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Relationship between E‐cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl‐2 expression and Ki‐67 staining in diffuse‐type gastric carcinoma
Author(s) -
Fricke Elena,
Keller Gisela,
Becker Ingrid,
Rosivatz Erika,
Schott Christina,
Plaschke Susanne,
Rudelius Martina,
Hermannstädter Christine,
Busch Raymonde,
Höfler Heinz,
Becker KarlFriedrich,
Luber Birgit
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10879
Subject(s) - cadherin , mutation , biology , exon , cancer research , gene mutation , pathology , immunohistochemistry , microbiology and biotechnology , carcinoma , cancer , gene , cell , genetics , medicine , immunology
Abstract E‐cadherin mutations are found in 50% of diffuse‐type gastric carcinoma, but not in intestinal gastric carcinoma. Because cell–cell adhesion mediated by E‐cadherin plays an important role in epithelial cell survival, E‐cadherin mutations could alter the apoptotic behavior of tumor cells. p53 and Bcl‐2 family members are also important regulators of cellular apoptosis. This is the first study that investigates the relationship between E‐cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl‐2 expression, and Ki‐67 expression in diffuse‐type gastric carcinoma (24 cases, E‐cadherin mutation status: wild‐type in 8 patients and mutant in 16 patients). The mutation status of exons 5–8 of p53 was analyzed by denaturing high pressure liquid chromatography (DHPLC) in formalin‐fixed, paraffin‐embedded tumor sections, followed by direct sequencing of cases with aberrant chromatographic patterns. p53 mutations were found in 1 of 8 tumors without E‐cadherin mutation (12.5%) and in 1 of 16 tumors with E‐cadherin mutation (6.3%), a difference that was not statistically significant ( p = 1.00). p53 accumulation was found in 8 of 24 tumors (33.3%) by immunohistochemical staining. p53 accumulation was significantly more frequent in tumors without E‐cadherin mutations (5 of 8 tumors, 62.5%) than in gastric carcinoma tissues with E‐cadherin mutations (3 of 16 tumors, 18.8%, p = 0.03). Bcl‐2 staining was not observed in gastric carcinoma cells without E‐cadherin mutations, but was detectable in 5 of 16 tumors with E‐cadherin mutations (31.3%), a difference that was not statistically significant ( p = 0.13). No relationship was observed between Ki‐67 staining and the E‐cadherin mutation status ( p = 1.00). These data suggest that the presence of E‐cadherin mutations can significantly alter the accumulation of the apoptose‐regulating p53 protein, whereas no correlation with the p53 mutation status or with Ki‐67 staining was observed. © 2002 Wiley‐Liss, Inc.