Reduced E-Cadherin Expression as a Cause of Distinctive Signet-Ring Cell Variant in Colorectal Carcinoma

Colorectal signet-ring cell carcinoma (SRCC) is a rare type of adenocarcinoma and presents with distinctive clinicopathological features. This study was performed to assess the biological characteristics of colorectal SRCC regarding the E-cadherin expression. Seventeen patients with primary colorectal SRCC were identified and their clinicopathological characteristics were analyzed. The mean age of the 17 patients was 45.3 yr (14-68). Immunohistochemical staining of E-cadherin and beta-catenin were performed in ten colorectal SRCCs and in 30 ordinary colorectal adenocarcinomas as control. Primary colorectal SRCC occurred in 0.7% of 2,388 colorectal adenocarcinomas. Most patients had advanced stage tumor at surgery (stage III and IV, AJCC: 82%). Five-year survival rate was 16%. Peritoneal seeding was the most common recurrence pattern (41%) and liver metastasis was not identified. All SRCCs showed a markedly reduced or absent expression of E-cadherin on immunohistochemical staining, whereas seven (23.3%) of ordinary carcinomas showed reduced expression, thereby indicating a significant difference between the two groups (p<0.005). In immunohistochemical staining for beta-catenin, eight of ten SRCCs showed reduced membrane expression that did not attain statistical significance compared to ordinary adenocarcinomas. It is suggested that aberrant E-cadherin expression may explain the distinct clinicopathological features in primary colorectal SRCC.

Prognostic significance of E-cadherin/catenin complex expression in gastric cancer

Abnormal expression of E-cadherin/catenin complex in cancer has been associated with poor differentiation and acquisition of invasiveness, suggesting a possible role of this protein as an invasion suppressor. In this study, we conducted an immunohistochemical investigation of all components of the E-cadherin/catenin complex in 65 gastric cancer patients. Abnormal expression of E-cadherin and, alpha- and gamma-catenin occurred more frequently in diffuse than in intestinal type of gastric cancer, and correlated with poor differentiation. Abnormal expression of E-cadherin and beta-catenin correlated with poor survival. Abnormal expression of all four components of the complex was associated with poorly differentiated and diffuse-type carcinoma, and poor survival. In the multivariate analysis, abnormal expression of the E-cadherin/catenin complex was not an independent prognostic factor. These results suggest that the E-cadherin/catenin complex may be a useful marker of differentiation and prognosis in gastric cancer. Further studies are warranted to clarify the impact of the E-cadherin/catenin complex on prognostic factor of gastric cancer.

Modulation of biochemical activity of hepatocytes in culture by matrix substratum.

The influence of extra cellular matrix on the biochemical activity of hepatocytes was studied by maintaining rat hepatocytes in primary culture in a serum free medium on different matrix protein substrata or biomatrices prepared from liver, aorta or mammary gland. There was significant difference in the individual protein synthesis and distribution by cells maintained on different substrata. Comparison of the kinetics of synthesis and secretion of albumin by cells maintained on different tissue biomatrix showed that those maintained on hepatic biomatrix synthesized more albumin and retained more of albumin synthetic capacity, when compared to those maintained on aortic and mammary gland biomatrix. Similarly, hepatocytes maintained on hepatic biomatrix synthesized significantly more apo B, the major apo protein of VLDL, than those maintained on heterologous tissue matrix. Induction of tyrosine aminotransferase by dexamethasone and the uptake of [14C]-amino isobutyric acid were found to be maximum in cells maintained on liver biomatrix than the heterologous biomatrix. But cells maintained on hepatic biomatrix incorporated less amounts of radioactivity into total cytoskeletal proteins as well as the individual proteins such as actin and the cytokeratins C8 and C18 while that by cells maintained on aortic biomatrix was significantly high. Quantitative analysis of the relative incorporation of radioactivity into individual cytoskeletal proteins and albumin in pulse labelling studies with cells maintained in culture on different matrix for different lengths of time revealed a reciprocal relationship between these two activities. These results indicate that the substrata with which the cells are in contact influence on a selective basis, the biochemical activity of hepatocytes in primary culture.