title: 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.affiliation: *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.
authors.forename: Da
authors.initials: D
authors.lastname: Zhu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Jiang
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Jiang
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Ding
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012372:ROC Curve; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins