Hypoxia-inducible factor-1α and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: A retrospective study

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Abstract

Hypoxia-inducible factor-1α (HIF-1α), which plays an essential role in the adaptive response of cells to hypoxia, is associated with aggressive tumor behavior. Furthermore, a relationship between excision repair cross-complementing 1 (ERCC1) expression and platinum resistance has been reported in patients with various malignancies. The aim of this study was to investigate the expression of HIF-1α and ERCC1 and to elucidate the clinical significance of their expression in patients with small cell lung cancer (SCLC) treated with front-line platinum-based chemotherapy. Methods: SCLC biopsy samples were obtained before front-line platinum-based chemotherapy from 111 patients with SCLC (limited disease, 29; extensive disease [ED], 82) between January 2002 and December 2009 at Gyeongsang National University Hospital. The expression levels of HIF-1α and ERCC1 were assessed by immunohistochemistry. Results: High expression levels of ERCC1 and HIF-1α were observed in 49 (44.1%) and 71 (64.0%) of 111 patients, respectively. Expression of ERCC1 and HIF-1α was not significantly associated with age, sex, Eastern Cooperative Oncology Group performance status, weight loss, or response to treatment, regardless of stage. In ED-SCLC, low expression in the HIF-1α group showed statistically better survival compared with high expression in the HIF-1α group (p = 0.018). Multivariate analysis revealed that response to front-line platinum-based chemotherapy (p < 0.001), good Eastern Cooperative Oncology Group performance status (0-1) (p = 0.002), and low expression of HIF-1α (p = 0.004) were independent predictors of better overall survival in ED-SCLC. Conclusions: Low expression of HIF-1α may be a useful predictor of better overall survival in ED-SCLC patients treated with front-line platinum-based chemotherapy. Copyright © 2012 by the International Association for the Study of Lung Cancer.

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Lee, G. W., Go, S. I., Cho, Y. J., Jeong, Y. Y., Kim, H. C., Duk Lee, J., … Lee, J. S. (2012). Hypoxia-inducible factor-1α and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: A retrospective study. Journal of Thoracic Oncology, 7(3), 528–534. https://doi.org/10.1097/JTO.0b013e3182417830

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