Mucinous lung adenocarcinoma, particularly referring to EGFR‐mutated mucinous adenocarcinoma
Mucinous lung adenocarcinoma, particularly referring to EGFR‐mutated mucinous adenocarcinoma
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DOI：
10.1111/pin.12879
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发表时间：
2019-12
影响因子：
2.2
通讯作者：
R. Wakejima;K. Inamura;H. Ninomiya;H. Nagano;M. Mun;S. Okumura;K. Okubo;Y. Ishikawa
中科院分区：
文献类型：
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作者：
R. Wakejima;K. Inamura;H. Ninomiya;H. Nagano;M. Mun;S. Okumura;K. Okubo;Y. Ishikawa
目前的2015年世界卫生组织（WHO）肺肿瘤分类没有充分分类粘液性肺腺癌。到目前为止，只有两种粘液腺癌的变种已被研究：浸润性粘液腺癌和胶样腺癌。此外，当它们产生粘蛋白时，侵袭性腺癌的常见类型尚未阐明，特别是表皮生长因子受体（EGFR）突变的粘液腺癌。在这项研究中，我们提取粘液腺癌的两个常见类型和两个变种。此外，我们还对它们的临床病理特征、突变模式以及甲状腺转录因子-1（TTF-1）、肝细胞核因子-4 α（HNF-4a）和粘蛋白的表达进行了化学和分子生物学检查，特别是针对EGFR突变的腺癌。在1159例手术切除的浸润性腺癌中，确定了189例粘液腺癌（16%）。其中EGFR突变、KRAS突变和ALK重排分别占20%、34%和9.5%。与EGFR突变的非粘液腺癌相比，EGFR突变的粘液腺癌没有女性优势，组织学分化程度较低，TTF-1表达较低，HNF-4a表达较高。此外，我们首次指出粘蛋白产生是EGFR突变腺癌的独立预后因素，并且MUC 5AC阴性和MUC 5 B阳性的粘蛋白染色模式是这些腺癌的特征。我们认为EGFR突变的粘液腺癌与EGFR突变的非粘液腺癌具有不同的致瘤途径。
The current 2015 World Health Organization (WHO) classification of lung tumors does not adequately categorize mucinous lung adenocarcinoma. Thus far, only two variants of mucinous adenocarcinoma have been studied: invasive mucinous adenocarcinoma and colloid adenocarcinoma. Moreover, common types of invasive adenocarcinoma when they produce mucin are yet to be elucidated, particularly epidermal growth factor receptor (EGFR)‐mutated mucinous adenocarcinoma. In this study, we extracted mucinous adenocarcinoma of both the common types and the two variants. Further, we immunohistochemically and molecular‐biologically examined their clinicopathological characteristics, mutation patterns, and expressions of thyroid transcription factor‐1 (TTF‐1), hepatocyte nuclear factor‐4 alpha (HNF‐4a) and mucins, particularly referring to EGFR‐mutated adenocarcinoma. Among 1159 surgically resected invasive adenocarcinomas, 189 mucinous adenocarcinomas (16%) were identified. Among these, 20%, 34% and 9.5% were EGFR mutated, KRAS mutated and ALK rearranged, respectively. Compared with EGFR‐mutated nonmucinous adenocarcinoma, EGFR‐mutated mucinous adenocarcinoma had no female predominance, lower grades of histological differentiation and lower TTF‐1 and higher HNF‐4a expressions. Moreover, for the first time, we indicated that mucin production was an independent prognostic factor for EGFR‐mutated adenocarcinomas and the mucin‐staining pattern of negative MUC5AC and positive MUC5B was characteristic in these adenocarcinomas. We suggest that EGFR‐mutated mucinous adenocarcinoma has a different tumorigenic pathway than nonmucinous EGFR‐mutated adenocarcinoma.