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Significance of lymphatic invasion and cancer invasion‐related proteins on lymph node metastasis in gastric cancer
Author(s) -
Kamata Itaru,
Ishikawa Yukio,
AkishimaFukasawa Yuri,
Ito Kinji,
Akasaka Yoshikiyo,
Uzuki Miwa,
Fujimoto Ai,
Morita Hiroshi,
Tamai Seiichi,
Maehara Tadaaki,
Ogata Kentaro,
Shimokawa Reiko,
Igarashi Yoshinori,
Miki Kazumasa,
Ishii Toshiharu
Publication year - 2009
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2009.05810.x
Subject(s) - lymphovascular invasion , metastasis , cancer , medicine , pathology , lymphatic system , lymphatic vessel , cancer cell , immunohistochemistry , stromal cell , lymphangiogenesis
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, β‐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 β‐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.