Loss of p16INK4a expression correlates with decreased survival in Pediatric osteosarcomas

Anirban Maitra, Helen Roberts, Arthur G. Weinberg, Joseph Geradts

Research output: Contribution to journalArticle

Abstract

Abnormalities of the G1 cell-cycle checkpoint are commonly reported in cancers at various anatomic sites. pRB, p16INK4a 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, p16INK4a 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 p16INK4a expression. Cyclin D1 over-expression was not detected. There was an inverse correlation between loss of pRB and p16INK4a expression (p = 0.07). pRB and p16INK4a 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 p16INK4a expression significantly correlated with decreased survival in univariate analysis (p = 0.03), while loss of pRB expression did not affect survival. Immunohistochemical analysis of p16INK4a expression in pediatric osteosarcomas may be a useful adjunctive marker of prognosis.

Original languageEnglish (US)
Pages (from-to)34-38
Number of pages5
JournalInternational Journal of Cancer
Volume95
Issue number1
DOIs
StatePublished - Jan 20 2001
Externally publishedYes

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Keywords

  • Cyclin D1
  • Immunohistochemistry
  • Osteosarcoma
  • P16
  • Pediatric
  • PRB
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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