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人喉鳞状细胞癌中细胞周期蛋白D1基因扩增:预后意义及临床影响

Cyclin D1 gene amplification in human laryngeal squamous cell carcinomas: prognostic significance and clinical implications.

作者信息

Bellacosa A, Almadori G, Cavallo S, Cadoni G, Galli J, Ferrandina G, Scambia G, Neri G

机构信息

Institutes of Medical Genetics, Otorhinolaryngology, and Obstetrics and Gynecology, Catholic University Medical School, Largo F. Vito 1, 00168 Rome, Italy.

出版信息

Clin Cancer Res. 1996 Jan;2(1):175-80.

PMID:9816104
Abstract

The cyclin D1 (CCND1) gene is amplified, rearranged, and overexpressed frequently in human cancer, including squamous cell carcinoma. The gene dosage of CCND1 was examined in 51 primary laryngeal squamous cell carcinomas, and amplification of the gene was found in 9 (17.6%) cases. CCND1 amplification did not correlate with age, tumor localization and extension, cervical lymph node involvement, histopathological grading, and epidermal growth factor receptor levels. In a univariate analysis, CCND1 amplification, tumor extension, lymph node involvement, poor histological differentiation, and high epidermal growth factor receptor levels were correlated significantly with shorter overall survival. In a median follow-up period of 29 months, the overall survival rate was 71.4% for patients affected with tumors displaying a normal CCND1 dosage and only 25.0% for patients affected with tumors carrying amplified CCND1 (P = 0.0288). In a multivariate analysis, only CCND1 and tumor extension retained statistically significant prognostic values (P = 0.037 and 0.041, respectively). This is the first report in which CCND1 amplification is identified as a significant independent prognostic factor in laryngeal carcinoma. Evaluation of CCND1 amplification could be applicable to the clinical management of laryngeal cancer, allowing identification of patients with poor prognoses.

摘要

细胞周期蛋白D1(CCND1)基因在包括鳞状细胞癌在内的人类癌症中经常发生扩增、重排和过表达。在51例原发性喉鳞状细胞癌中检测了CCND1的基因剂量,发现9例(17.6%)存在该基因的扩增。CCND1扩增与年龄、肿瘤定位和范围、颈部淋巴结受累情况、组织病理学分级以及表皮生长因子受体水平均无相关性。单因素分析显示,CCND1扩增、肿瘤范围、淋巴结受累、组织学分化差以及表皮生长因子受体水平高与总生存期较短显著相关。在中位随访期29个月时,CCND1剂量正常的肿瘤患者总生存率为71.4%,而携带CCND1扩增的肿瘤患者总生存率仅为25.0%(P = 0.0288)。多因素分析显示,只有CCND1和肿瘤范围保留了具有统计学意义的预后价值(分别为P = 0.037和0.041)。这是首次报道将CCND1扩增确定为喉癌的一个重要独立预后因素。对CCND1扩增的评估可应用于喉癌的临床管理,有助于识别预后不良的患者。

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