Higuchi Rumi, Nakagomi Takahiro, Goto Taichiro, Hirotsu Yosuke, Shikata Daichi, Yokoyama Yujiro, Otake Sotaro, Amemiya Kenji, Oyama Toshio, Mochizuki Hitoshi, Omata Masao
Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, Yamanashi 400-8506, Japan.
Department of Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
J Clin Med. 2020 Feb 20;9(2):573. doi: 10.3390/jcm9020573.
In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. In this study, we investigated the differences between clinical/histopathological and genomic diagnoses to determine whether they are primary or metastatic. 37 patients with multiple lung cancers were enrolled in this study. Tumor cells were selected from tissue samples using laser capture microdissection. DNA was extracted from those cells and subjected to targeted deep sequencing. In multicentric primary lung cancers, the driver mutation profile was mutually exclusive among the individual tumors, while it was consistent between metastasized tumors and the primary lesion. In 11 patients (29.7%), discrepancies were observed between genomic and clinical/histopathological diagnoses. For the lymph node metastatic lesions, the mutation profile was consistent with only one of the two primary lesions. In three of five cases with lymph node metastases, the lymph node metastatic route detected by genomic diagnosis differed from the clinical and/or pathological diagnoses. In conclusion, in patients with multiple primary lung cancers, cancer-specific mutations can serve as clonal markers, affording a more accurate understanding of the pathology of multiple lung cancers and their lymphatic metastases and thus improving both the treatment selection and outcome.
在多发性肺癌病例中，单个肿瘤可能代表原发性肺癌，也可能同时代表原发性和转移性肺癌。在本研究中，我们调查了临床/组织病理学诊断与基因组诊断之间的差异，以确定它们是原发性还是转移性的。37例多发性肺癌患者纳入本研究。使用激光捕获显微切割技术从组织样本中选取肿瘤细胞。从这些细胞中提取DNA并进行靶向深度测序。在多中心原发性肺癌中，驱动基因突变谱在各个肿瘤之间是相互排斥的，而在转移瘤和原发灶之间是一致的。在11例患者（29.7%）中，观察到基因组诊断与临床/组织病理学诊断之间存在差异。对于淋巴结转移灶，突变谱仅与两个原发性病灶之一一致。在五例有淋巴结转移的病例中，有三例通过基因组诊断检测到的淋巴结转移途径与临床和/或病理诊断不同。总之，在多发性原发性肺癌患者中，癌症特异性突变可作为克隆标记物，有助于更准确地了解多发性肺癌及其淋巴转移的病理学，从而改善治疗选择和治疗效果。
