title: A pilot evaluation of a novel immunohistochemical assay for topoisomerase II-alpha and minichromosome maintenance protein 2 expression (ProEx C) in cervical adenocarcinoma in situ, adenocarcinoma, and benign glandular mimics.
abstract: The histopathologic distinction of cervical adenocarcinoma in situ (AIS) and invasive adenocarcinoma (AC) from some benign endocervical lesions can be challenging. The ProEx C antibody reagent targets nuclear proteins (minichromosome maintenance protein 2, MCM2 and topoisomerase II-alpha, TOP2A), which are over expressed during the aberrant S-phase induction of HPV infected and neoplastic cells. In this immunohistochemical study the utility of the ProEx C reagent in distinguishing AIS and AC from a variety of non-neoplastic glandular lesions was examined. ProEx C immunohistochemical staining was performed on sections from formalin-fixed, paraffin-embedded tissue of 65 cervical tissues including 48 non-neoplastic cervices (normal [n=10], microglandular hyperplasia [n=10], tubal metaplasia [n=11], cervical endometriosis [n=7], reactive endocervix [n=10]) and 17 cervices with glandular malignancy (AIS [n=12] and AC [n=5]). Both intensity and prevalence of immunoreactivity was scored. The median and distribution of scores for both prevalence and intensity was compared for AIS versus each of the 5 benign cervical lesions using a Mann-Whitney U test. The median and distribution of prevalence of immunohistochemical staining for AIS was different from all benign mimics, but the intensity of staining for AIS did overlap with some mimics as it was not significantly different from endometriosis, microglandular hyperplasia, and reactive endocervix. ProEx C reagent has potential as an adjunctive testing tool in the histopathologic diagnosis of both AIS and AC, particularly in difficult cases with small biopsies or foci of disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Dilinuer
authors.initials: D
authors.lastname: Aximu
authors.forename: Azar
authors.initials: A
authors.lastname: Azad
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Ni
authors.forename: Terence
authors.initials: T
authors.lastname: Colgan
authors.forename: Shabin
authors.initials: S
authors.lastname: Nanji
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods*; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010865:Pilot Projects; D000075223:Poly-ADP-Ribose Binding Proteins; D011933:Reagent Kits, Diagnostic; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011933:Reagent Kits, Diagnostic; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human