Expression of p16 in CIN2-3 Lesions with Negative HPV Status
Gloria Zhang, Bin Yang, Fadi W Abdul-Karim. Cleveland Clinic, Cleveland, OH
Background: Knowledge of the HPV status often influences pathologists' decision in rendering diagnosis of cervical dysplasia. A subset of CIN2-3 lesions is found in those women with negative HPV test. P16 as a surrogate marker for HPV integation has been applied to facilitate accurate diagnosis of high grade dysplasia. To determine if there is any difference of p16 immunostaining pattern between HPV-positive and HPV-negative CIN2-3 lesions, we compared p16 immunohistochemistry in 76 cases of high grade cervical dysplasia with either HPV-negative or HPV-positive status.
Design: Thirty-six women with histopathologic diagnoses of CIN2-3 and negative HPV status were identified from our hospital archives. All women had at least one HPV testing on cervical smear collections using HCII (Qiagen) within 6 months of initial biopsy. Forty cases of CIN2-3 lesions with confirmed positive HPV status were included as control. Immunohistochemical staining was performed using p16 antibody from Vantana. P16 immunostaining patterns were evaluated as negative, focal, and diffuse pattern. Patients' clinicopathology information were reviewed and correlated with p16 immunostain.
Results: Of 76 patients diagnosed with CIN2-3, 40 patients had positive HPV and 36 patients had negative HPV status. P16 immunoreactivity was seen in 75 (98.7%) of all CIN2-3 cases, including 40 (100%) cases of HPV-positive cases and 35 (97.2%) of HPV-negative cases. Diffuse staining pattern was seen in all 40 cases of HPV-positive CIN2-3 lesions. Among cases with negative HPV status, p16 immunostaining revealed 28 (77.8%) cases with diffuse staining pattern, 7 (19.4%) cases with focal staining pattern and 1 (2.8%) case with negative p16 staining. On retrospective review, 4/7 cases with focal pattern would have been re-classified as CIN1 or condyloma and all these 4 cases had subsequent negative LEEP. The remaining 3/7 cases with focal pattern had focal CIN2 in a background of CIN1. CIN2-3 lesions were found in all subsequent LEEP specimen. The only case with negative p16 staining showed immature squamous metaplasia with a negative LEEP on follow up.
Conclusions: Expression of p16 was seen in all cases with CIN2-3 lesions, regardless of HPV status. Diffuse p16 staining pattern is the hallmark for high grade dysplasia. Our data suggest that p16 immunostain is a more sensitive tool in facilitating accurate diagnosis of CIN2-3. In our experience, when dealing with borderline and challenging cases, the pathologists are advised to be careful in rendering the diagnosis of high grade in the presence of negative or focal p16 staining pattern.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 224, Tuesday Afternoon