Loss of p16(ink4a) expression correlates with decreased survival in pediatric osteosarcomas

Abnormalities of the G(1) cell-cycle checkpoint are commonly reported in ca ncers at various anatomic sites. pRB, p16(INK4a) and cyclin D1 are critical G(1)-checkpoint proteins responsible for maintaining the balance of cellul ar proliferation. We examined a series of 38 pediatric osteosarcomas for ab normal expression of pRB, p16(INK4a) and cyclin DI by immunohistochemical a nalysis of archival biopsy specimens. Overall, 17/38 (45%) osteosarcomas sh owed evidence of G(1)-checkpoint abrogation, including 11/38 (29%) with los s of pRB expression and 6/38 (16%) with loss of p16(INK4a) expression. Cycl in DI over-expression was not detected. There was an inverse correlation be tween loss of pRB and p16(INK4a) expression (p = 0.07), pRB and p16(INK4a) abnormalities were independent of site of disease, presence of metastasis a t diagnosis and percentage of tumor necrosis in the resection specimen. Cli nical follow-up was available on all patients (median 31.6 months, range 5. 9-116 months). Absence of p16(INK4a) expression significantly correlated wi th decreased survival in univariate analysis (p = 0.03), while loss of pRB expression did not affect survival. Immunohistochemical analysis of p16(INK 4a) expression in pediatric osteosarcomas may be a useful adjunctive marker of prognosis. (C) 2001 Wiley-Liss, Inc.