Utilization of p16 and ProEx C Staining in Differential Diagnosis of Atypical Cells in Liquid-Based Pap Tests during Menstruation.
Yimin Ge, Dina R Mody, Debora A Smith, Rose C Anton. The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX
Background: Though the Pap test is an effective screening tool for cervical carcinoma, some diagnostic pitfalls do exist. This is especially true when evaluating hyperchromatic crowded groups (HCGs) in Pap tests from women during menstruation due to similar morphological appearances between endometrial clusters and precancerous or malignant HCGs. Previous studies demonstrated that p16 and ProEx C are often expressed in cervical precancerous or malignant lesions. We studied the results of p16 and ProEx C on cell blocks from Pap tests with atypical cells during menstruation to attempt to differentiate endometrial cells from cervical dysplastic lesions.
Design: Immunohistochemical stains for p16 and ProEx C were performed on 21 cell blocks prepared from residual liquid-based cervical material with endometrial contamination. The cases include 10 benign (NILM), 4 low grade squamous intraepithelial lesion (LSIL), 5 high grade squamous intraepithelial lesion (HSIL), 1 endometrial adenocarcinoma, and 1 metastatic breast carcinoma. Endometrial biopsies from non-neoplastic cycling endometrium were studied as a control.
Results: Strong, diffuse and full thickness staining pattern for p16 and ProEx C was observed in all cases of HSIL. The cases of LSIL were negative for ProExC with weak patchy basal-predominant staining for p16. In contrast, all cases of NILM were negative for both p16 and ProEx C stains. The endometrial cells in the background were either negative or had focal patchy staining. Weak staining was focally seen in 1 case of endometrial adenocarcinoma and 1 case of metastatic breast carcinoma. Endometrial biopsies at various functional phases showed patchy staining pattern for both p16 and ProEx C.
Conclusions: ProEx C and p16 are strongly and diffusely positive in HSIL. ProEx C is negative in LSIL with p16 only focally positive in the basal layer. The stains should be interpreted with caution because patchy/mosaic staining pattern can be seen in benign endometrial tissue, especially in proliferative phase or with tubal metaplasia. In addition, ProEx C staining is usually cleaner than p16 staining. Therefore, combination of both p16 and ProEx C immunostains and being aware of various staining patterns are critical in accurate interpretation of results. The authors believe the proposed method will be significantly helpful in differential diagnosis of HCGs in menstrual Pap specimens.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 101, Tuesday Morning