Reduced HIC-1 gene expression in non-small cell lung cancer and its clinical significance

Background: HIC-1 (hypermethylated in cancer-1) is a candidate tumor suppressor gene, identified in a region of frequent loss of heterozygosity on chromosome 17p13.3, which is telomeric from TP53 and often deleted in surgically resected lung cancers. To determine the significance of HIC-1 in lung cancer, we assessed its expression status and prognostic association in 47 adenocarcinomas and squamous cell carcinomas. Materials and Methods: RNA was extracted from tumors and corresponding normal tissues of surgically resected lungs, and the amount of HIC-1 mRNA was determined by means of semi-quantitative reverse transcriptase-polymerase chain reaction. Results: HIC-1 expression in tumors was less than that in normal lung tissues in 40 of 47 patients (85%), indicating frequent partial silencing. Median tumor/normal lung tissue (T/L) ratios for HIC-1 expression were 0.51 and 0.75 for adenocarcinomas and squamous cell carcinomas, respectively. No significant difference of median T/L ratio was observed between the two histological types, or among clinical stages of the patients. However, the reduced expression of HIC-1 gene in the tumor had a direct link with the clinical outcome: lower T/L ratios (<0.5) were significantly associated with short survival (P=0.034), an association also observed in cases restricted to stage I (P=0.047). Conclusions: The results suggest that low HIC-1 expression is involved in malignant progression of non-small cell lung cancer.