Study on expression and methylation of caveolin 1 gene in non-small cell lung cancers

Abstract

To study the methylation of CpG islands in the promoter region, expression of caveolin 1 (Cav-1) gene and their clinical significance in non-small cell lung cancers (NSCLC). Immunohistochemistry and quanta Qd600 staining were used to detect the expression of Cav-1 in tissues from benign lung lesions (n = 17) and NSCLC (n = 123). DNA was treated with sodium bisulfite and the Cav-1 promoter region was screened using methylation-specific polymerase chain reaction for the possible methylation sites. Cav-1 protein was highly expressed in cytoplasm and cell membrane of normal bronchial epithelium, alveolar epithelium, endothelial cells, fibroblasts and smooth muscle cells. The expression rates of Cav-1 protein were 100% (17/17) in the control group and 43.1% (53/123) in the NSCLC group (P = 0.001). Amongst the NSCLC group, there was no statistically significant difference in Cav-1 protein expression in different histologic types (P = 0.552) and tumor grades (P = 0.160). On the other hand, Cav-1 protein immunoreactivity was remarkably higher in advanced tumor stage: 72.7% in stage III A + III B, compared with 9.4% in stage I A + I B and 38.3% in stage II A + II B (P = 0.001). The expression rate of Cav-1 protein in the NSCLC cases with lymph node metastasis was 53.6%, compared with 20.5% in those without nodal involvement (P = 0.001). DNA from 40 NSCLC cases with negative Cav-1 protein expression and 12 cases of peritumoral lung tissues were extracted. Methylation in the promoter region of Cav-1 gene was not detected in lung cancer or peritumoral tissues. High expression of Cav-1 protein is respected of the aggressive clinical behavior and advanced tumor stage. Loss of Cav-1 protein expression seems not correlated to the methylation status in the promoter region of Cav-1 gene.