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Loss of p16 INK4a expression correlates with decreased survival in pediatric osteosarcomas
Author(s) -
Maitra Anirban,
Roberts Helen,
Weinberg Arthur G.,
Geradts Joseph
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010120)95:1<34::aid-ijc1006>3.0.co;2-v
Subject(s) - immunohistochemistry , cyclin d1 , medicine , univariate analysis , cancer research , biopsy , pathology , cell cycle , oncology , cancer , multivariate analysis
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 1 ‐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. © 2001 Wiley‐Liss, Inc.