Fang Lianghua, Chen Hui, Tang Zhenya, Kalhor Neda, Liu Ching-Hua, Yao Hui, Hu Shimin, Lin Pei, Zhao Jin, Luthra Raja, Singh Rajesh R, Routbort Mark J, Hong David, Medeiros L Jeffrey, Lu Xinyan
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China.
Oncotarget. 2018 Feb 7;9(16):12959-12970. doi: 10.18632/oncotarget.24430. eCollection 2018 Feb 27.
To investigate the prognostic impact of copy number (-CN) in patients with non-small cell lung cancer (NSCLC), we retrospectively reviewed clinical and pathologic data of NSCLC patients whose tumors were assessed for -CN using fluorescence hybridization (FISH). We correlated -CN status with patient overall survival (OS) and optimized -FISH reporting criteria. The study group included 384 patients with NSCLC of which 88% were adenocarcinoma and 55.7% of patients had distant metastases. There were 170 patients with stages I-III and 214 patients with stage IV disease. Based on the -CN and /CEP7 ratio the patients were classified into 3 categories: -amplification (amp): /CEP7 ≥ 2 or -CN ≥ 5; -CN-gain (cng): -CN ≥ 4 to < 5; and -negative (neg): -CN < 4. amp was associated with high fatality (=.036) and stage IV tumors (=.038). In patients with stages I-III NSCLC, patients in the amp category had the shortest OS (=.015) and more often developed distant metastases within 1 year (=.004). In patients with stage IV tumors, amp did not further impact the OS. Patients in the cng category had the longest OS (=.053). Multivariate analysis confirmed amp to be an independent high-risk factor (HR 3.26; =.026) and predicted earlier progression to distant metastasis (HR 4.86; =.001). In conclusion, we suggest that the -FISH criteria presented optimizes risk stratification by defining 3 categories of NSCLC patients. amp is an independent risk factor predicting early distant metastasis and patients with cng could represent a lower-risk group.
为了研究拷贝数（-CN）对非小细胞肺癌（NSCLC）患者预后的影响，我们回顾性分析了NSCLC患者的临床和病理数据，这些患者的肿瘤通过荧光原位杂交（FISH）检测了-CN。我们将-CN状态与患者总生存期（OS）相关联，并优化了FISH报告标准。研究组包括384例NSCLC患者，其中88%为腺癌，55.7%的患者有远处转移。有170例I-III期患者和214例IV期患者。根据-CN和/CEP7比值，患者被分为3类：-扩增（amp）：/CEP7≥2或-CN≥5；-CN增加（cng）：-CN≥4至<5；以及-阴性（neg）：-CN<4。amp与高死亡率（P =.036）和IV期肿瘤（P =.038）相关。在I-III期NSCLC患者中，amp组患者的OS最短（P =.015），且在1年内更常发生远处转移（P =.004）。在IV期肿瘤患者中，amp并未进一步影响OS。cng组患者的OS最长（P =.053）。多因素分析证实amp是一个独立的高危因素（HR 3.26；P =.026），并预测更早进展为远处转移（HR 4.86；P =.001）。总之，我们建议所提出的FISH标准通过定义3类NSCLC患者优化了风险分层。amp是预测早期远处转移的独立危险因素，而cng组患者可能代表低风险组。
