{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:19:47Z","timestamp":1760242787475},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,11,20]],"date-time":"2015-11-20T00:00:00Z","timestamp":1447977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2016,3]]},"abstract":"Anal intraepithelial neoplasia (AIN<\/jats:styled-content>) is a precursor to invasive anal squamous cell carcinoma. Histologic evaluation is hampered by intra\u2010 and interobserver variability. Various biomarkers have been investigated to improve the accuracy and reproducibility of diagnosis and grading, but interpretation can be challenging. ProEx\u2122<\/jats:sup> C is an antibody cocktail for proteins upregulated in cervical intraepithelial neoplasia. This study investigated ProEx\u2122<\/jats:sup> C's role alone and with p16 and Ki\u201067 in the diagnosis and grading of AIN<\/jats:styled-content>. Sixty\u2010seven anal tissue samples (22 AIN<\/jats:styled-content> I, 25 AIN II<\/jats:styled-content>\/III<\/jats:styled-content>, and 20 non\u2010dysplastic) were stained for ProEx\u2122<\/jats:sup> C, Ki\u201067, and p16. Staining patterns were recorded and correlated with morphologic diagnoses. Considering AIN II<\/jats:styled-content>\/III<\/jats:styled-content> vs I, full\u2010thickness ProEx\u2122<\/jats:sup> C staining was more frequent in AIN II<\/jats:styled-content>\/III<\/jats:styled-content> (p = 0.0373), and showed the highest sensitivity of the biomarkers. In combination with Ki\u201067, sensitivity was lower, but specificity for AIN II<\/jats:styled-content>\/III<\/jats:styled-content> rose to 83%. For differentiating non\u2010dysplasia from AIN<\/jats:styled-content> I, negative ProEx\u2122<\/jats:sup> C staining correlated with non\u2010dysplasia (p < 0.0001) and had the highest sensitivity (90%). In combination with Ki\u201067, sensitivity dropped to 80%, but specificity was high (96%). ProEx\u2122<\/jats:sup> C is useful for diagnosing and grading AIN<\/jats:styled-content>, performing as well or better than other markers at identifying AIN II<\/jats:styled-content>\/III<\/jats:styled-content> and non\u2010dysplastic epithelium.<\/jats:p>","DOI":"10.1111\/apm.12481","type":"journal-article","created":{"date-parts":[[2015,11,21]],"date-time":"2015-11-21T04:34:45Z","timestamp":1448080485000},"page":"175-180","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["ProEx\u2122<\/sup> C is a useful ancillary study for grading anal intraepithelial neoplasia alone and in combination with other biomarkers"],"prefix":"10.1111","volume":"124","author":[{"given":"Brent K.","family":"Larson","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cedars\u2010Sinai Medical Center Los Angeles CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sambit 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