Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer
Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer
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DOI：
10.1111/j.1440-1746.2009.05810.x
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发表时间：
2009-09-01
影响因子：
4.1
通讯作者：
Ishii, Toshiharu
中科院分区：
文献类型：
--
作者：
Kamata, Itaru;Ishikawa, Yukio;Ishii, Toshiharu
背景与目的：胃癌的侵袭和转移是影响患者预后的重要因素，但胃癌淋巴结转移过程中最重要的环节仍不清楚。本研究采用免疫组化方法，探讨胃癌局部淋巴结转移与癌细胞行为（如细胞脱落、间质浸润和淋巴管浸润）的关系。其中有局部淋巴结转移者105例（LN+组），无淋巴结转移者105例（LN-组）。两组均表现出相同的浸润深度。癌组织进行免疫组织化学与抗体的claudin-3，claudin-4，β-连环蛋白，基质金属蛋白酶（MMP）-1，MMP-2，以及内皮标志物的淋巴管内皮透明质酸受体-1和von Willebrand因子之间的客观区分血管和血管。结果：沿着癌细胞的淋巴管浸润和肿瘤的大小，MMP-1在原发灶浸润前沿的表达是LN转移的一个重要的独立预测因子。claudins和beta-catenin的表达与胃癌的组织病理学类型有关，而与LN状态无关。结论：在检测的肿瘤侵袭相关蛋白中，MMP-1在胃癌LN转移中起重要作用。肿瘤大小、淋巴结转移和浸润前沿MMP-1表达水平是胃癌淋巴结转移的预测因素。
Background and Aims:Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry.Methods:A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[-] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, beta-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(-) groups.Results:Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and beta-catenin was associated with the histopathological type of cancer, but not with LN status.Conclusion:Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.