Expression of p21 in Oropharyngeal Squamous Cell Carcinoma Is Associated with HPV Status but Is Not an Independent Prognostic Marker
Meredith E Pittman, Samir El-Mofty, Wade Thorstad, James S Lewis. Washington University in St Louis, St Louis, MO
Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing over the past three decades. High risk human papillomavirus (HPV) is associated with OPSCC, and patients with HPV have a better prognosis. This finding has prompted research into other potential prognostic biomarkers, one of which is expression of the tumor suppressor protein p21.
Design: Immunohistochemistry was performed for p21 on a tissue microarray cohort of OPSCC cases with known clinical follow-up and HPV status (by RNA in situ hybridization [ISH]). Expression of p21 was assessed visually by a study pathologist (MEP) and also by digital image analysis using Aperio's membrane algorithm, version 9. Expression of p21 was frequent and extensive and was therefore dichotomized as >= versus < 75% staining.
Results: There were 214 patients identified, the majority of whom were men (90%) of Caucasian race (88%) who smoked (71%). The mean age at diagnosis was 55. HPV RNA was detected in 81% of the tumors tested. All tumors had some p21 expression, with a mean of 60% by visual analysis and 52% by digital analysis. By visual analysis, 40 patients (19%) had extensive p21 staining (75% or more); by digital analysis, 12 patients (6%). Pearson's correlation between visual and digital analysis was strong (r=0.7). Diffuse p21 staining was more frequent in HPV negative patients (p=<0.001), more frequent in patients with T3 and T4 tumors (p=0.04), and less frequent in those undergoing surgical treatment (p=0.03). Kaplan-Meier survival analysis showed that diffuse p21 expression, lack of HPV, high T stage, and non-surgical treatment were each individually associated with decreased overall survival (p<0.05). Diffuse p21 expression was not associated with disease free or disease specific survival in univariate analyses. In multivariate Cox regression analysis for overall survival, high T stage (HR 2.6; 95%CI 1.5, 4.7) and lack of HPV (HR 2.9; 95% CI 1.5, 5.4) remained significant predictors of patient demise, but p21 expression and treatment type were no longer statistically significant.
Conclusions: Although diffuse p21 expression may suggest more aggressive tumors in patients with OPSCC, it is not an effective independent prognostic biomarker when controlling for well-established risk factors such as T-stage and HPV status.
Category: Head & Neck
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 194, Monday Morning