Fluorescence in situ hybridization for detecting genomic alterations of cyclin D1 and p16 in oral squamous cell carcinomas
Fluorescence in situ hybridization for detecting genomic alterations of cyclin D1 and p16 in oral squamous cell carcinomas
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DOI：
10.1002/cncr.23030
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发表时间：
2007-11-15
期刊：
影响因子：
6.2
通讯作者：
Amagasa, Teruo
中科院分区：
文献类型：
--
作者：
Uzawa, Narikazu;Sonoda, Ltaru;Amagasa, Teruo
背景。在口腔鳞状细胞癌（SCCs）中检测到细胞周期蛋白D1 （CCND1）和p16的改变，提示这些基因的异常可能在口腔鳞状细胞癌的发生或进展中起重要作用，并可作为独立的预后指标。利用一种简单、灵敏的方法检测CCND1和p16的畸变，对于开发有效的口腔癌治疗方法具有重要价值。本研究的目的是确定通过荧光原位杂交（FISH）检测口腔SCCs中CCND1数值畸变和p16缺失是否对临床结果有任何影响。使用CCND1和p16基因组DNA探针，对57例原代口腔sccs通过细针穿刺（FNA）获得的标本进行FISH检测。57例口腔SCCs患者中有28例（49%）观察到CCND1数值畸变，并与无病生存期（P = 0.0004）和总生存期（P = 0.0179）降低显著相关。相反，57例患者中有22例（39%）检测到p16缺失。p16缺失患者的无病生存率和总生存率低于无p16缺失患者，但差异未达到统计学意义（P = 0.0516, P = 0.1878）。存在CCND1数值畸变的p16缺失可显著降低无病生存期（P - 0.0002）和总生存期（P = 0.0153）。尽管CCND1数值畸变是口腔SCCs患者侵袭性肿瘤、复发和预后不良的良好预测指标，但与单独分析任何一种改变相比，作者能够通过FNA活检样本上的FISH评估p16缺失和CCND1遗传状态，更有效地识别出早期疾病复发和预后不良的患者亚组。
BACKGROUND. Cyclin D1 (CCND1) and p16 alterations have been detected in oral squamous cell carcinomas (SCCs), suggesting that abnormalities of these genes may play an important role in the genesis or progression of oral SCCs and serve as independent prognostic indicators. The detection of CCND1 and p16 aberrations using a simple and sensitive method would be valuable for the development of effective treatment modalities for oral cancer. The objective of the current study was to determine whether CCND1 numerical aberrations and p16 deletions in oral SCCs detected by fluorescence in situ hybridization (FISH) have any impact on clinical outcome.METHODS. Using genomic DNA probes for CCND1 and p16, FISH was performed on specimens that were obtained by fine-needle aspiration (FNA) from 57 primary oral SCCs.RESULTS. The CCND1 numerical aberration was observed in 28 of 57 patients (49%) with oral SCCs and was associated significantly with reduced disease-free survival (P = .0004) and overall survival (P = .0179). Conversely, p16 deletion was detected in 22 of 57 patients (39%). The disease-free and overall survival rates for patients with p16 deletion were lower than those among patients without the p16 deletion, although the difference just failed to reach statistical significance (P = .0516 and P = .1878, respectively). The p16 deletion in the presence of the CCND1 numerical aberration conferred significantly worse disease-free survival (P - .0002) and overall survival (P = .0153).CONCLUSIONS. Although the CCND1 numerical aberration was a good predictor of aggressive tumors, recurrence, and poor prognosis in patients with oral SCCs, the authors were able to identify subgroups of patients that had early disease recurrence and a poor prognosis more efficiently by assessment of p16 deletion in addition to CCND1 genetic status using FISH on FNA biopsy samples compared with the analysis of either alteration alone.