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Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma
Author(s) -
Kondo Yoko,
Arii Shigeki,
Furutani Masaharu,
Isigami ShunIchi,
Mori Akira,
Onodera Hisashi,
Chiba Tsutomu,
Imamura Masayuki
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000415)88:8<1820::aid-cncr10>3.0.co;2-5
Subject(s) - angiogenesis , medicine , vascular endothelial growth factor , pathology , immunohistochemistry , submucosa , carcinoma , microvessel , colorectal cancer , atypia , neovascularization , cancer , cancer research , vegf receptors
BACKGROUND It still is unclear when angiogenic potential, which is believed to be a prerequisite for tumor development, is acquired. The current study was designed 1) to clarify when the phenotypic change of angiogenicity occurs during the development of colon carcinoma and 2) to investigate the possible roles of vascular endothelial growth factor (VEGF) and p53 in angiogenesis. METHODS Colon carcinomas were classified according to the following criteria: m carcinomas were tumors in which carcinoma cells were observed within the mucosa (excluding adenomas with severe atypia) according to the World Health Organization criteria. sm carcinomas were defined by invasion into the submucosa but not into the muscularis propria. Using 27 adenomas, 26 m carcinomas, and 20 sm carcinomas, VEGF expression was analyzed with reverse transcriptase‐polymerase chain reaction and immunohistochemistry. Microvessel density, VEGF, and p53 status were evaluated by immunohistochemistry. RESULTS Neither VEGF mRNA nor VEGF protein was detected in any of the mild‐to‐moderate dysplastic adenomas, whereas 16 of 26 m carcinomas (62%) and all sm carcinomas exhibited VEGF protein. The microvessel density in adenomas, m carcinomas, and sm carcinomas was 3 ± 0.55, 6.1 ± 1.12, and 12 ± 1.35 (0.739 mm 2 per field), respectively. In m carcinomas, positive VEGF expression was coincident with the expression of p53, and stainability for both VEGF and p53 was similar with regard to spatial distribution in tumor tissues. In m and sm carcinomas, there was a statistically significant correlation between the intensity of VEGF expression and microvessel density. CONCLUSIONS The results of the current study demonstrated that angiogenesis develops in association with tumor progression from adenoma to noninvasive colorectal carcinoma, at least in part due to VEGF, and suggested that VEGF in m carcinomas is induced by mutant p53, although alternative mechanisms of VEGF up‐regulation may exist in sm carcinomas. Cancer 2000;88:1820–7. © 2000 American Cancer Society.