Russell Prudence A, Yu Yong, Young Richard J, Conron Matthew, Wainer Zoe, Alam Naveed, Solomon Benjamin, Wright Gavin M
Department of Anatomical Pathology, St Vincent's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
Research Division, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria, Australia.
Mod Pathol. 2014 Dec;27(12):1621-31. doi: 10.1038/modpathol.2014.71. Epub 2014 Apr 25.
The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification.
本研究旨在通过荧光原位杂交（FISH）检测肺癌患者队列中成纤维细胞生长因子受体1（FGFR1）扩增的患病率，并将结果与形态学、银原位杂交（SISH）及患者预后相关联。分别对406例和385例肺癌病例进行了FGFR1 FISH和SISH检测，并比较结果。FGFR1高水平扩增定义为FGFR1/8号染色体着丝粒≥2，或≥15个信号的肿瘤细胞百分比≥10%，或信号平均数/肿瘤细胞核≥6。FGFR1低水平扩增定义为≥5个信号的肿瘤细胞百分比≥50%。在检测的406例肿瘤中，有191例鳞状细胞癌、28例具有局灶性鳞状形态的癌、24例具有鳞状免疫表型的大细胞癌、115例腺癌、17例神经内分泌肿瘤以及31例无鳞状形态或免疫表型的癌。368例肿瘤的FGFR1 FISH检测结果可评估，其中50例检测到FGFR1扩增，包括48例具有鳞状形态或免疫表型的肿瘤（225例中的48例，21.3%），以及2例无鳞状或腺性形态及免疫表型的“无标记”肿瘤（143例中的2例，1.4%；P<0.0001）。347例肿瘤的FGFR1 SISH检测结果可评估。所有46例FGFR1 FISH检测扩增且有肿瘤组织可用于检测的肿瘤，SISH检测均显示扩增，而其他所有肿瘤均为阴性。在接受手术根治性治疗的具有任何鳞状形态或免疫表型的肿瘤患者中，FGFR1扩增状态与无病生存期（P=0.88，风险比[HR]=1.04，95%置信区间[CI]=0.67 - 1.60）或总生存期（P=0.97，HR=1.01，95% CI=0.65 - 1.58）之间无相关性。FGFR1扩增在具有任何鳞状形态或免疫表型的肿瘤中是一种常见异常，但也存在于“无标记”肿瘤中。FGFR1 SISH结果与FGFR1 FISH结果呈1:1相关性，表明SISH可能是检测FGFR1扩增的一种替代方法。未检测到患者预后与FGFR1扩增之间的关系。
