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Hypermethylation‐associated transcriptional silencing of E‐cadherin in primary sporadic colorectal carcinomas
Author(s) -
Garinis George A,
Menounos Panayiotis G,
Spanakis Nick E,
Papadopoulos Kostas,
Karavitis George,
Parassi Ismailou,
Christeli Evangelia,
Patrinos George P,
Manolis Evangelos N,
Peros George
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1237
Subject(s) - loss of heterozygosity , immunohistochemistry , methylation , biology , gene silencing , microbiology and biotechnology , pathology , cadherin , dna methylation , gene expression , allele , gene , cancer research , medicine , genetics , cell
Loss of E (epithelial)‐cadherin expression has been previously documented in sporadic colorectal carcinomas (SCRCs), but not as a consequence of mutations or allelic loss. In this study, the methylation status of the E‐cadherin promoter was examined by utilizing the methylation‐specific polymerase chain reaction (MSP) assay in 63 primary SCRCs and paired adjacent normal tissues. This was correlated with E‐cadherin expression at both the RNA and the protein levels using multiplex reverse transcription (RT)‐PCR and immunohistochemistry (IHC), respectively. Data were associated with the patients' clinicopathological features. Methylated alleles were present in 34/61 (56%) of the samples examined. Decreased E‐cadherin mRNA expression was demonstrated in 29/61 carcinomas (47.5%) and was significantly associated with lymph node (LN) metastases ( p = 0.03, Kruskal–Wallis) and tumour stages Astler‐Coller B1 and B2 ( p = 0.01, chi 2 ). E‐cadherin IHC expression was significantly associated with the absence of LN metastases ( p = 0.01, chi 2 ) and tumour stages Astler‐Coller B1 and B2 ( p = 0.002, Kruskal–Wallis) in 28/63 (44.4%) of the samples examined. Twenty‐three out of 29 (79.3%) samples with decreased mRNA expression and 20/33 (60.6%) with detected protein expression revealed methylated ( p = 0.03, Kruskal–Wallis) and unmethylated ( p = 0.01, Kruskal–Wallis) alleles, respectively. In agreement with previous work demonstrating that somatic mutations and loss of heterozygosity of the E‐cadherin gene are rare or absent in the majority of SCRCs studied so far, this study reports a consistent and uniform decrease or absence of E‐cadherin expression, associated with aberrant methylation, in the majority of carcinomas examined, suggesting an epigenetically mediated loss of E‐cadherin function in these carcinomas. Copyright © 2002 John Wiley & Sons, Ltd.