[Unusual expression and molecular mechanisms of E-cadherin, beta-catenin in correlation with clinicopathologic parameters in neuroblastoma].
OBJECTIVE
To 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.


METHODS
Immunohistochemistry 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.


RESULTS
E-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.


CONCLUSIONS
The 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.
Wu
Xiang-ru
XR
Department of Pathology, Xinhua Hospital, Medical College, Shanghai Jiaotong University, Shanghai 200092, China.
Zhu
Ming-hua
MH
Zhang
Zhong-de
ZD
Yin
Min-zhi
MZ
Xi
Zheng-jun
ZJ
Zhang
Feng-ying
FY
Zhang
Wen-zhu
WZ
D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005260:Female; D018305:Ganglioneuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D008207:Lymphatic Metastasis; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012186:Retroperitoneal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017422:Sequence Analysis, DNA; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D004273:DNA, Neoplasm; D051176:beta Catenin