Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3082697 36 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Hypermethylation-associated transcriptional silencing of E-cadherin in
primary sporadic colorectal carcinomas
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Έτος δημοσίευσης:
2002
Συγγραφείς:
Garinis, GA
Menounos, PG
Spanakis, NE
Papadopoulos, K and
Karavitis, G
Parassi, I
Christeli, E
Patrinos, GP and
Manolis, EN
Peros, G
Περιοδικό:
JOURNAL OF PATHOLOGY
Εκδότης:
John Wiley & Sons, Ltd
Τόμος:
198
Αριθμός / τεύχος:
4
Σελίδες:
442-449
Λέξεις-κλειδιά:
colorectal cancer; E-cadherin; methylation; immunohistochemistry; RT-PCR
Επίσημο URL (Εκδότης):
DOI:
10.1002/path.1237
Το ψηφιακό υλικό του τεκμηρίου δεν είναι διαθέσιμο.