Expression of Tumor-Associated Membrane Antigen, RCAS1, in Human Colorectal Carcinomas and Possible Role in Apoptosis of Tumor-Infiltrating Lymphocytes

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.

[1]  賢 久保川.  Aberrant intracellular localization of RCAS1 is associated with tumor progression of gastric cancer , 2005 .

[2]  T. Oshikiri,et al.  High expression of tumor‐associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker , 2002, International journal of cancer.

[3]  T. Koji,et al.  Fas-Mediated Apoptosis of Melanoma Cells and Infiltrating Lymphocytes in Human Malignant Melanomas , 2002, Modern Pathology.

[4]  T. Oshikiri,et al.  The prognostic significance of RCAS1 expression in squamous cell carcinoma of the oesophagus. , 2002, Cancer letters.

[5]  T. Oshikiri,et al.  RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer , 2001, British Journal of Cancer.

[6]  S. Inoue,et al.  EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine–immune interactions , 2001, British Journal of Cancer.

[7]  K. Sugimachi,et al.  Expression of a tumor-associated antigen RCAS1 in hepatocellular carcinoma. , 2001, Cancer letters.

[8]  Y. Nakanishi,et al.  Expression of tumor‐associated antigen RCAS1 correlates significantly with poor prognosis in nonsmall cell lung carcinoma , 2001, Cancer.

[9]  K. Ohshima,et al.  Expression of human tumor‐associated antigen RCAS1 in Reed‐Sternberg cells in association with Epstein‐Barr virus infection: A potential mechanism of immune evasion , 2001, International journal of cancer.

[10]  K. Ohshima,et al.  Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy: the possible role in immune privilege , 2001, Clinical and experimental immunology.

[11]  T. Kanematsu,et al.  Frequency of apoptosis of tumor-infiltrating lymphocytes induced by fas counterattack in human colorectal carcinoma and its correlation with prognosis. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  M. Nakashima,et al.  Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1 , 1999, Nature Medicine.

[13]  T. Kaku,et al.  The prognostic significance of tumor-associated antigen 22-1-1 expression in adenocarcinoma of the uterine cervix. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[14]  F. Shanahan,et al.  The Fas counterattack: cancer as a site of immune privilege. , 1999, Immunology today.

[15]  N. Restifo,et al.  T cell–tumor cell: a fatal interaction? , 1998, Cancer Immunology, Immunotherapy.

[16]  H Nagura,et al.  CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. , 1998, Cancer research.

[17]  T. Kaku,et al.  Tumor-associated antigen 22-1-1 expression in the uterine cervical squamous neoplasias. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  C. Brady,et al.  The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. , 1998, Journal of immunology.

[19]  P. Galle,et al.  Immune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its clinical implications. , 1998, Molecular medicine today.

[20]  T. Koji,et al.  Frequency of apoptosis relates inversely to invasiveness and metastatic activity in human colorectal cancer , 1997, Virchows Archiv.

[21]  V. Kosma,et al.  Prognostic value of tumour‐infiltrating lymphocytes (TILs) in colorectal cancer , 1997, The Journal of pathology.

[22]  P. Walker,et al.  Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back. , 1997, Journal of immunology.

[23]  J. Gribben,et al.  Breast cancer–associated antigen, DF3/MUC1, induces apoptosis of activated human T cells , 1996, Nature Medicine.

[24]  S. Nagata.  Fas ligand and immune evasion , 1996, Nature Medicine.

[25]  J. Tschopp,et al.  Melanoma Cell Expression of Fas(Apo-1/CD95) Ligand: Implications for Tumor Immune Escape , 1996, Science.

[26]  F. Shanahan,et al.  The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand , 1996, The Journal of experimental medicine.

[27]  T. Koji.  Nonradioactive in Situ Nick Translation : A Useful Molecular Histochemical Tool to Detect Single-Stranded DNA Breaks , 1996 .

[28]  園田 顕三.  A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas , 1996 .

[29]  C A Smith,et al.  Identification and characterization of a new member of the TNF family that induces apoptosis. , 1995, Immunity.

[30]  T. Koji,et al.  Differential staining of DNA strand breaks in dying cells by non-radioactive in situ nick translation. , 1995, Archives of histology and cytology.

[31]  S. Nagata,et al.  Purification and characterization of the Fas-ligand that induces apoptosis , 1994, The Journal of experimental medicine.

[32]  Takashi Suda,et al.  Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor family , 1993, Cell.

[33]  Heppner Gh,et al.  Cell-to-cell interaction in regulating diversity of neoplasms. , 1991 .