E-cadherin expression in primary and metastatic gastric cancer : down-regulation correlates with cellular dedifferentiation and glandular disintegration

• Published in: Cancer research (Chicago, Ill.) Vol. 53; no. 7; pp. 1690 - 1695
• Main Authors: MAYER, B, JOHNSON, J. P, LEITL, F, JAUCH, K. W, HEISS, M. M, SCHILDBERG, F. W, BIRCHMEIER, W, FUNKE, I
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.1993
• Subjects: Biological and medical sciences; Cadherins - metabolism; Cell Differentiation; Down-Regulation; Gastric Mucosa - metabolism; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Medical sciences; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Immunohistochemistry; Stomach; Carcinoma; Cell adhesion molecule; Malignant tumor; Potential; Gene expression; Cadherin; Adhesion; Pathology; Digestive diseases; Advanced stage; Metastatic; Gastric disease
• ISSN: 0008-5472; 1538-7445

Expression of the epithelial cell adhesion molecule E-cadherin in primary and metastatic gastric carcinoma was examined using immunohistochemical analyses. Compared to normal mucosa, 92% of the primary tumors (n = 60) showed reduced E-cadherin expression, suggesting that down-regulation of this cell adhesion molecule is a common early event in gastric tumorigenesis. No significant correlation was found between E-cadherin expression and tumor diameter, lymphatic vessel invasion, Borrmann classification, lymph node status, or manifest metastases. Although advanced tumors (tumor stage 3/4) showed a loss of E-cadherin-positive cells (< or = 50% cells/lesion, P = 0.0168), the most significant correlation was observed between low E-cadherin expression and cellular dedifferentiation (grading 3/4, P = 0.0001) and disintegration of tissue architecture (Lauren and WHO classifications, P = 0.0001). Low E-cadherin expression (< or = 50% cells/lesion) was associated with tumor recurrence (P = 0.0013) and mortality (P = 0.0246). E-cadherin expression in metastatic lesions (n = 58) also correlated with the degree of glandular differentiation (P = 0.0001). Significant correlation (rs = 0.686) was observed between E-cadherin expression in primary and metastatic lesions from individual patients (n = 39). However, while metastases derived from E-cadherin-negative tumors remained negative, those originating from E-cadherin-positive tumors frequently demonstrated increased levels of expression. Evaluation of multiple metastases in 11 patients revealed uniformly strong E-cadherin expression in liver metastases, suggesting a possible regulatory role of the microenvironment.