Pathare Swapnali M, Gerstung Moritz, Beerenwinkel Niko, Schäffer Alejandro A, Kannan Sadhana, Pai Prathamesh, Pathak K Alok, Borges Anita M, Mahimkar Manoj B
Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (TMC), Kharghar Node, Navi Mumbai-410210, India.
Oncol Lett. 2011 May;2(3):445-451. doi: 10.3892/ol.2011.271.
This study evaluated the clinicopathological and prognostic implications of genetic alterations characterizing oral squamous cell carcinoma(OSCC). Comparative genomic hybridization(CGH) was used to identify chromosomal alterations present in primary OSCCs obtained from 97 pateints. In this population, tobacco use was a significant risk factor for OSCC. By contrast, all 97 of our samples are negative for human papillomavirus (HPV) DNA integration, which is another known risk factor for OSCC in certain populations. Results of the Fisher's exact test followed by Benjamini-Hochberg correction for multiple testing, showed a correlation of 7p gain and 8p loss with node-positive OSCC (p≤0.04 for both genetic alterations) and association of 11q13 gain with high-grade OSCC (p≤0.05). Univariate Cox-proportional hazard models, also corrected for multiple testing, showed significant association of 11q13 gain and 18q loss with decreased survival (p≤0.05). These findings were supported by multivariate analysis which revealed that 11q13 gain and 18q loss together serve as a strong bivariate predictor of poor prognosis. In conclusion, our study has identified genetic alterations that correlate significantly with nodal status, grade, and poor survival status of OSCC. These potential biomarkers may aid the current TNM system for better prediction of clinical outcome.
本研究评估了口腔鳞状细胞癌(OSCC)基因改变的临床病理特征及预后意义。采用比较基因组杂交(CGH)技术鉴定了97例患者原发性OSCC中的染色体改变。在该人群中,吸烟是OSCC的一个重要危险因素。相比之下,我们所有97份样本的人乳头瘤病毒(HPV)DNA整合均为阴性,而在某些人群中,HPV是OSCC的另一个已知危险因素。经Benjamini-Hochberg多重检验校正后的Fisher精确检验结果显示,7p增益和8p缺失与淋巴结阳性OSCC相关(两种基因改变的p值均≤0.04),11q13增益与高级别OSCC相关(p≤0.05)。同样经多重检验校正的单变量Cox比例风险模型显示,11q13增益和18q缺失与生存率降低显著相关(p≤0.05)。多变量分析支持了这些发现,该分析显示11q13增益和18q缺失共同构成了预后不良的有力双变量预测指标。总之,我们的研究确定了与OSCC的淋巴结状态、分级及不良生存状态显著相关的基因改变。这些潜在的生物标志物可能有助于当前的TNM系统更好地预测临床结果。