Clinicopathological and molecular correlations in traditional serrated adenoma
Clinicopathological and molecular correlations in traditional serrated adenoma
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DOI：
10.1007/s00535-020-01673-z
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发表时间：
2020-02-12
影响因子：
6.3
通讯作者：
Saito, Yutaka
中科院分区：
文献类型：
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作者：
Sekine, Shigeki;Yamashita, Satoshi;Saito, Yutaka
背景传统锯齿状腺瘤(TSA)是大肠锯齿状息肉中最少见的类型，具有相当大的形态和分子多样性。方法对128例TSA进行MAPK和WNT途径基因突变谱分析及其与临床病理特征的关系。结果测序分析发现BRAF V600E、BRAF Non-V600E、KRAS和NRAS突变分别为77个、3个、45个和1个。总共有124个病变(97%)有MAPK通路基因突变。WNT通路基因突变107个(84%)，其中RSPO融合/过表达、RNF43突变、ZNRF3突变、APC突变和CTNNB1突变分别为47、45、2、13和2个。10个病灶(8%)含有GNAS突变。改变的MAPK和WNT途径基因之间存在显著的相互依赖关系。RSPO融合/过表达与KRAS突变显著相关(31/47，66%)，而大多数RNF43突变与BRAF V600E突变共存(40/45，89%)。组织学上，广泛的裂隙状锯齿状在BRAF V600E突变(71%)和RNF43突变(87%)的皮损中更常见。在RSPO融合/过度表达(58%)和GNAS突变(100%)的病变中，显著的异位隐窝形成更常见。结论我们的观察表明，TSA大多同时存在WNT和MAPK基因改变的各种组合。遗传和形态特征之间的关联表明，TSA的组织学多样性反映了潜在的分子异质性。
Background Traditional serrated adenoma (TSA) is the least common type of colorectal serrated polyp, which exhibits considerable morphological and molecular diversity. Methods We examined the spectra of alterations in MAPK and WNT pathway genes and their relationship with clinicopathological features in 128 TSAs. Results Sequencing analyses identified BRAF V600E, BRAF non-V600E, KRAS, and NRAS mutations in 77, 3, 45, and 1 lesion, respectively. Collectively, 124 lesions (97%) had mutations in MAPK pathway genes. Alterations in WNT pathway genes were identified in 107 lesions (84%), including RSPO fusions/overexpression, RNF43 mutations, ZNRF3 mutations, APC mutations, and CTNNB1 mutations in 47, 45, 2, 13, and 2 lesions, respectively. Ten lesions (8%) harbored GNAS mutations. There was significant interdependence between the altered MAPK and WNT pathway genes. RSPO fusions/overexpression was significantly associated with KRAS mutations (31/47, 66%), whereas most RNF43 mutations coexisted with the BRAF V600E mutation (40/45, 89%). Histologically, extensive slit-like serration was more common in lesions with the BRAF V600E mutation (71%) and those with RNF43 mutations (87%). Prominent ectopic crypt formation was more prevalent in lesions with RSPO fusions/overexpression (58%) and those with GNAS mutations (100%). Conclusions Our observations indicate that TSAs mostly harbor various combinations of concurrent WNT and MAPK gene alterations. The associations between genetic and morphological features suggest that the histological diversity of TSA reflects the underlying molecular heterogeneity.