Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation.
Associations between mutations and histologic patterns of mucin in lung adenocarcinoma: invasive mucinous pattern and extracellular mucin are associated with KRAS mutation.
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DOI：
10.1097/pas.0000000000000246
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发表时间：
2014-08
期刊：
影响因子：
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通讯作者：
Travis WD
中科院分区：
文献类型：
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作者：
Kadota K;Yeh YC;D'Angelo SP;Moreira AL;Kuk D;Sima CS;Riely GJ;Arcila ME;Kris MG;Rusch VW;Adusumilli PS;Travis WD
多份报告表明，表皮生长因子受体（EGFR）突变与类上皮型肺腺癌相关，KRAS突变与浸润性粘液腺癌相关。我们试图研究EGFR和KRAS突变与特定形态学特征（如主要组织学亚型和粘液特征）之间的相关性。收集了864例接受EGFR和KRAS突变分子检测的切除肺腺癌患者的临床数据。根据IASLC/ATS/ERS肺腺癌分类进行组织学分型，注意印戒细胞特征和细胞外粘蛋白。使用基于聚合酶链反应的大小测定法检测EGFR突变，使用桑格测序法检测KRAS突变，使用免疫组织化学法检测ALK表达。浸润性粘液腺癌与KRAS突变有关（P<0.001）。在KRAS突变的浸润性粘液腺癌中，纯粘液型比粘液/非粘液混合型更常见（P=0.002）。与非粘液性肿瘤相比，侵袭性粘液腺癌与KRAS转换突变（G→A）相关，但与颠换突变（G→T或G→C）无关（P=0.009）。与非瘦素占优势的肿瘤相比，瘦素占优势的肿瘤组与EGFR突变相关（P=0.011）。细胞外粘蛋白与KRAS突变相关（P<0.001），而印戒细胞特征与EGFR或KRAS突变无关（P=0.517）。ALK表达与印戒细胞特征相关（P=0.001），但与细胞外粘蛋白无关（P=0.089）。我们的研究表明，肺腺癌中粘蛋白的组织学模式-包括浸润性粘液腺癌和细胞外粘蛋白-与KRAS突变相关。
Multiple reports indicate that epidermal growth factor receptor (EGFR) mutations are associated with lepidic-pattern lung adenocarcinoma, and that KRAS mutations are associated with invasive mucinous adenocarcinoma. We sought to investigate the association between EGFR and KRAS mutations and specific morphologic characteristics, such as predominant histologic subtype and mucinous features. Clinical data for 864 patients with resected lung adenocarcinoma that underwent molecular testing for EGFR and KRAS mutations were collected. Histologic subtyping was performed according to the IASLC/ATS/ERS lung adenocarcinoma classification, with attention given to signet-ring cell feature and extracellular mucin. EGFR mutations were detected using a polymerase chain reaction–based sizing assay, KRAS mutations were detected using Sanger sequencing, and ALK expression was detected using immunohistochemistry. Invasive mucinous adenocarcinoma was associated with KRAS mutation (P<0.001). Among invasive mucinous adenocarcinomas with KRAS mutation, a pure mucinous pattern was more common than a mixed mucinous/nonmucinous pattern (P=0.002). Invasive mucinous adenocarcinoma was associated with KRAS transition mutations (G→A) but not transversion mutations (G→T or G→C) compared to non-mucinous tumors (P=0.009). The lepidic-predominant group was associated with EGFR mutation compared to nonlepidic-predominant tumors (P=0.011). Extracellular mucin was associated with KRAS mutation (P<0.001), whereas signet-ring cell feature was not associated with EGFR or KRAS mutation (P=0.517). ALK expression was associated with signet-ring cell feature (P=0.001) but not with extracellular mucin (P=0.089). Our study shows that histologic patterns of mucin in lung adenocarcinoma - including invasive mucinous adenocarcinoma and extracellular mucin - are associated with KRAS mutation.