Correlation of p16 and pRb expression with HPV detection in Bowen's disease

Background: Bowen's disease is a form of cutaneous squamous cell carcinoma which may be caused by ultraviolet radiation, human papilloma virus (HPV) infection, or other causes. Although p16 over-expression is a surrogate marker of HPV E7-mediated catabolism of pRb in premalignant and malignant lesions of the cervical mucosa, the correlation of p16 and pRb expression with HPV detection in Bowen's disease has not been well characterized. Methods: A retrospective study on formalin-fixed tissues was performed. Immunohistochemistry for p16 and pRb was performed on 32 cases. DNA was successfully extracted from 20 cases, and polymerase chain reaction was performed to amplify a highly conserved region of the HPV L1 open reading frame. Results: Twenty-eight of 32 (88%) cases showed strong diffuse staining for p16 but were negative for pRb; two of 32 cases (6%) were negative for p16 but were diffusely positive for pRb; one case was strongly positive for both p16 and pRb, and one case was negative for both p16 and pRb. Three of 20 cases (15%) contained HPV DNA. All three of these cases showed strong p16 expression and lack of pRb staining. Conclusions: Most cases of Bowen's disease strongly express p16 but not pRb. In contrast to HPV-associated lesions of the cervical mucosa, p16 overexpression in cutaneous Bowen's disease appears to be unrelated to HPV status. The p16 overexpression in Bowen's disease may reflect disruption of the G1/S checkpoint, resulting in unregulated cell cycle progression.