Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Lung Cancer. 2014 May;84(2):121-6. doi: 10.1016/j.lungcan.2014.02.007. Epub 2014 Feb 19.
To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas.
Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations.
There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients.
This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.
全面调查融合阳性肺腺癌的临床病理、组织学和细胞学特征。
对 1139 例中国肺腺癌患者的切除肿瘤样本同时进行实时荧光定量逆转录聚合酶链反应（qRT-PCR）和逆转录聚合酶链反应（RT-PCR）筛选 ALK、ROS1 和 RET 融合，通过荧光原位杂交验证阳性结果。评估融合阳性肺腺癌的临床病理特征、主要组织学亚型和细胞学形态，并与 EGFR、KRAS、HER2 或 BRAF 突变的肿瘤进行比较。
发现 58 例（5.1%）ALK 融合、11 例（1.0%）ROS1 融合和 15 例（1.3%）RET 融合。ROS1 融合阳性肿瘤的直径明显大于 ROS1 融合阴性肿瘤（P = 0.007），而所有 15 例携带 RET 融合的肿瘤直径均≤3cm（P = 0.001）。这三个融合基因在以实体为主的腺癌中更为常见。与融合阴性肺腺癌相比，携带融合基因的肿瘤具有更高的细胞外粘蛋白（P < 0.001）、筛状模式（P < 0.001）、印戒细胞（P < 0.001）和肝细胞样细胞学（P < 0.001）的发生率。在无复发生存率（P = 0.147）和总生存率（P = 0.444）方面，融合阳性和融合阴性患者之间没有观察到显著差异。
本研究表明融合阳性肺腺癌具有可识别的共同和融合模式特异性临床病理、组织学和细胞学特征，为融合基因筛查提供了依据。
