Dual-Stained Cervical Cytology and Histology with Claudin-1 and Ki67
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Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study. Parallel p16/Ki67 (CINtec® PLUS) and CLDN1/Ki67 dual-stained cytology and histology were performed and compared. p16/Ki67 immunoreaction showed positivity in 317 out of 1596 smears with negativity in 1072 and unacceptable reactions in 207 samples. CLDN1/Ki67 dual staining was positive in 200 of 1358 samples, negative in 962, whereas 196 smears could not be evaluated due to technical reasons. Considering the high-grade squamous intraepithelial lesion cytology as gold standard, sensitivity of CLDN1/Ki67 reaction was 76%, specificity was 85.67%, while for p16/Ki67 sensitivity was 74% and specificity was 81.38%. Comparison of CLDN1/Ki67 and p16/Ki67 dual stainings showed the results of the two tests not to be significantly different. Analysing histological slides from 63 cases, the results of the two tests agreed perfectly. As conclusion the sensitivity and specificity proved to be similar using p16/Ki67 and CLDN1/Ki67 double immunoreactions both on LBC samples and on histological slides.
KeywordsCervical cancer Claudin-1/Ki67 immunochemistry p16/Ki67 reaction Claudins
TSz performed and evaluated the immunreactions and statistics, ÁG and AM collected the clinical samples and data, BJ and AKi evaluated the cytology, ZsS and GS designed and coordinated the study and wrote the manuscript. AKo and MB are clinical experts of the TRACE clinical study (Cellcall). TT is the inventor of the HPV detection technology applied in the CONFIDENCE HPV™ (NEUMANN Diagnostics) testing. CsJ was former head of the TRACE clinical study (Cellcall). ZsS accepts full responsibility for the work. All authors have read and approved the final manuscript.
This work was supported by grant #NKFP_07_2-SPE-SAFE, Jedlik Ányos 2. subprogram KMR_12–1–2012-0032 by the Hungarian National Research and Development Fund and grant #OTKA PD105019 by the Hungarian National Research Foundation.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest with respect to the research, authorship, and/or publication of this article.
AKo is an employee of Cellcall and NEUMANN. MB receives consultancy fees from Cellcall and NEUMANN, she is an employee of SYNLAB GenoID Laboratory, which participated in the TRACE clinical study (all related expenses were charged to Cellcall and NEUMANN). TT is a part time employee of Cellcall, he receives consultancy fees from NEUMANN, he is minority owner of NEUMANN, the inventor of the HPV detection technology described in the manuscript covering which Cellcall submitted a patent application (license now owned by NEUMANN Diagnostics Ltd.); he is a part time employee of SYNLAB GenoID Laboratory. CsJ was a former employee of Cellcall. MNy is an employee of Cellcall and NEUMANN.
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