p16 Expression in Squamous Cell Carcinoma in Multiple Organ Sites
OA Asojo, H Al-Ghawi, K Wikenheiser-Brokamp, G Hill, F Lucas, QJ Zhai. University of Cincinnati, Cincinnati, OH; Greater Cincinnati Pathologists Inc., Cincinnati, OH
Background: p16 is a member the INK4 family of cell cycle regulatory proteins which keeps pRb, a tumor suppressor gene, in an unphosphorylated state thus maintaining its tumor suppressor activity. Following integration of the human papilloma (HPV) viral DNA into host genome, the viral E7 protein binds to and degrades pRb resulting in loss of tumor suppressor activity. This results in p16 upregulation by a positive feed back mechanism. HPV has been implicated in squamous cell carcinoma (SCC) in the anogenital and upper aerodigestive tracts. Its role in SCC of lung varies with location worldwide. Studies have implied the usefulness of p16 in discriminating between cervical SCC with lung metastases and primary lung SCC. We study the expression p16 in SCC in multiple sites to determine its usefulness as a marker in these sites.
Design: A total number of 56 cases of primary SCC were retrieved from our pathology archives and H&E stained slides were reviewed by 2 independent pathologists. The sites were lungs: 25 cases, anogenital area (cervix, vulva, anorectum): 8 cases, esophagus: 5 cases, skin: 7 cases and head/neck: 11 cases. Cases varied from well to moderately differentiated SCC. p16 immunohistochemical analysis was then performed on paraffin sections using an automated system (Ventana 1:200). Scoring was based on proportion of positive cells as follows: negative 0: <10%, weak 1+:10- 30%, moderate 2+: 50-75%, strong 3+: 75-100%. Nuclear or combined nuclear and cytoplasmic stains were considered specific.
Results: Of 25 cases of lung SCC, 40% were positive for p16. The proportion of positive cells was independent of degree of differentiation. All cases from the anogenital area were strongly positive, 40% of skin SCC were positive, 37.5% of head and neck SCC were positive and all cases of esophagus were negative (Table 1).
|P16 immunoreactivity score|
|SCC site||Number of cases||0||1+||2+||3+|
|Head & Neck||11||8||0||0||3|