Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer

Abstract

E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd-type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells.

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

“…A germline mutation in E-cadherin associated with familial gastric cancer was recently reported in a New Zealand kindred (Guilford et al, 1998). Mutations in α-and β-catenins have not been convincingly demonstrated, but protein expression abnormalities are relatively frequent, and occur in both diffuse and intestinal cancers (Oka et al, 1992;Matsui et al, 1994;Jawhari et al, 1997). We have confirmed a high frequency of expression abnormalities for all three molecules studied.…”

E-cadherin expression in plasmacytoid, signet ring cell and micropapillary variants of urothelial carcinoma: comparison with usual-type high-grade urothelial carcinoma

“…28 Recent studies have demonstrated that loss of E-cadherin immunoreactivity may correlate with a lack of differentiation and aggressive behavior of breast, head and neck, lung, gastric, esophageal, colorectal, prostatic and urothelial carcinomas. [5][6][7]15,[29][30][31][32][33][34][35] Published studies on urothelial carcinoma show that loss of membranous E-cadherin immunoreactivity is strongly correlated with high grade and advanced stage. 8,12,15,[36][37][38] Whether or not loss of E-cadherin is correlated with disease progression or has any prognostic significance has been debated by several investigators.…”

Mechanisms inactivating the gene for E-cadherin in sporadic gastric carcinomas

“…Inactivation of the CDH1 gene and loss of normal E-cad expression were involved more frequently in diffuse type than in intestinal type tumors (88% vs 48%; P = 0.006). However, the percentage of reduction in E-cad expression of GC varies from 17% to 92% in previous reports [8][9][10][11][12][13] Promoter polymorphism Li et al [22] reported that the A allele of the -160C/A promoter polymorphism alters transcriptional binding, resulting in a reduction in transcriptional efficiency of 68% relative to that of the C allele. In our study, there was no significant difference in the frequency of the C/A + A/A genotypes between diffuse and intestinal type tumors.…”

“…E-cad gene (CDH1) is an important putative tumor suppressor gene. In gastric carcinomas (GCs), the reduction in E-cad expression activation of Ecad gene varies from 17% to 92%, and is more frequent in diffuse type than in intestinal type tumors [8][9][10][11][12][13] . Germline mutation of the CDH1 gene is found in all familial GCs [14,15] .…”