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A Pilot Evaluation of a Novel Immunohistochemical Assay for Topoisomerase II-α and Minichromosome Maintenance Protein 2 Expression (ProEx C) in Cervical Adenocarcinoma In Situ, Adenocarcinoma, and Benign Glandular Mimics

Aximu, Dilinuer M.D.; Azad, Azar Ph.D.; Ni, Ruoyu B.Med.; Colgan, Terence M.D.; Nanji, Shabin M.B.Bchir.

International Journal of Gynecological Pathology: March 2009 - Volume 28 - Issue 2 - p 114-119
doi: 10.1097/PGP.0b013e3181895573

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-α, 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.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

Dr Dilinuer Aximu was supported by China Scholarship Council (CSC) of Ministry of Education of the P.R. China and Mount Sinai Hospital. TriPath (BD Diagnostics) provided the ProEx C.

Address correspondence and reprint requests to Shabin Nanji, MBBchir, Pathology and Laboratory Medicine, Room 6-500-7, Mount Sinai Hospital, Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Toronto, Ontario, Canada, M5G 1×5. E-mail:

©2009International Society of Gynecological Pathologists