P53 Expression in Oropharyngeal Squamous Cell Carcinoma Is Increased in HPV Positive Smokers
Madalina Tuluc, Voichita Bar-Ad, Zoe Wang, Joseph Curry. Jefferson University Hospital, Philadelphia, PA
Background: Patients with HPV-positive oropharyngeal carcinoma (OSCC) have a better prognosis than patients with HPV-negative OSCC. Differences in expression of cell cycle and survival proteins and p53 gene mutations have been identified between HPV-positive and HPV-negative OSCC. HPV E6 protein inactivates p53,therefore HPV positive OSCC have low expression of p53. In contrast, in chemical/toxin induced OSCC p53 is overexpressed and it is associated with poor prognosis and resistance to treatment.
This study evaluates p53 expression in HPV positive and HPV negative OSCC patients with and without smoking history.
Design: 101 cases of OSCC, 65 p16 positive and 36 p16 negative patients were retrospectively collected. The two groups have been divided in nonsmokers, smokers and patients with remote smoking history (who quit smoking at least 3 years prior to diagnosis).
Immunohistochemistry stains for p16 and p53 were performed on all cases. The staining pattern for p53 has been defined as low expression (less than 20% of the nuclei positive) or high expression (more than 20% nuclear staining).
Results: There were significant differences in p53 staining pattern between p16 positive and p16 negative patients. P16 negative smokers (current and remote smokers) had the highest percentage of p53 overexpression (38 and 40%, respectively).
The highest percentage of p53 overexpression in the p16 positive patients was in the smokers group, 15% of cases.
In p16 positive nonsmokers only 4% of patients showed high p53 staining. p53 levels in nonsmokers, p16 positive and p16 negative was low (under 10%).
Conclusions: In the p16 negative group, patients with current and remote smoking history showed the highest p53 expression. This is concordant with the literature data that suggests that p53 is overexpressed in non HPV related head and neck SCC.
Our study brings strong evidence that in HPV positive patients with OSCC that are current smokers there is an increase in p53 expression, at a level that is intermediary between p16 positive nonsmokers and p16 negative smokers. We hypothesize that smoking partially reverses the effect of E6 HPV protein on p53 inactivation. The small percentage of HPV positive nonsmokers with high p53 expression suggests that in HPV OSCC other pathways, independent of HPV, may be involved in p53 inactivation, hypothesis that may carry therapeutic and prognostic implications.
Category: Head & Neck
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 170, Wednesday Morning