[1046] Evaluation of the Combined Utility of p16 and ProEx C Immunohistochemistry in Distinguishing Endocervical Glandular Neoplasia from Its Benign Glandular Mimics

N Banet, C Livasy. Univ of North Carolina, Chapel Hill, NC

Background: Cervical adenocarcinoma accounts for 15-25% of all cervical cancers. Identification of endocervical glandular neoplasia (EGN) in cervical specimens may be difficult due to small sample size and/or the presence of benign glandular mimics. Proteins p16, topoisomerase II alpha, and MMP2 have been shown to be upregulated in HPV-associated neoplasia. The aim of this study was to evaluate the combined utility of p16 and ProEx C in distinguishing EGN from its benign glandular mimics.
Design: Patients were selected retrospectively including those with endocervical adenocarcinoma in situ (AIS), usual-type invasive endocervical adenocarcinoma and several benign glandular mimics. Representative sections from each case were selected for immunohistochemical (IHC) studies for p16 and ProEx C. The IHC slides were reviewed by two pathologists and scored for intensity (0-3) and percent staining.
Results:

ProEx C and p16 results

	0%	1-25%	26-49%	50-75%	>75%
p16
Normal endocervix (n=8)	2	6	0	0	0
Tubal metaplasia (n=10)	2	2	0	5	1
Endometriosis (n=8)	0	3	2	3	0
Inflammatory atypia (n=8)	5	3	0	0	0
Microglandular hyperplasia (n=8)	8	0	0	0	0
AIS (n= 11)	0	0	0	0	11
Invasive adenocarcinoma (n= 9)	1	0	0	0	8
ProEx C
Normal endocervix (n= 8)	1	7	0	0	0
Tubal metaplasia (n=10)	1	7	1	1	0
Endometriosis (n=8)	2	3	3	0	0
Inflammatory atypia (n=8)	1	7	0	0	0
Microglandular hyperplasia (n=8)	2	5	0	1	0
AIS (n=11)	0	0	0	0	11
Invasive adenocarcinoma (n=9)	0	0	0	1	8

Both p16 and ProExC showed diffuse staining in essentially 100% of neoplastic cells in all 11 AIS lesions and in 8 of 9 invasive endocervical adenocarcinomas. Both biomarkers correlated strongly with EGN (p<0.001). There were a total of 9 benign glandular mimics showing ≥ 50% staining for p16, such that interpretation of result could be difficult in a small biopsy specimen. In 8 of these cases the corresponding ProEx C showed <50% staining suggesting a potential improvement in specificity from 79% to 97% in this study if ProEx C added.
Conclusions: Only diffuse staining for p16 or ProEx C should be considered as strongly supportive of the diagnosis of endocervical glandular neoplasia. In small samples where percent staining may be difficult to assess, a combined p16/ProEx C panel is likely to improve specificity as compared to p16 alone.
Category: Gynecologic & Obstetrics

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 147, Monday Morning