Cellular and Molecular Biology


Loss of MUC2 expression correlates with progression along the adenoma-carcinoma sequence pathway as well as de novo carcinogenesis in the colon

T. Mizoshita1, T. Tsukamoto1, K-I. Inada1,2, N. Hirano1, M. Tajika3, T. Nakamura3, H. Ban1 and M. Tatematsu1

1Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan,
2Department of Pathology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan, and 3Department of Gastroenterology, Aichi Cancer Center Hospital, Chikusa, Nagoya, Japan

Offprint requests to: Tetsuya Tsukamoto, MD, Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. e-mail: ttsukamt@aichi-cc.jp

Summary. Aims: We have previously demonstrated links between clinicopathological findings and phenotypes using several gastric and intestinal phenotypic markers in stomach and pancreatic cancers. However, the clinicopathological significance of the phenotype and Cdx2 expression has hitherto remained unclear in colorectal carcinogenesis. Methods and results: We examined the correlation between gastric and intestinal phenotypic expression in 91 primary early carcinomas of the colon. MUC2 expression demonstrated a significant decrease from tubular/tubulovillous adenomas with moderate atypia, through intramucosal carcinomas, to cancers with submucosal invasion (P<0.0001). Intramucosal de novo carcinomas (flat type carcinomas without adenomatous components) exhibited a greater decrease of MUC2 than intramucosal lesions with adenomatous components. Expression of MUC5AC also decreased significantly with progression according to the tubular/tubulovillous adenoma-carcinoma sequence, carcinomas with villous adenomatous components having a higher level compared with their tubular adenomatous counterparts, suggesting differences in the pathway of malignant transformation. Cdx2 nuclear expression was maintained in all of the adenomas and early carcinomas examined. Conclusions: Our data suggest that the reduction of MUC2 expression may be associated with the occurrence and progression of colorectal carcinomas in both adenoma-carcinoma sequence pathway and de novo carcinogenesis. Tumor-suppressive effects of Cdx2 may be preserved during early stages of colorectal carcinogenesis. Histol Histopathol 22, 251-260 (2007)

Key words: Colorectal carcinomas, Colorectal adenomas, MUC2, Cdx2, MUC5AC

DOI: 10.14670/HH-22.251