P16 Immunoreactivity in CIN1 Predicts Malignant Progression to High-Grade Dysplasia
Michael S Landau, Yun Zhao, Bin Yang. Cleveland Clinic Foundation, Cleveland, OH; Peking University People's Hospital, Peking, China
Background: P16 immunohistochemistry is widely used to facilitate accurate diagnosis of high grade cervical dysplasia (CIN2-3). It has also been noted that a subgroup of CIN1 lesions shows focal p16 immunoreactivity. However, the clinical significance of focal p16 expression in CIN1 is largely unknown. To investigate whether focal p16 expression in CIN1 confers risk of progression to high-grade dysplasia, we compared long-term clinical outcomes of women with p16-negative CIN1 and p16-positive CIN1. We systematically studied follow-up data including HPV testing, cytology, colposcopy-guided biopsy, LEEP, and conization in 243 patients initially diagnosed with CIN1.
Design: A cohort of 243 consecutive patients diagnosed with CIN1 on biopsy was retrieved from our hospital archive and reviewed. P16 immunostaining (MTM antibody, Ventana, Arizona) was performed on all cases. Results of p16 staining patterns were recorded as negative, focal, or diffuse. Follow-up information, including HPV testing, cytology, biopsy, LEEP, and conization diagnoses, were reviewed and tabulated for up to 36 months.
Results: A total of 243 women with CIN1 lesions were included in the study. Based on p16 immunoreactivity, CIN1 was divided into two groups: p16-negative CIN1 (123, 50.6%) and p16-positive CIN1 120 (49.4%). Cervical biopsy, LEEP, and/or conization were performed on 116 patients. The remaining 127 patients who were clinically considered to be low risk were followed subsequently with HPV testing and/or cervical cytology. HPV infection persisting for at least 12 months was seen in 66 (27%) patients, of whom 29 (43.9%) had p16-negative CIN1 and 37 (56.1%) had p16-positive CIN1. CIN1 persisting for at least 12 months was seen in 27 patients, including 13 with p16-negative CIN1 and 14 with p16-positive CIN1. Twenty-six (10.7%) patients progressed to CIN2-3. Among those, 25 (96.2%) had p16-positive CIN1 and one (3.8%) had p16-negative CIN1 (P<0.0001). Patients with p16-positive CIN1 progressed to CIN2-3 at a significantly higher rate than those with p16-negative CIN1 (21% vs. 1%, p<0.0001).
Conclusions: Our study shows that patients with p16-positive CIN1 are significantly more likely to progress to high-grade dysplasia than those with p16-negative CIN1. Also, of the patients with CIN1 who progressed to high-grade dysplasia, the overwhelming majority (96%) had p16-positive lesions on biopsy. These data suggest that focal p16 staining in CIN1 may represent an early event of malignant transformation.
Category: Gynecologic & Obstetrics
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 179, Monday Morning