Department of Pathology, National University Hospital, Singapore, 119228, Singapore.
Department of Medicine, National University Hospital, Singapore, 11928, Singapore.
Mod Pathol. 2020 Oct;33(10):2075-2086. doi: 10.1038/s41379-020-0520-5. Epub 2020 Apr 8.
Spasmolytic polypeptide-expressing metaplasia (SPEM) and pyloric gland adenoma (PGA) in the stomach are metaplastic and neoplastic lesions, respectively, in which gastric body glands are replaced by pyloric glands. The aim of this study was to evaluate the genomic profile of SPEM and compare it with intestinal-type gastric cancer (GC) and PGA. Thirteen gastrectomies showing PGA with or without dysplasia, GC and SPEM were retrospectively selected. MUC5AC, MUC6, gastrin, and TFF2 IHC were performed. Lesions were subjected to laser capture microdissection followed by DNA extraction. Forty-three DNA samples were extracted from PGA without cytological dysplasia, PGA with low-grade and high-grade dysplasia and pyloric gland adenocarcinoma, GC, SPEM, and adjacent normal tissue from the body of the stomach and were subjected to exome sequencing for 49 genes that are commonly dysregulated in GC. Sanger sequencing was performed for confirmation. Twenty nonsynonymous mutations were identified in SPEM, and none of these were frameshifts or indels. PGA with or without cytological dysplasia showed a significantly higher number of mutations compared with SPEM. As cytological dysplasia increased from no dysplasia to dysplasia in PGA, the percentage of frameshift mutations, indels, and missense variations increased. Further missense or frameshift mutations were observed in the KRAS, APC, TP53, and CTNNB1 genes in the PGA group. In GC, mutations were observed in the TP53 gene (p.Arg248Gln). Missense mutations in the MUC5AC, KRAS, BRAF, and EZH2 genes were common between SPEM and GC. SPEM showed fewer genomic variations than GC and PGA, and was genomically distinct from the pyloric epithelium in PGA. Stepwise progression of PGA from PGA without dysplasia to PGA with dysplasia/adenocarcinoma was associated an increase in mutations. SPEM appears to be more genomically similar to GC than PGA.
痉挛多肽表达化生（SPEM）和幽门腺腺瘤（PGA）分别是胃的化生和肿瘤性病变，其中胃体腺被幽门腺取代。本研究旨在评估 SPEM 的基因组特征，并将其与肠型胃癌（GC）和 PGA 进行比较。回顾性选择了 13 例伴有或不伴有异型增生的 PGA、GC 和 SPEM 胃切除术。进行了 MUC5AC、MUC6、胃泌素和 TFF2 IHC。对病变进行激光捕获显微切割，然后提取 DNA。从无细胞学异型增生的 PGA、低级别和高级别异型增生的 PGA 和幽门腺癌、GC、SPEM 以及胃体的相邻正常组织中提取了 43 个 DNA 样本，并对 49 个在 GC 中常被调控的基因进行外显子组测序。对 43 个样本进行了 Sanger 测序验证。在 SPEM 中发现了 20 个非同义突变，没有一个是移码或插入缺失。伴有或不伴有细胞学异型增生的 PGA 显示出明显更高数量的突变。随着 PGA 中细胞学异型增生从不典型增生发展到异型增生，移码突变、插入缺失和错义变异的比例增加。在 PGA 组中还观察到 KRAS、APC、TP53 和 CTNNB1 基因的进一步错义或移码突变。在 GC 中，观察到 TP53 基因（p.Arg248Gln）的突变。SPEM 和 GC 中常见 MUC5AC、KRAS、BRAF 和 EZH2 基因的错义突变。SPEM 的基因组变异比 GC 和 PGA 少，与 PGA 中的幽门上皮在基因组上明显不同。从无异型增生的 PGA 到伴有异型增生/腺癌的 PGA 的逐步进展与突变的增加有关。SPEM 似乎在基因组上与 GC 比与 PGA 更相似。
