Amplification and overexpression of TP63 and MYC as biomarkers for transition of cervical intraepithelial neoplasia to cervical cancer.

Abstract

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.

• Authors: Da Zhu, Xiao-Hui Jiang, Yun-Hui Jiang, Wen-Cheng Ding, Chang-Lin Zhang, Hui Shen, Xiao-Li Wang, Ding Ma, Zheng Hu, Hui Wang
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 24 Issue 4 Pg. 643-8 (May 2014) ISSN: 1525-1438 [Electronic] England
• PMID: 24662128 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• TP63 protein, human
• Transcription Factors
• Tumor Suppressor Proteins

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Squamous Cell (metabolism, pathology, surgery)
• Female
• Follow-Up Studies
• Gene Amplification
• Humans
• Immunoenzyme Techniques
• In Situ Hybridization, Fluorescence
• Middle Aged
• Neoplasm Staging
• Prognosis
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• ROC Curve
• Transcription Factors (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)
• Uterine Cervical Neoplasms (metabolism, pathology, surgery)
• Uterine Cervical Dysplasia (metabolism, pathology, surgery)