title: E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration.
abstract: 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.
authors.affiliation: Department of Surgery, University of Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Mayer
authors.forename: J P
authors.initials: JP
authors.lastname: Johnson
authors.forename: F
authors.initials: F
authors.lastname: Leitl
authors.forename: K W
authors.initials: KW
authors.lastname: Jauch
authors.forename: M M
authors.initials: MM
authors.lastname: Heiss
authors.forename: F W
authors.initials: FW
authors.lastname: Schildberg
authors.forename: W
authors.initials: W
authors.lastname: Birchmeier
authors.forename: I
authors.initials: I
authors.lastname: Funke
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D015820:Cadherins