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 suppre ssor gene, identified in a region of frequent loss of heterozygosity on chr omosome 17p13.3, which is telomeric from TP53 and often deleted in surgical ly resected lung cancers. To determine the significance of HIC-1 in lung ca ncer, we assessed its expression status and prognostic association in 47 ad enocarcinomas and squamous cell carcinomas. Materials and Methods: RNA was extracted from tumors and corresponding normal tissues of surgically resect ed lungs, and the amount of HIC-1 mRNA was determined by means of semi-quan titative reverse transcriptase-polymer ase chain reaction. Results: HIC-1 e xpression in tumors was less than that in normal lung tissues in 40 of 47 p atients (85%), indicating frequent partial silencing. Median tumor/normal l ung tissue (TIL) ratios for HIC-1 expression were 0.51 and 0.75 for adenoca rcinomas and squamous cell carcinomas, respectively. No significant differe nce of median TIL 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 TIL ratios (<0.5) were significantly associated with short survival (P=0.03 4), nit 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.