Maitra A, Roberts H, Weinberg A G, Geradts J
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Int J Cancer. 2001 Jan 20;95(1):34-8. doi: 10.1002/1097-0215(20010120)95:1<34::aid-ijc1006>3.0.co;2-v.
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.
G1期细胞周期检查点异常在各种解剖部位的癌症中普遍存在。pRB、p16(INK4a)和细胞周期蛋白D1是维持细胞增殖平衡的关键G1期检查点蛋白。我们通过对存档活检标本进行免疫组织化学分析，检测了38例儿童骨肉瘤中pRB、p16(INK4a)和细胞周期蛋白D1的异常表达。总体而言，38例骨肉瘤中有17例(45%)显示有G1期检查点废除的证据，包括38例中有11例(29%)pRB表达缺失，38例中有6例(16%)p16(INK4a)表达缺失。未检测到细胞周期蛋白D1过表达。pRB缺失与p16(INK4a)表达之间呈负相关(p = 0.07)。pRB和p16(INK4a)异常与疾病部位、诊断时是否存在转移以及切除标本中肿瘤坏死百分比无关。所有患者均有临床随访(中位时间31.6个月，范围5.9 - 116个月)。在单因素分析中，p16(INK4a)表达缺失与生存率降低显著相关(p = 0.03)，而pRB表达缺失不影响生存率。儿童骨肉瘤中p16(INK4a)表达的免疫组织化学分析可能是一种有用的预后辅助标志物。
