Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma
Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma
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DOI：
10.1111/pin.13316
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发表时间：
2023-03
影响因子：
2.2
通讯作者：
M. Higashiyama;N. Motoi;M. Yotsukura;Y. Yoshida;K. Nakagawa;S. Yagishita;Masayuki Shirasawa;T. Yoshida;K. Shiraishi;T. Kohno;Y. Ohe;Shun-ichi Watanabe
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文献类型：
--
作者：
M. Higashiyama;N. Motoi;M. Yotsukura;Y. Yoshida;K. Nakagawa;S. Yagishita;Masayuki Shirasawa;T. Yoshida;K. Shiraishi;T. Kohno;Y. Ohe;Shun-ichi Watanabe
纤毛结节乳头状瘤/细支气管腺瘤(CMPT/BA)是新近发现的一种肺部良性肿瘤。目前尚不清楚CMPT/BA是否与特定类型的肺癌(LC)有关。我们研究了原发性LC和CMPT/BA(LCCM)并存的临床病理特征和基因特征。我们从切除的0-III期原发性LC(n=1945)中鉴定出8例LCCM(0.4%)。LCCM队列以男性为主(n=8)，老年人(中位年龄72岁)，大多数是吸烟者(n=6)。除了腺癌(n=8)，我们还发现了两种鳞状细胞癌和一种小细胞癌--在某些情况下，是多发性癌症。靶序列/外显子全序列(WES)显示CMPT/BA和LC之间没有共同的突变。一个例外情况是侵袭性粘液腺癌携带HRAS突变(I46N，c.137T>；A)，但它很可能是基于变异等位基因频率(VAF)的单核苷酸多态。其他致病基因突变包括EGFR(Indel，n=2)、BRAF(V600E)(n=1)、KRAS(n=2)、GNAS(n=1)和TP53(n=2)。BRAF(V600E)是CMPT/BA中最常见的突变(60%)。相比之下，LC在DIVER基因突变方面没有显示出特定的趋势。总之，我们的研究揭示了CMPT/BA和LC并存病例中基因突变谱的差异，提示CMPT/BA在LC中主要是独立的克隆性肿瘤发生。
Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a recently introduced benign lung tumor. It remains unclear whether CMPT/BA is associated with a specific type of lung cancer (LC). We studied the clinicopathological characteristics and genetic profiles of the coexisting primary LC and CMPT/BA (LCCM) cases. We identified eight LCCM (0.4%) from the resected Stage 0–III primary LC (n = 1945). The LCCM cohort was male‐dominant (n = 8), elderly (median 72 years old), and most were smokers (n = 6). In addition to the adenocarcinoma (n = 8), we detected two squamous cell carcinomas and one small cell carcinoma—in some cases, multiple cancer. The target sequence/whole exome sequence (WES) revealed no shared mutations between CMPT/BA and LC. One exceptional case was invasive mucinous adenocarcinoma harboring an HRAS mutation (I46N, c.137T>A), but it was likely to be a single nucleotide polymorphism based on variant allele frequency (VAF). Other driver mutations in LC included EGFR (InDel, n = 2), BRAF(V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2). BRAF(V600E) was the most frequent mutation in CMPT/BA (60%). In contrast, LC showed no specific trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation profiles of CMPT/BA and LC in coexisting cases, suggesting mostly independent clonal tumorigenesis of CMPT/BA from LC.