皮生长因子（VEGF）-C与淋巴管生成有关，然而VEGF-C在促进癌细胞淋巴转移中的确切作用仍不清楚。方法：对46例黏膜下胃癌（SGC）患者的97份内镜活检标本进行免疫组织化学检测VEGF-C的表达。通过对1650个淋巴结进行细胞角蛋白免疫组织化学染色评估包括微转移和孤立肿瘤细胞（ITC）在内的淋巴结转移情况，并且对这些转移淋巴结中的肿瘤细胞也检测VEGF-C表达。结果：在活检样本中，21例（47%）患者VEGF-C呈阳性检测。在15例（33%）患者的46个（2.8%）淋巴结中发现转移。苏木精-伊红（H&E）染色在39个淋巴结中检测到转移，免疫组织化学染色在另外7个淋巴结中检测到ITC转移。活检样本中淋巴结转移率与VEGF-C表达显著相关（p<0.05）。活检标本中VEGF-C对淋巴结转移的阳性和阴性预测值分别为44%（10/21）和80%（20/25）。在46个转移淋巴结中，29例（63%）淋巴结阳性患者的肿瘤细胞表达VEGF-C，而17例（37%）淋巴结中的肿瘤细胞不表达。VEGF-C在髓质区的大结节灶中表达较高，而位于外周窦的ITC或微转移中超过一半缺乏VEGF-C表达。结论：尽管存在显著相关性，但内镜活检标本中VEGF-C的免疫检测不能准确预测淋巴结状态，因此不能用于SGC治疗方案的决策。VEGF-C可能对淋巴转运不是必需的，但对转移淋巴结中大结节病变的形成很重要。
