Clinical Significance of Hypoxia-Inducible Factor-1α Messenger RNA Expression in Locally Advanced Non-Small-Cell Lung Cancer After Platinum Agent and Gemcitabine Chemotherapy Followed by Surgery

Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of the angiogenic cascade. This study analyzed HIF-1α messenger RNA expression levels using real-time quantitative polymerase chain reaction (PCR) in paraffinembedded 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-1α expression levels. Patients were divided into quartiles according to HIF-1α 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-1α 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.