Loss of p16INK4a expression correlates with decreased survival in pediatric osteosarcomas

✍ Scribed by Anirban Maitra; Helen Roberts; Arthur G. Weinberg; Joseph Geradts

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: French
• Weight: 348 KB
• Volume: 95
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/1097-0215(20010120)95:1<34::aid-ijc1006>3.0.co;2-v

✦ Synopsis

Abnormalities of the G

1 cell-cycle checkpoint are commonly reported in cancers at various anatomic sites. pRB, p16 INK4a and cyclin D1 are critical G 1 -checkpoint proteins responsible for maintaining the balance of cellular proliferation. We examined a series of 38 pediatric osteosarcomas for abnormal expression of pRB, p16 INK4a and cyclin D1 by immunohistochemical analysis of archival biopsy specimens. Overall, 17/38 (45%) osteosarcomas showed evidence of G 1checkpoint abrogation, including 11/38 (29%) with loss of pRB expression and 6/38 (16%) with loss of p16 INK4a expression. Cyclin D1 over-expression was not detected. There was an inverse correlation between loss of pRB and p16 INK4a expression (p ‫؍‬ 0.07). pRB and p16 INK4a abnormalities were independent of site of disease, presence of metastasis at diagnosis and percentage of tumor necrosis in the resection specimen. Clinical follow-up was available on all patients (median 31.6 months, range 5.9 -116 months). Absence of p16 INK4a expression significantly correlated with decreased survival in univariate analysis (p ‫؍‬ 0.03), while loss of pRB expression did not affect survival. Immunohistochemical analysis of p16 INK4a expression in pediatric osteosarcomas may be a useful adjunctive marker of prognosis.