Biomarker (ProEx C, p16INK4A, and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics

Abstract

Topoisomerase IIa and minichromosome maintenance protein 2 are proteins associated with aberrant S-phase induction. The current study evaluated the performance of these biomarkers (ProExt C; TriPath Oncology, Burlington, NC) compared with p16INK4A and MiB-1 in distinguishing high-grade squamous intraepithelial lesions (HSILs) from HSIL mimics. We collected archival cervical biopsy, cone, and curettage specimens from 96 cases in which the differential diagnosis of HSIL vs reactive epithelial changes was considered. Hematoxylinand eosin-stained slides were reviewed independently by three pathologists and scored for the presence or absence of SIL. Immunostains for ProEx C, p16, and MiB-1 were available for 95, 96, and 59 samples, respectively, and classified blinded to histological interpretation. Strong nuclear and cytoplasmic staining for p16 and staining for MiB-1 and ProEx C that extended beyond the lower one-third of the epithelium were scored as positive. v 2 -tests and receiver operating characteristic analysis were conducted to statistically compare biomarker immunostaining performance against majority histological interpretation of SIL. Agreement between pathologists was also assessed by the j-statistic. Inter-observer agreement ranged from fair to moderate (j ¼ 0.37-0.57). All three biomarkers correlated strongly with the majority diagnosis of SIL (Po0.001). Positive staining for ProEx C, p16, and MiB-1 was observed in 87% (N ¼ 52/60), 84% (N ¼ 51/61), and 94% (34/36), respectively, of SIL and negative in 71% (N ¼ 25/35), 63% (N ¼ 22/35), and 52% (N ¼ 12/23), respectively, of majority diagnoses of NoSIL. The combination of p16/ProEx C predicted more SIL (92%, N ¼ 33/36) and NoSIL (61%, N ¼ 14/23) than p16 plus MiB-1 (94%, N ¼ 34/36 and 43%, N ¼ 10/23), although this difference was not statistically significant. ProEx C appears to provide an equivalent level of sensitivity and a higher level of specificity for HSIL alone or in conjunction with p16. Its principal value may be in providing a lower false positive rate for NoSIL relative to MiB-1.

Biomarker expression in cervical intraepithelial neoplasia: potential progression predictive factors for low-grade lesions

“…Another important issue is the expression of these markers in CIN mimics. Immature squamous metaplasia was not examined in this study, but Pinto et al presented two cases of diagnostically problematic immature metaplasia, both of which were negative on ProEx C staining [15]. Larger studies with many cases of CIN mimics seem necessary to conclude this issue.…”

Evaluation of cervical cone biopsies for coexpression of p16INK4a and Ki‐67 in epithelial cells

“…23 This may depend on an equivocal morphological grade of the lesion, and atrophy, reactive changes and some squamous metaplasia are mimics of high-grade intraepithelial neoplasia and might cause misinterpretations. 24,25 …”

Evaluation Of P16, P27, Cycline D1, Bcl-2 Expressions In Uterine Cervical Intraepithelial Neoplasia and Skuamous Cell Carcinoma

“…Ancak ayırıcı tanıda ortaya çıkan güçlükler, lezyonun gerileyip, gerilemeyeceği, invaziv karsinoma mı dönüşeceğinin öngörülememe-si ve patologlarda gözlemciler arası uyumsuzluklar, araştırmacıları objektif kriterler kullanmaya yönelt-miş, lezyonların ayrımında pratikte yararlı olabilecek immün belirteçlerin araştırılmasına gereksinim duyulmuştur (12,13) .…”