GNAS but Not Extended RAS Mutations Spectrum are Associated with a Better Prognosis in Intraductal Pancreatic Mucinous Neoplasms
GNAS but Not Extended RAS Mutations Spectrum are Associated with a Better Prognosis in Intraductal Pancreatic Mucinous Neoplasms
复制标题
DOI：
10.1245/s10434-019-07389-6
复制
发表时间：
2019-08-01
影响因子：
3.7
通讯作者：
Cros, Jerome
中科院分区：
文献类型：
--
作者：
Gaujoux, Sebastien;Parvanescu, Alina;Cros, Jerome
背景导管内乳头状黏液性肿瘤（intra-ductal papillary mucinous neoplasms，IPMNs）的治疗主要依据影像学特征和临床症状，仍具有挑战性。（KRAS、NRAS和HRAS）、BRAF和PIK 3CA突变状态，并将其与临床病理特征和患者生存率相关联。纳入了149例因IPMN接受胰腺切除术的连续性胰腺炎患者。在从福尔马林固定和石蜡包埋的肿瘤解剖后，使用Taqman（R）探针通过等位基因辨别来评估GNAS突变筛选，并通过SNaPshot分析来证实。RAS家族，BRAF，和PIK 3CA突变筛查进行了评估，高分辨率的熔体和桑格sequencing.ResultsGastric型和泌尿系型IPMNs是最常见的病变（52%和41%，分别）。肠型IPMN更常与高度异型增生相关（49%），是唯一与胶体型癌相关的IPMN。所有胰胆管IPMN均为侵袭性病变，位于主胰管。GNAS激活突变与肠道表型密切相关（p
BackgroundThe management of intraductal papillary mucinous neoplasms (IPMNs) is mainly based on imaging features and clinical symptoms, and remains challenging.ObjectiveThe aim of this study was to assess GNAS, RAS family (KRAS, NRAS and HRAS), BRAF, and PIK3CA mutation status in resected IPMNs and correlate it with clinicopathological characteristics and patient survival.MethodsOverall, 149 consecutive unselected patients who underwent pancreatectomy for IPMNs were included. After dissection from formalin-fixed and paraffin-embedded tumors, GNAS mutational screening was assessed by allelic discrimination using Taqman((R)) probes and confirmed by SNaPshot analysis. RAS family, BRAF, and PIK3CA mutational screening was assessed by high resolution melt and Sanger sequencing.ResultsGastric- and intestinal-type IPMNs were the most frequent lesions (52% and 41%, respectively). Intestinal-type IPMNs were more frequently associated high-grade dysplasia (49%) and were the only IPMNs associated with colloid-type carcinoma. All pancreatobiliary IPMNs were invasive lesions, located in the main pancreatic duct. GNAS-activating mutations were strongly associated with the intestinal phenotype (p