HGM2002 Poster Abstracts: 8. Disease Mechanisms
POSTER NO: 416
Defective expression of E-cadherin in non-small cell lung cancer
1Qingyan Fei, 2Xiaofeng Chen, 1Hongtao Zhang, 1Jiucun Wang, 1Rongmei Zhang, 3Weiqing Xu, 1Zhen Zhang, 1Wei Zou, 1Kangyu Zhang, 1Qingyuan Qi, 1Minghua Wang, 1Zewei Luo
Cadherins are transmembrane cell adhesion molecules (CAMs) that mediate cell-cell interactions and are crucial for the formation of intercellular junctional complexes and the establishment of cell polarity in epithelial cells. E-cadherin is the family member studied probably in the most detail. Multiple studies have suggested that loss of E-cadherin expression is responsible for acquisition of invasive potential in various epithelial-derived tumors. However, the underlying genetic abnormalities are still under investigation. To find out whether E-cadherin inactivation may be related to the pathogenesis of non-small cell lung cancer (NSCLC), we undertook the present immunohistochemical and molecular biology study of E-cadherin gene in 40 resection specimens of NSCLC and the corresponding paracarcinoma controls. For immunohistochemical detection of E-cadherin, the well-characterized HECD-1 monoclonal antibody was employed. A semi-quantitative approach was used for scoring the immunostaining. Strongly positive (++) tumors were classified as a type of preserved E-cadherin expression, while the others (+,-) were classified as a type of reduced E-cadherin expression. In agreement with previous reported data, we also observed decreased expression of E-cadherin proteins in NSCLC. In the search for mechanisms that might be involved in the down-regulation of E-cadherin expression, we used polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) technique to look for mutations in the entire coding sequence of E-cadherin gene. Only in one amplicon were aberrant bands detected. Sequencing of the amplicon revealed a known variation (GCC-GCT; codon 692; exon 13) and the results of restriction endonuclease digestion showed that the frequency of the transition was 35.5% in tumor samples. The 40 corresponding paracarcinoma tissues were also studied and no differences were detected between the tumor samples and the corresponding normal controls. The findings confirmed that the variation was only a polymorphism instead of a somatic mutation in the Chinese population under investigation. In conclusion, our findings support the hypothesis that alterations in expression, and particularly loss of expression, of E-cadherin may play a role in the development of the malignant phenotype in NSCLC. However, the alterations of E-cadherin gene are not involved in the pathogenesis and clinical progression of NSCLC and do not appear to be responsible for reduced expression of E-cadherin gene.
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