S-PHASE FRACTION AS A PREDICTOR OF PROGNOSIS IN JUVENILE RESPIRATORY PAPILLOMATOSIS

Objective: To determine whether DNA ploidy and the S-phase fraction ar e predictive of the clinical course in children with recurrent respira tory papillomatosis. Design: Masked compression of DNA analysis findin gs to the clinical course of the disease. Setting: Tertiary referral c enter. Patients: All pediatric patients treated for recurrent respirat ory papillomatosis at our institution between 1989 and 1995 who had ad equate follow-up and whose primary biopsy specimen was available for e xamination. Fifty-five patients met these criteria. Methods: Informati on was collected from the case notes on the patient's age at presentat ion, sex, sites of disease, duration of active disease, and frequency of operative interventions. Flow cytometric analysis was performed on the archival paraffin-embedded primary biopsy specimen obtained at the initial surgical excision, providing DNA content and percentages of S -phase cells. The investigators who performed the DNA analysis were ma sked to the clinical course. Results: The age of the patients at prese ntation ranged from 3 months to 16 years. Thirty patients had involvem ent in more than I anatomical site. The disease in 10 patients had spr ead to the distal tracheobronchial tree. The patients underwent a tota l of 1124 procedures, with a frequency range of 7 to 27 per year. All cell populations studied were diploid. The percentage of S-phase cells was significantly higher in the primary biopsy specimen from patients with disease characterized by more frequent recurrences, multiple sit es, and distal extension (P<.05). In multiple regression analysis, the S-phase fraction was found to be an independent and powerful prognost ic factor for aggressive disease. Conclusions: The S-phase fraction ma y be predictive of the clinical course in patients with juvenile respi ratory papillomatosis. Prospective studies are needed to assess the di agnostic and clinical value of our primary results and to determine wh ether DNA analysis can assist in identifying patients at increased ris k for an aggressive clinical course.