Clinical significance of hypoxia-inducible factor-1a messenger RNA expression in locally advanced non-small-cell lung cancer after platinum agent and gemcitabine chemotherapy followed by surgery.

Hypoxia-inducible factor-1a (HIF-1a) is a key regulator of the angiogenic cascade. This study analyzed HIF-1a messenger RNA expression levels using real-time quantitative polymerase chain reaction (PCR) in paraffin-embedded surgical specimens from 54 stage IIB-III patients with non-small-cell lung cancer (NSCLC) treated with induction platinum/gemcitabine followed by surgery between September 1998 and December 2002. Radiographic response was observed in 61% of patients. Median survival was 37.8 months. Forty-five patients with complete resection attained a 52-month median survival, whereas 8 patients with incomplete resection had a 12-month median survival, and 1 unresectable patient had a survival of 14 months. No significant differences were observed in overall survival (OS) or event-free survival (EFS) according to HIF-1a expression levels. Patients were divided into quartiles according to HIF-1a gene expression levels. Median EFS for the 13 patients in the lowest quartile has not been reached yet, whereas median EFS for the 13 patients in the top quartile was 9 months (P = 0.192). Similarly, median OS for the 13 patients in the lowest quartile has not been reached yet, whereas median OS for the 13 patients in the top quartile was 52 months (P = 0.297). The cisplatin/gemcitabine combination is highly active in neoadjuvant treatment. Hypoxia-inducible factor-1a expression levels analyzed by real-time quantitative PCR in surgery specimens after platinum/gemcitabine therapy do not correlate with the outcome of patients with stage II/III NSCLC.