Loss of p16(INK4a) expression correlates with decreased survival in pediatric osteosarcomas.
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.
Maitra
A
A
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. AMAITR@parknet.pmh.org
Roberts
H
H
Weinberg
A G
AG
Geradts
J
J
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001859:Bone Neoplasms / Q000378:metabolism* / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D019938:Cyclin D1 / Q000096:biosynthesis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D015536:Down-Regulation; D005260:Female; D016193:G1 Phase; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009336:Necrosis; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000378:metabolism* / Q000401:mortality*; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D013997:Time Factors
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein; D019938:Cyclin D1