Original Article
Mod Pathol 2003;16(7):679–685
Expression of Tumor-Associated Membrane Antigen, RCAS1, in Human Colorectal Carcinomas and Possible Role in Apoptosis of Tumor-Infiltrating Lymphocytes
Kazuya Okada M.D.1, Manabu Nakashima M.D.3, Ko Komuta M.D.1, Satoshi Hashimoto M.D.1, Sadayuki Okudaira M.D.1, Nobuyuki Baba M.D.2, Yoshitaka Hishikawa M.D.2, Takehiko Koji Ph.D.1, Takashi Kanematsu M.D.2 and Takeshi Watanabe M.D.3
- 1Department of Surgery II, Nagasaki University School of Medicine, Nagasaki, Japan
- 2Department of Histology and Cell Biology, Nagasaki University School of Medicine, Nagasaki, Japan
- 3Department of Molecular Immunology, Medical Institute of Bioregulation, Kyusyu University, Fukuoka, Japan
Correspondence: Takeshi Watanabe, M.D., Department of Molecular Immunology, Medical Institute of Bioregulation, Kyusyu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. fax: 81-92-632-1499; e-mail: watanabe@bioreg.kyushu-u.ac.jp.
Accepted 6 March 2003.
Abstract
RCAS1, a novel tumor-associated antigen, is expressed in advanced human neoplasias including uterine and ovarian carcinomas. RCAS1 protein was indicated to induce cell cycle arrest and apoptosis of cultured human lymphoid and myeloid cell lines and normal lymphocytes. In the present study, we investigated the expression and prognostic value of RCAS1 in 58 patients with colorectal carcinomas. RCAS1 protein was detected by immunoperoxidase staining using a mouse monoclonal anti-RCAS1 antibody (22-1-1 antibody). Immunohistochemical examination showed expression of RCAS1 in 75% of colorectal carcinomas with lymph node metastases (n = 24), whereas it was present in only 41% of tumors without metastases (n = 34, P < .05). Patients with RCAS1-positive tumors showed a significantly poorer prognosis than those negative for RCAS1 (P < .05). Multivariate analysis using the Cox regression model indicated that RCAS1 positivity was an independent negative predictor for survival (P = .0300; risk ratio, 0.496). In addition, apoptotic cells of tumor-infiltrating lymphocytes were examined using nonradioactive in situ nick translation in paraffin-embedded sections. The proportion of apoptotic tumor-infiltrating lymphocytes was significantly higher in RCAS1-positive colorectal carcinomas (11.2 
1.0) than in RCAS1-negative tumors (7.9 1.0, P < .05). Our results suggest that overexpression of RCAS1 may negatively affect the prognosis of human colorectal carcinomas and that RCAS1 may play a role in tumor immune privilege in vivo.
Keywords:
Apoptosis, Colorectal cancer, Fas, Fas ligand, RCAS1, Tumor-infiltrating lymphocytes
