Unusual expression and molecular mechanisms of E-cadherin, beta-catenin in correlation with clinicopathologic parameters in neuroblastoma.
- Author:
Xiang-ru WU
1
;
Ming-hua ZHU
;
Zhong-de ZHANG
;
Min-zhi YIN
;
Zheng-jun XI
;
Feng-ying ZHANG
;
Wen-zhu ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Cadherins; genetics; metabolism; Child; Child, Preschool; CpG Islands; genetics; DNA Methylation; DNA, Neoplasm; genetics; Exons; Female; Ganglioneuroblastoma; genetics; metabolism; pathology; Gene Rearrangement; Humans; Infant; Lymphatic Metastasis; Male; Mediastinal Neoplasms; genetics; metabolism; pathology; Neuroblastoma; genetics; metabolism; pathology; Point Mutation; Promoter Regions, Genetic; genetics; Retroperitoneal Neoplasms; genetics; metabolism; pathology; Sequence Analysis, DNA; beta Catenin; genetics; metabolism
- From: Chinese Journal of Pathology 2007;36(3):155-159
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the expression of E-cadherin and beta-catenin in neuroblastomas of various degrees of differentiation, and to investigate their molecular mechanisms in correlation with clinicopathologic parameters.
METHODSImmunohistochemistry EnVision method was used to detect E-cadherin and beta-catenin expression in 90 paraffin-embedded tissue samples of neuroblastomas. The methylation status of CpG islands of E-cadherin promoter was investigated by MSP in 7 fresh tissue and 24 paraffin-embedded tissue samples. The mutation status of exon 3 of beta-catenin gene was studied by PCR in 7 fresh tissue samples. Statistical analysis of the data was performed by SPSS software.
RESULTSE-cadherin and beta-catenin were abnormally expressed in neuroblastomas in general. The expression of beta-catenin in well-differentiated neuroblastoms was markedly higher (47/70, 67.1%) than that of the poorly differentiated tumors (8/20, 40.0%). There was a markedly decreased expression of both genes in tumors with lymph node metastasis than those without. Demethylation was seen in some regions of the promoter of E-cadherin in 31 cases of nuroblatomas. PCR of the exon 3 of beta-catenin followed by DNA sequencing demonstrated rearrangements and mutations in 7 cases, including 2 cases harboring identical point mutation at gene position 27184, leading to a T-->A alteration.
CONCLUSIONSThe abnormal over-expression of E-cadherin in neuroblastomas is independent of the methylation status of their promoter sequences. The abnormal expression of beta-catenin may be related to mutational changes at exon 3 of the gene.