Sec62/Ki67 and p16/Ki67 dual-staining immunocytochemistry in vulvar cytology for the identification of vulvar intraepithelial neoplasia and vulvar cancer: a pilot study
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The aim of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-staining protocol for the simultaneous expression of SEC62 and Ki67 in vulvar liquid-based cytology specimens for the identification of vulvar intraepithelial neoplasia (VIN) and vulvar cancer. In addition, we investigated the p16/Ki67 dual stain, which has already been established in cervical cytology.
Materials and methods
For this pilot study, residual material from liquid-based cytology was collected retrospectively from 45 women. The presence of one or more double-immunoreactive cells was considered as a positive test result for Sec62/Ki67 and p16/Ki67 dual staining. The test results were correlated with the course of histology.
All cases of VIN and vulvar cancer were Sec62/Ki67 and p16/Ki67 dual-stain positive, and normal and low-grade squamous intraepithelial lesions were all negative. The sensitivity of cytology for VIN + cases was 100% (22/22), whereas punch biopsy classified one case of vulvar carcinoma as inflammation. All cases with high-intensity (grades 3 and 4) Sec62 staining in Sec62/Ki67-positive cases were carcinomas.
The results of this study demonstrate that Sec62/Ki67 and p16 Ki67 dual-staining cytology could be a promising adjunctive diagnostic tool for VIN and squamous cell carcinoma, in addition to standard histology.
KeywordsSec62 Ki67 Immunocytochemistry Vulvar cytology Vulvar intraepithelial neoplasia Vulvar cancer
The authors would like to gratefully thank for the excellent work, motivation and enthusiasm of Mrs. Barbara Linxweiler and Mrs. Alice Kunz in the establishment of our dual-staining cytology method.
FZT: conceptualization, data curation, methodology, project administration, validation, writing the original draft, and review and editing. JCR: review and editing. FB: visualization, review and editing. IJ-B: review and editing, E-FS: review and editing, RMB: review and editing. G-PB: review and editing. BS: review and editing. ML: supervision, methodology, project administration, validation, review and editing.
Compliance with ethical standards
Conflict of interest
Ferenc Zoltan Takacs and Maximilian Linxweiler have a pending patent application. Patent applicant: University of Saarland. Names of inventors: Ferenc Zoltan Takacs, Maximilian Linxweiler. Application number: LU100824. All other authors declare no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of Saarland (No: 183/17). Written informed consent was obtained from all patients prior to inclusion.
The study was approved by the Ethics Committee of Saarland (No: 183/17). Written informed consent was obtained from all patients prior to inclusion.
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