title: ProEx™ C is a useful ancillary study for grading anal intraepithelial neoplasia alone and in combination with other biomarkers.
abstract: Anal intraepithelial neoplasia (AIN) is a precursor to invasive anal squamous cell carcinoma. Histologic evaluation is hampered by intra- and interobserver variability. Various biomarkers have been investigated to improve the accuracy and reproducibility of diagnosis and grading, but interpretation can be challenging. ProEx™ C is an antibody cocktail for proteins upregulated in cervical intraepithelial neoplasia. This study investigated ProEx™ C's role alone and with p16 and Ki-67 in the diagnosis and grading of AIN. Sixty-seven anal tissue samples (22 AIN I, 25 AIN II/III, and 20 non-dysplastic) were stained for ProEx™ C, Ki-67, and p16. Staining patterns were recorded and correlated with morphologic diagnoses. Considering AIN II/III vs I, full-thickness ProEx™ C staining was more frequent in AIN II/III (p = 0.0373), and showed the highest sensitivity of the biomarkers. In combination with Ki-67, sensitivity was lower, but specificity for AIN II/III rose to 83%. For differentiating non-dysplasia from AIN I, negative ProEx™ C staining correlated with non-dysplasia (p < 0.0001) and had the highest sensitivity (90%). In combination with Ki-67, sensitivity dropped to 80%, but specificity was high (96%). ProEx™ C is useful for diagnosing and grading AIN, performing as well or better than other markers at identifying AIN II/III and non-dysplastic epithelium.
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Brent K
authors.initials: BK
authors.lastname: Larson
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Sambit K
authors.initials: SK
authors.lastname: Mohanty
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Walts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000097:blood / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000097:blood*; D002278:Carcinoma in Situ / Q000097:blood / Q000175:diagnosis*; D005260:Female; D019942:Genes, p16; D006801:Humans; D019394:Ki-67 Antigen / Q000097:blood; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Ki-67; ProEx C; anal intraepithelial neoplasia; immunohistochemistry; p16