Loss of p16(INK4a) expression correlates with decreased survival in pediatric osteosarcomas.

Journal Article (Journal Article)

Abnormalities of the G1 cell-cycle checkpoint are commonly reported in cancers at various anatomic sites. pRB, p16(INK4a) and cyclin D1 are critical G1-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 G1-checkpoint 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.

Full Text

Duke Authors

Cited Authors

  • Maitra, A; Roberts, H; Weinberg, AG; Geradts, J

Published Date

  • January 20, 2001

Published In

Volume / Issue

  • 95 / 1

Start / End Page

  • 34 - 38

PubMed ID

  • 11241308

International Standard Serial Number (ISSN)

  • 0020-7136

Digital Object Identifier (DOI)

  • 10.1002/1097-0215(20010120)95:1<34::aid-ijc1006>3.0.co;2-v


  • eng

Conference Location

  • United States