Topoisomerase Alpha II, Retinoblastoma Gene Product, and p53: Potential Relationships With Aggressive Behavior and Malignant Transformation in Recurrent Respiratory Papillomatosis

Abstract

Recurrent respiratory papillomatosis (RRP) has a juvenile aggressive form and an adult more indolent form. Most cases of RRP are cytologically benign; however, some undergo malignant transformation. At present, there are no known markers that help identify patients at risk for aggressive disease. We investigated by immunohistochemistry expressions of topoisomerase alpha II, MIB-1, p53, p21, E-cadherin, retinoblastoma (RB) gene protein product, HER-2/neu, and steroid hormone receptors in a case of juvenile respiratory papillomatosis with malignant transformation to determine whether these markers are associated with malignant transformation. Histologic examination of the pulmonary lobectomy specimen revealed well-differentiated squamous carcinoma and invasive papillomatosis. Increased staining was found in areas of invasive papillomatosis for topoisomerase alpha II, p53, and MIB-1, with highest labeling indices in areas of squamous carcinoma. Staining intensity for RB gene protein product showed gradual decline from benign papilloma (3+) and invasive papillomatosis (2+) to squamous carcinoma (0-1+). Expression of p21 was similar in benign papilloma and invasive papillomatosis but showed reduction in squamous carcinoma. Expressions of E-cadherin, HER-2/neu, and steroid hormone receptors did not appear to correlate with biologic behavior. Increased topoisomerase alpha II and p53 expression along with reduced RB gene protein product and p21 expression may serve as markers of transformation to invasive papillomatosis and squamous carcinoma.