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Overexpression of Hypoxia-Inducible Factor-1α Is a Predictor of Poor Prognosis in Cervical Cancer: A Clinicopathologic Study and a Meta-analysis

Huang, Miaoling MD*; Chen, Qing MD*; Xiao, Jianpeng MD; Yao, Tingting MD, PhD*; Bian, Lijuan MD; Liu, Changhao MD*; Lin, Zhongqiu MD*

International Journal of Gynecological Cancer: July 2014 - Volume 24 - Issue 6 - p 1054–1064
doi: 10.1097/IGC.0000000000000162
Cervical Cancer

Background Published data on the prognostic value of hypoxia-inducible factor-1α (HIF-1α) expression in cervical cancer are conflicting and heterogeneous. We aimed to derive a more precise estimation of them.

Methods We conducted a clinicopathologic study in 74 patients with early-stage cervical cancer treated through surgery and performed a meta-analysis among patients with cervical cancer of all stages to estimate the prognostic importance of HIF-1α expression for disease-free survival (DFS) and overall survival (OS). Expression of HIF-1α was evaluated through immunohistochemistry.

Results A positive nuclear expression of HIF-1α was found in 94.6% of all specimens. There were significant associations between HIF-1α expression and International Federation of Gynecology and Obstetrics stage (P = 0.024), tumor size (P = 0.003), and anemia (P = 0.010), respectively. Log-rank tests revealed significant correlations between HIF-1α expression, International Federation of Gynecology and Obstetrics stages, tumor grade, tumor size and DFS/OS, respectively. The multivariate Cox regression analyses revealed HIF-1α overexpression and high tumor grade to be independent predictors for impaired DFS (HIF-1α overexpression: hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.10–6.47; high tumor grade: HR, 5.56; 95% CI, 1.47–21.13) and OS (HIF-1α overexpression: HR, 2.57; 95% CI, 1.06–6.23; high tumor grade: HR, 6.23; 95% CI, 1.49–25.97). The results of 10 studies indicated that HIF-1α overexpression predicted poor DFS (HR, 1.98; 95% CI, 1.22–3.21) and OS (HR, 2.58; 95% CI, 1.86–3.56) for cervical cancer.

Conclusions The present clinicopathologic study and meta-analysis showed that HIF-1α overexpression is associated with poor survival of cervical cancer and emphasized the importance of HIF-1α as a predictor for cervical cancer.

Supplemental digital content is available in the text.

*Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; †Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention; and ‡Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Address correspondence and reprint requests to Qing Chen, MD, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yanjiang Road 107, Guangzhou, China, 510120. E-mail: sumsqing@21cn.com.

Supported by Guangdong Province Medical Science Technology grant (B2013118) and Guangdong Pharmaceutical Association Fund (Bristol-Myers Squibb Fund) (2012D04).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.ijgc.net).

Received December 31, 2013

Accepted April 1, 2014

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.