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Overexpression of p16 INK4A in liquid‐based specimens (SurePath™) as marker of cervical dysplasia and neoplasia
Author(s) -
Saqi Anjali,
Pasha Theresa L.,
McGrath Cindy M.,
Yu Gordon H.,
Zhang Paul,
Gupta Prabodh
Publication year - 2002
Publication title -
diagnostic cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.417
H-Index - 65
eISSN - 1097-0339
pISSN - 8755-1039
DOI - 10.1002/dc.10205
Subject(s) - medicine , pathology , dysplasia , squamous intraepithelial lesion , cervical intraepithelial neoplasia , papanicolaou stain , staining , immunohistochemistry , cervical cancer , antibody , intraepithelial neoplasia , cancer , cancer research , immunology , prostate cancer
Abstract Human papillomavirus (HPV) is recognized as a causal agent for cervical carcinomas. Assimilation of HPV oncogenes E6 and E7 into the host DNA promotes upregulation of cyclin dependent kinase inhibitor (CDKI) p16 INK4A , detectable by monoclonal antibody in the developing cervical cancer cells. The aim of this study was to 1) develop a protocol for p16 INK4A immunocytochemical staining on SurePath™ preparations, and 2) determine its utility as an HPV marker on a spectrum of cervical reactive and neoplastic lesions. Seventy‐two specimens consisting of 28 nonneoplastic/nondysplastic cases (NN), one reactive glandular cells (RGC), 27 low‐grade squamous intraepithelial lesions (LSIL), 10 high‐grade squamous intraepithelial lesions (HSIL), one squamous cell carcinoma (SCCA), four atypical glandular cells (AGUS), and two adenocarcinomas (ADCA) were reprepped by SurePath™ and antibody to p16 INK4A applied at 1:100 dilution using the Dako Envision + System on the Dako Autostainer. Expression of p16 INK4A within the nucleus principally and cytoplasm of at least 10–15 cells was considered positive. All initial Papanicolaou‐stained discrepant cases (p16 INK4A positivity of NN and RGC cases and lack of reactivity in LSIL, HSIL, and AGUS) were reviewed. Nine of ten (90%) HSIL, one (100%) SCCA, 21/27 (78%) LSIL, and some reactive and inflammatory specimens demonstrated the presence of p16 INK4A . Reevaluation of discrepant cases revealed that several were underinterpreted (four NN were LSIL, one RGC was AGUS) or overinterpreted (one LSIL was NN). Following reassessment, false‐positive staining was present in only 1/25 (1.4%) NN. Six of 30 (20%) LSIL lacked p16 INK4A positivity. One of 10 (10%) HSIL had no staining. Two of four AGUS did not react with p16 INK4A antibody. Both SCCA (1) and ADCA (2) had positive expression. This study confirms the intimate relationship between p16 INK4A and HPV cytopathic effect. The p16 INK4A immunocytochemical stain can be applied to liquid‐based cervical preparations. This technique offers a more objective approach to deciphering “gray areas” of gynecologic cytopathology. Diagn. Cytopathol. 2002;27:365–370. © 2002 Wiley‐Liss, Inc.