Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

Itaru Kamata, Yukio Ishikawa, Yuri Akishima-Fukasawa, Kinji Ito, Yoshikiyo Akasaka, Miwa Uzuki, Ai Fujimoto, Hiroshi Morita, Seiichi Tamai, Tadaaki Maehara, Kentaro Ogata, Reiko Shimokawa, Yoshinori Igarashi, Kazumasa Miki, Toshiharu Ishii

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1527-1533
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume24
Issue number9
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Stomach Neoplasms
Lymph Nodes
Neoplasm Metastasis
Neoplasms
Matrix Metalloproteinase 1
Proteins
Catenins
Lymphatic Vessels
Claudin-3
Claudin-4
Immunohistochemistry
Claudins
CD44 Antigens
Matrix Metalloproteinase 2
von Willebrand Factor
Stromal Cells
Blood Vessels
Antibodies

Keywords

  • Gastric cancer
  • Lymph node metastasis
  • Lymphatic invasion
  • Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)
  • Matrix metalloproteinases (MMP)

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer. / Kamata, Itaru; Ishikawa, Yukio; Akishima-Fukasawa, 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.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 24, No. 9, 2009, p. 1527-1533.

Research output: Contribution to journalArticle

Kamata, I, Ishikawa, Y, Akishima-Fukasawa, Y, Ito, K, Akasaka, Y, Uzuki, M, Fujimoto, A, Morita, H, Tamai, S, Maehara, T, Ogata, K, Shimokawa, R, Igarashi, Y, Miki, K & Ishii, T 2009, 'Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer', Journal of Gastroenterology and Hepatology (Australia), vol. 24, no. 9, pp. 1527-1533. https://doi.org/10.1111/j.1440-1746.2009.05810.x
Kamata, Itaru ; Ishikawa, Yukio ; Akishima-Fukasawa, 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. / Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer. In: Journal of Gastroenterology and Hepatology (Australia). 2009 ; Vol. 24, No. 9. pp. 1527-1533.
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abstract = "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.",
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T1 - Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

AU - Kamata, Itaru

AU - Ishikawa, Yukio

AU - Akishima-Fukasawa, Yuri

AU - Ito, Kinji

AU - Akasaka, Yoshikiyo

AU - Uzuki, Miwa

AU - Fujimoto, Ai

AU - Morita, Hiroshi

AU - Tamai, Seiichi

AU - Maehara, Tadaaki

AU - Ogata, Kentaro

AU - Shimokawa, Reiko

AU - Igarashi, Yoshinori

AU - Miki, Kazumasa

AU - Ishii, Toshiharu

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Gastric cancer

KW - Lymph node metastasis

KW - Lymphatic invasion

KW - Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)

KW - Matrix metalloproteinases (MMP)

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