Expression of Ki-67, tumor suppressor proteins, growth factor, and growth factor receptor in juvenile respiratory papillomatosis: Ki-67 and p53 as predictors of aggressive disease

The enhanced proliferation of epithelial cells is a typical feature of resp iratory papilloma. the mechanism or mechanisms leading to abnormal epitheli al proliferation remain unclear. Overexpression of growth factors and their receptors and inactivation of tumor-suppressor proteins are known to cause cell transformation and proliferation. The objectives of this study were t o evaluate the expression of these factors in juvenile respiratory papillom as with correlation to cellular proliferation activity, and to determine wh ether such expression is associated with the clinical course of the disease . The expression of transforming growth factor-alpha, epidermal growth fact or receptor, p53 protein, retinoblastoma proteins and Ki-67 was quantified by immunohistochemistry in paraffin-embedded biopsy specimens taken at the initial surgical excision from children in whom respiratory papillomatosis was diagnosed. Clinical information regarding the number of disease sites, tracheobronchial spread, malignant transformation, and frequency of recurre nces was reviewed. Thirty-five specimens were suitable for immunohistochemi cal evaluation. Ki-67 expression was significantly higher in patients with multiple sites of disease and frequent recurrences. High p53 expression was significantly associated with malignant transformation. We concluded that Ki-67 and p53 expression may be predictive of the clinical course in childr en with respiratory papillomatosis.