Detection of lymphatics and significance of lymphatic invasion on prognosis of gastrointestinal carcinoma using LYVE-1 antibody

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16590297
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Toho University
• Principal Investigator: ISHIKAWA Yukio Toho University, School of Medicine, Department of Pathology, Associated Professor, 医学部, 講師 (30276894)
• Co-Investigator(Kenkyū-buntansha): ISHII Toshiharu Toho University, School of Medicine, Department of Pathology, Professor, 医学部, 教授 (30101893) ; ITO Kinji Toho University, School of Medicine, Department of Pathology, Assistant Professor, 医学部, 助教授 (40057758) ; TERAMOTO Tatsuo Toho University, School of Medicine, Department of Surgery, Professor, 医学部, 教授 (00146713)
• Project Period (FY): 2004 – 2005
• Keywords: LYVE-1 / lynphatics / normal gastrointestinal tracts / lymphatic invasion / early gastric cancer / colonic cancer / immunohistochemistry / prognostic factor

Research Abstract

1.Preparation of affinity purified anti-LYVE-1 antibody
Using New Zealand White rabbits, antisera were raised against the 13-mer peptide corresponding to amino acids 297-308 of the LYVE-1 sequence. The specificity of the antibody was ascertained, and the antibody was used for immunohistochemistry on the normal and pathological gastrointestinal tissues.
2.Distribution of lymphatic vessels in the normal structures of the gastrointestinal tissues.
In the normal esophagus, stomach and colon, LYVE-1 positive lymphatics were abundant in the submucosal layer and were distributed along with the running course of blood vessels in the proprial muscle layer. In the gastric mucosa, lymphatic capillaries were sporadically seen, but the mucosal layers of the esophagus and colon had no lymphatic structure. LYVE-1 immunohistochemistry could discriminate lymphatics from blood vessels.
3.Lymphatic distribution and lymphatic invasion in the early gastric cancer
LYVE-1 positive lymphatics were recognized in th e interstitium around the tumor but never in the tumor interstitium. Lymphatics invaded by cancer cells were rarely observed, and the number of lymphatic invasion was significantly larger in the group with LN metastasis than in the group without LN metastasis. In addition, when the number of lymphatics invaded by cancer cells was 2> in one field (X200), LN metastasis was found in 80% cases. Our results indicate that LYVE-1 immunohistochemistry is useful for a prediction of LN metastasis in the early gastric cancer.
4.Lymphangiogenesis and lymphatic invasion in the colonic cancer
The number of lymphatics around the colonic adenocarcinoma did not increase comparing to the normal corresponding structures, and there was no significant association of the number of lymphatics around the tumor with LN status. However, VEGF-C, a factor of lymphatic endothelial growth factor, was expressed in 82 cases (51%). This fact suggested that pre-existing lymphatics were destroyed by cancer cell invasion, and cancer invasion may surpass newly formed lymphatics. The number of lymphatics invaded by cancer cells was significantly larger in the group with LN metastasis than in the group without LN metastasis.
From our results, it is considered that immunohistochemistry using LYVE-1 antibody is quietly useful for examination of lymphatic invasion by cancer cells as well as the prediction of LN metastasis in gastrointesitinal malignancies.

Research Products

• [Journal Article] Significance of lymphatic invasion on regional lymph node (2006)
  • Author(s): Fujimoto A, Ishikawa Y, et al.
  • Journal Title: Virchows Arch In press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The human renal lymphatics under normal and pathological (2006)
  • Author(s): Ishikawa Y, Akasaka Y, et al.
  • Journal Title: Histopathology In press
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Significance of lymphatic invasion on regional lympha node metastasis in early gastric cancer using LYVE-1 immunohistochemistry (2006)
  • Author(s): Fijimoto A, Ishikawa Y, Akishima-Fukasawa Y, Ito K, Akasaka Y, Tamai S, Maehara T, Kiguchi H, Ogata K, Nishimura C, Miki K, Ishui T
  • Journal Title: Virchows Arch (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The human renal lymphatics under normal and pathological conditions. (2006)
  • Author(s): Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S, Ishii T
  • Journal Title: Histopathology (in press)
  • Description: 「研究成果報告書概要(欧文)」より