Original ArticlesUtility of CK7 Versus p16 as a Prognostic Biomarker in CIN 2Umphress, Brandon MD*; Sanchez, Beatriz MD†; Paintal, Ajit MD*; Nayar, Ritu MD*; Maniar, Kruti P. MD*Author Information *Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL †Department of Pathology, Indiana University Health Bloomington Hospital, Bloomington, IN Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Kruti P. Maniar, MD, Department of Pathology, Northwestern University, Feinberg Pavilion, 7-332, 251 E Huron St., Chicago, IL 60641 (e-mail: Kruti.Maniar@northwestern.edu). The American Journal of Surgical Pathology: April 2018 - Volume 42 - Issue 4 - p 479-484 doi: 10.1097/PAS.0000000000001032 Buy Metrics Abstract Cervical intraepithelial neoplasia (CIN) 2 is an equivocal diagnosis, with p16 immunohistochemical positivity currently recommended for diagnostic confirmation. Biomarkers characteristic of squamocolumnar junction cells were recently found to be positive in almost all CIN 2 and CIN 3. CIN 1 lesions which express squamocolumnar junction markers (in particular cytokeratin 7 [CK7]) are associated with a higher rate of subsequent high-grade squamous intraepithelial lesion, suggesting that CK7 may be a useful prognostic biomarker for CIN 1. We sought to determine the utility of CK7 as a prognostic biomarker in the setting of morphologic CIN 2, and to compare this to the utility of p16 in this setting. We performed CK7 immunohistochemical on 116 cases originally diagnosed as CIN 2. Of these, 68.1% were p16+ and 90.5% were CK7+. A total of 19.5% of patients had a subsequent diagnosis of CIN 3 on biopsy or excision; the index CIN 2 lesion was CK7+ in all of these cases (sensitivity 100%) and p16+ in all but 1 (21/22; sensitivity 95.5%). The specificity of p16 (37.4%) and CK7 (8.0%) for predicting subsequent CIN 3 were significantly different (P<0.001). While p16 expression was significantly associated with subsequent CIN 3 (P=0.002), CK7 expression was not (P=0.202). We conclude that CK7, unlike p16, is not useful as a prognostic biomarker in CIN 2. While it is still promising as a prognostic marker in CIN 1, additional studies are needed to determine optimal staining/interpretation criteria. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.