RCAS1 as a tumour progression marker: an independent negative prognostic factor in gallbladder cancer

Abstract

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) induces apoptosis in immune cells bearing the RCAS1 receptor. We sought to determine RCAS1 involvement in the origin and progression of gallbladder cancer, and also implications of RCAS1 for patient survival. RCAS1 expression was examined immunohistochemically in 110 surgically resected gallbladder specimens. The gallbladders represented 20 cases of cholecystitis with no associated pancreaticobiliary maljunction; 23 cases of cholecystitis with pancreaticobiliary maljunction; 14 cases of adenomyomatosis; 7 adenomas; and 46 cancers. High expression of RCAS1 (immunoreactivity in over 25% of cells) was observed in 32 of the 46 cancers (70%), but not in other diseases, including pre-cancerous conditions. RCAS1 immunoreactivity was associated with depth of tumour invasion ( P = 0.0180), lymph node metastasis ( P = 0.0033), lymphatic involvement ( P = 0.0104), venous involvement ( P = 0.0224), perineural involvement ( P = 0.0351) and stage by the tumour, nodes and metastases (TNM) classification ( P = 0.0026). Thus, RCAS1 expression may be a relatively late event in gallbladder carcinogenesis possibly promoting tumour progression. Cox regression multivariate analysis demonstrated RCAS1 positivity to be an independent negative predictor for survival ( P = 0.0337; risk ratio, 12.690; 95% confidence interval, 1.216–132.423). High expression of RCAS1 significantly correlated with tumour progression and predicted poor outcome in gallbladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

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

“…Expression of RCAS1 correlates with invasion or progression in several carcinomas (2,9,10). In addition, RCAS1 expression is associated with poor prognosis in uterine, lung, gallbladder, pancreas, and esophageal carcinoma (11)(12)(13)(14)(15). Although previous studies suggested that RCAS1 is also expressed in colorectal carcinoma cells, the relationship between RCAS1 expression and prognosis in colorectal carcinomas is not known at present.…”

Receptor-binding cancer antigen expressed on SiSo cells can be detected in metastatic lymph nodes from gastrointestinal cancers

“…As suspected, it was expressed in all cases of metastatic lymph nodes. RCAS1 was shown to be a ligand for a putative receptor on immune cells such as T cells and natural killer cells [7][8][9][10][11][12][13][14] . Scientists suggest that RCAS1 may play a protective role in tumor cells against immune surveillance by inhibition of clonal expression and inducing receptor-expressing cell death.…”

“…This tumor-associated antigen has been demonstrated in several kinds of gastrointestinal cancer by immunohistochemical study using the specific mouse mAb, 22-1-1. The result of RCAS1 expression was evaluated for the percent incidence in various cancers including gall bladder cancer (70%) [9] , cholangiocarcinoma (85.9-96.4%) [10,11] , gastric cancer (54.3%) [12] , pancreatic cancer (100%) [13] , and colorectal cancer (100%) [14] . However, until now, there has been no intensive study about the expression of RCAS1 in lymph node metastasis from gastrointestinal cancer.…”

Analysis of cell cycle arrest and apoptosis induced by RCAS1

“…It also exists in soluble form, probably through alternative splicing (2). Immunohistochemical studies show that RCAS1 is expressed in various malignant tumors, and its expression is one of the important clinicopathological parameters correlating with patient survival (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Soluble RCAS1 has also been detected in blood serum by enzyme-linked immunosorbent assay (ELISA), and is probably released from the membrane as a result of ectodomain shedding (14,15).…”