Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinoma.
Clinicopathological and genetic differences between low-grade and high-grade colorectal mucinous adenocarcinoma.
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低级别和高级别结直肠粘液腺癌之间的临床病理学和遗传差异。
作者：
Yoshioka Y;Togashi Y;Chikugo T;Kogita A;Terashima M;Mizukami T;Hayashi H;Sakai K;de Velasco MA;Tomida S;Fujita Y;Tokoro T;Ito A;Okuno K;Nishio K
虽然传统上认为结直肠粘液腺癌（MCs）表现出高级别分化，但根据腺体外观，它们可以根据分化分为两组：低级别粘液腺癌（low - MC）和高级别粘液腺癌（high - MC）。方法本研究纳入2000年至2012年间接受手术切除的结直肠癌（CRC）患者。在MC病例中，通过下一代测序研究低- MC和高- MC的临床病理和遗传差异。结果共分析了1373例结直肠癌患者。40例（2.9%）患者有MC， 13例患者有高MC。MC患者的无病生存期（DFS）和总生存期（OS）明显短于非黏液癌患者。当比较低- MC患者和高- MC患者时，高- MC患者的DFS和OS期明显短于低- MC患者。多变量分析显示，高MC与较短的DFS和较短的OS显著相关，但低MC与此无关。基因组分析显示，低MC比高MC有更多的突变，Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）突变和腺瘤性大肠息肉病突变在低MC中特别常见。相反，SMAD家族成员4 （SMAD4）突变在高MC中经常被发现。结论高MC是CRC的独立预后因素（但低MC不是），并且在遗传学上不同于其他CRC，包括低MC。临床病理差异和遗传差异表明，低- MC和高- MC应在临床环境中加以区分。©2015美国癌症协会。
BACKGROUNDAlthough colorectal mucinous adenocarcinomas (MCs) are conventionally regarded as exhibiting high‐grade differentiation, they can be divided by differentiation into 2 groups according to the glandular appearance: low‐grade mucinous adenocarcinoma (low‐MC) and high‐grade mucinous adenocarcinoma (high‐MC).METHODSPatients with colorectal cancer (CRC) who underwent surgical resection between 2000 and 2012 were enrolled in this study. Among the cases with MC, the clinicopathological and genetic differences between low‐MC and high‐MC were investigated with next‐generation sequencing.RESULTSA total of 1373 patients with CRC were analyzed. Forty patients (2.9%) had MC, and 13 patients had high‐MC. Patients with MC had significantly shorter disease‐free survival (DFS) and overall survival (OS) periods than those with nonmucinous carcinoma. When low‐MC patients and high‐MC patients were compared, those with high‐MC had significantly shorter DFS and OS periods than those with low‐MC. Multivariate analyses revealed that high‐MC was significantly associated with both shorter DFS and shorter OS, but low‐MC was not. A genome analysis revealed that low‐MC had a considerably larger number of mutations than high‐MC, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and adenomatous polyposis coli mutations were particularly frequently found in low‐MC. In contrast, SMAD family member 4 (SMAD4) mutations were frequently found in high‐MC.CONCLUSIONSHigh‐MC is an independent prognostic factor in CRC (but low‐MC is not), and it is genetically different from other CRCs, including low‐MC. Both the clinicopathological differences and the genetic differences suggest that low‐MC and high‐MC should be distinguished in clinical settings.Cancer2015;121:4359–68. ©2015 American Cancer Society.