@article{3082697, title = "Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas", author = "Garinis, GA and Menounos, PG and Spanakis, NE and Papadopoulos, K and and Karavitis, G and Parassi, I and Christeli, E and Patrinos, GP and and Manolis, EN and Peros, G", journal = "JOURNAL OF PATHOLOGY", year = "2002", volume = "198", number = "4", pages = "442-449", publisher = "John Wiley & Sons, Ltd", issn = "0022-3417", doi = "10.1002/path.1237", keywords = "colorectal cancer; E-cadherin; methylation; immunohistochemistry; RT-PCR", abstract = "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 F-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, chi2) 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, respective]),. 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 epigenctically mediated loss of E-cadherin function in these carcinomas. Copyright (C) 2002 John Wiley Sons, Ltd." }