差异性不强的非乳头型小肠腺癌的分子景观及与克罗恩病的关联研究
Molecular Landscape and Association With Crohn Disease of Poorly Cohesive Carcinomas of the Nonampullary Small Bowel
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影响因子:1.9
分区:医学4区 / 病理学3区
发表日期:2023 Apr 04
作者:
Gianluca Tedaldi, Camilla Guerini, Davide Angeli, Daniela Furlan, Laura Libera, Marco Vincenzo Lenti, Federica Grillo, Matteo Fassan, Enrico Solcia, Fausto Sessa, Marco Paulli, Antonio Di Sabatino, Paola Ulivi, Alessandro Vanoli
DOI:
10.1093/ajcp/aqac161
摘要
差异性不强的癌（PCCs）是以主要呈弥散性生长模式、单细胞或索状间质浸润为特征的肿瘤。近年来，对非乳头型小肠PCCs（SB-PCCs）与常规型小肠腺癌在临床病理和预后方面的特征才刚刚被描述。然而，SB-PCCs的遗传特征尚未明确，我们旨在分析SB-PCCs的分子景观。采用Trusight Oncology 500进行下一代测序，分析15例非乳头型SB-PCCs的基因突变情况。结果显示，最常见的基因变异为TP53（53%）和RHOA（13%）突变，以及KRAS扩增（13%），未检测到KRAS、BRAF和PIK3CA突变。大多数SB-PCCs（80%）与克罗恩病相关，包括具有非SRC型组织学的RHOA突变肿瘤，以及表现出特殊的阑尾型、低级别杯状细胞腺癌（GCA）样成分。少数SB-PCCs表现出高微卫星不稳定性，或具有IDH1、ERBB2突变或FGFR2扩增（各一例），这些均是此类侵袭性癌症的已知或潜在治疗靶点。SB-PCCs可能携带RHOA突变，类似于胃癌弥漫型亚型或阑尾GCA，而KRAS和PIK3CA突变则不常见于此类癌症。
Abstract
Poorly cohesive carcinomas (PCCs) are neoplasms defined by a predominantly dyshesive growth pattern with single cell or cord-like stromal infiltration. The -distinctive clinicopathologic and prognostic features of small bowel PCCs (SB-PCCs) in comparison with conventional-type small intestinal adenocarcinomas have only recently been characterized. However, as SB-PCCs' genetic profile is still unknown, we aimed to analyze the molecular landscape of SB-PCCs.A next-generation sequencing analysis through Trusight Oncology 500 on a series of 15 nonampullary SB-PCCs was performed.The most frequently found gene alterations were TP53 (53%) and RHOA (13%) mutations and KRAS amplification (13%), whereas KRAS, BRAF, and PIK3CA mutations were not identified. Most SB-PCCs (80%) were associated with Crohn disease, including both RHOA-mutated SB-PCCs, which featured a non-SRC-type histology, and showed a peculiar appendiceal-type, low-grade goblet cell adenocarcinoma (GCA)-like component. Rarely, SB-PCCs showed high microsatellite instability, mutations in IDH1 and ERBB2 genes, or FGFR2 amplification (one case each), which are established or promising therapeutic targets in such aggressive cancers.SB-PCCs may harbor RHOA mutations, which are reminiscent of the diffuse subtype of gastric cancers or appendiceal GCAs, while KRAS and PIK3CA mutations, commonly involved in colorectal and small bowel adenocarcinomas, are not typical of such cancers.