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Amplification and Overexpression of TP63 and MYC as Biomarkers for Transition of Cervical Intraepithelial Neoplasia to Cervical Cancer

Zhu, Da MD, PhD*; Jiang, Xiao-Hui MMSc*; Jiang, Yun-Hui BMSc; Ding, Wen-Cheng MD, PhD*; Zhang, Chang-lin MMSc*; Shen, Hui MMSc*; Wang, Xiao-Li MD, PhD*; Ma, Ding MD, PhD*; Hu, Zheng MD, PhD*; Wang, Hui MD, PhD*

International Journal of Gynecological Cancer: May 2014 - Volume 24 - Issue 4 - p 643–648
doi: 10.1097/IGC.0000000000000122
Basic Science

Objective: Biopsy confirmed that cervical intraepithelial neoplasia (CIN) may naturally regress or progress. Currently, the risk assessment for CIN progression to cervical cancer is still not satisfactory in clinical practice. We investigated copy number and protein expression of TP63 and MYC and explored the possibility to use them as progression biomarkers.

Methods: Copy numbers of TP63 and MYC, as well as human papilloma virus (HPV) integration status, were determined by fluorescence in situ hybridization in 39 patients with CIN and 66 patients with cervical cancer. Corresponding protein expressions were analyzed by immunohistochemistry. Receiver operating characteristic curves were used to measure the diagnostic test performance for the detection of cervical cancer from CIN. Sensitivity and specificity values of biomarkers were calculated.

Results: The average copy number and expression of TP63 and MYC, as well as the HPV integration rate, increased in the progression of CIN to cervical cancer. Receiver operating characteristic analysis for detection of cervical cancer resulted in area under the curve (AUC) values of TP63 copy number (AUC, 0.96; 95% confidence interval [CI], 0.91–1.00), MYC copy number (AUC, 0.92; 95% CI, 0.85–0.96), TP63 expression (AUC, 0.73; 95% CI, 0.61–0.85), and HPV-16 integration (AUC, 0.73; 95% CI, 0.60–0.85). MYC expression was not able to statistically distinguish cancer from CIN (P = 0.393). The combinations increased the specificity slightly but not sensitivity. Among them, TP63 amplification showed the best diagnostic performance.

Conclusions: Amplification and overexpression of TP63 and MYC, and HPV integration rate, are associated with the transition of CIN to cervical cancer. Future studies on these biomarkers will help to assess the risk of CIN progression.

*Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; and †Department of Pathology, Jingmen No. 2 People’s Hospital, Jingmen, Hubei, China.

Address correspondence and reprint requests to Zheng Hu, MD, PhD, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. E-mail: huzheng1998@163.com; Hui Wang, MD, PhD, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. E-mail: huit71@sohu.com.

Da Zhu, Xiao-Hui Jiang, and Yun-Hui Jiang contributed equally to this study.

Grant support: National Natural Science Foundation of China (No. 30672227; 30571950; 305005967; 30370657) and the 973 Program of China (No. 2002CB513100).

The authors declare no conflicts of interest.

Received October 29, 2013

Accepted February 11, 2014

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