Cyclin D1 Expression as a Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma
Juliette B Scantlebury, Jingqin Luo, Wade L Thorstad, Samir K El-Mofty, James S Lewis, Jr. Washington University Saint Louis, Saint Louis, MO
Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is a well-established entity with unique biology and improved prognosis. A new focus is to identify prognostic biomarkers specifically in this HPV positive cohort for use in determining appropriate therapy. Cyclin D1 expression has been suggested as being useful for this purpose.
Design: Immunohistochemistry was performed for cyclin D1 on a tissue microarray cohort of OSCC cases with known clinical follow up and p16 and HPV status (by RNA in situ hybridization/ISH). p16 positivity was defined as positive if ≥ 50% staining. Cyclin D1 staining was assessed visually for % positive cells by two study pathologists (JBS and JSL) and also by digital image analysis using Aperio's membrane algorithm, version 9. Cyclin D1 positivity was defined as ≥ 30% positive tumor cell staining.
Results: By visual analysis, 170 (84.2%) cases were cyclin D1 negative and 32 (15.8%) cases were positive. By image analysis, 167 (82.7%) cases were negative and 33 (16.3%) positive. The two methods of analysis were strongly correlated (Spearman's rank correlation coefficient =0.77). Of these cases, 150 (79.4%) were HPV RNA ISH positive and 39 (20.6%) negative. Negative cyclin D1 (by either method) correlated significantly (p < 0.05) with p16 and HPV positivity, with lower T-stage and higher N-stage, and also with non-smoking status. Positive cyclin D1 (be either method) correlated significantly with local and regional failure (p<0.05 for each) but not with distant metastases (visual p=0.33; digital p=0.12). In univariate analysis, negative cyclin D1 correlated strongly with better overall survival (visual p=1.56x10-5; digital p=4.58x10-7), but in multivariate it did not by either method (p>0.1 for each). In just the HPV RNA ISH positive patients, negative cyclin D1 also did not correlate significantly with overall survival (visual p=0.58; digital p=0.067).
Conclusions: Cyclin D1 expression (as < versus > 30%) correlates strongly with patient outcomes in OSCC. However, this correlation appears to be due to high correlation with HPV status and other prognostic variables so that cyclin D1 does not predict prognosis among just the HPV/p16 positive population.
Category: Head & Neck
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 201, Monday Morning