靶向DNA测序揭示胰腺导管内乳头状黏液性肿瘤（IPMN）切除术后胰腺残余局部进展模式。
Targeted DNA Sequencing Reveals Patterns of Local Progression in the Pancreatic Remnant Following Resection of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas.
作者信息
Pea Antonio, Yu Jun, Rezaee Neda, Luchini Claudio, He Jin, Dal Molin Marco, Griffin James F, Fedor Helen, Fesharakizadeh Shahriar, Salvia Roberto, Weiss Matthew J, Bassi Claudio, Cameron John L, Zheng Lei, Scarpa Aldo, Hruban Ralph H, Lennon Anne Marie, Goggins Michael, Wolfgang Christopher L, Wood Laura D
机构信息
*Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland †Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy ‡Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland §Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy ¶Departments of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland ||Departments of Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland **ARC-Net applied research on cancer center, University and Hospital Trust of Verona, Verona, Italy.
出版信息
Ann Surg. 2017 Jul;266(1):133-141. doi: 10.1097/SLA.0000000000001817.
OBJECTIVE
The aim of this study was to characterize patterns of local progression following resection for pancreatic intraductal papillary mucinous neoplasms (IPMN) using targeted next-generation sequencing (NGS).
BACKGROUND
Progression of neoplastic disease in the remnant pancreas following resection of IPMN may include development of a new IPMN or ductal adenocarcinoma (PDAC). However, it is not clear whether this progression represents recurrence of the same neoplasm or an independent second neoplasm.
METHODS
Targeted-NGS on genes commonly mutated in IPMN and PDAC was performed on tumors from (1) 13 patients who developed disease progression in the remnant pancreas following resection of IPMN; and (2) 10 patients who underwent a resection for PDAC and had a concomitant IPMN. Mutations in the tumors were compared in order to determine the relationship between neoplasms. In parallel, clinical and pathological characteristics of 260 patients who underwent resection of noninvasive IPMN were reviewed to identify risk factors associated with local progression.
RESULTS
We identified 3 mechanisms underlying local progression in the remnant pancreas: (1) residual microscopic disease at the resection margin, (2) intraparenchymal spread of neoplastic cells, leading to an anatomically separate but genetically related recurrence, and (3) multifocal disease with genetically distinct lesions. Analysis of the 260 patients with noninvasive IPMNs showed that family history of pancreatic cancer (P = 0.027) and high-grade dysplasia (HGD) (P = 0.003) were independent risk factors for the development of an IPMN with HGD or an invasive carcinoma in the remnant pancreas.
CONCLUSIONS
Using NGS, we identify distinct mechanisms for development of metachronous or synchronous neoplasms in patients with IPMN. Patients with a primary IPMN with HGD or with positive family history are at an increased risk to develop subsequent high-risk neoplasms in the remnant pancreas.
目的
本研究旨在利用靶向二代测序（NGS）来描述胰腺导管内乳头状黏液性肿瘤（IPMN）切除术后局部进展的模式。
背景
IPMN切除术后残余胰腺内肿瘤性疾病的进展可能包括新发IPMN或导管腺癌（PDAC）的发生。然而，这种进展是代表同一肿瘤的复发还是独立的第二种肿瘤尚不清楚。
方法
对以下两组患者的肿瘤进行IPMN和PDAC中常见突变基因的靶向NGS检测：（1）13例IPMN切除术后残余胰腺发生疾病进展的患者；（2）10例行PDAC切除术且伴有IPMN的患者。比较肿瘤中的突变以确定肿瘤之间的关系。同时，回顾了260例行非侵袭性IPMN切除术患者的临床和病理特征，以确定与局部进展相关的危险因素。
结果
我们确定了残余胰腺局部进展的3种机制：（1）手术切缘残留微小病灶；（2）肿瘤细胞的实质内播散，导致解剖学上分离但遗传学相关的复发；（3）具有基因不同病变的多灶性疾病。对260例非侵袭性IPMN患者的分析表明，胰腺癌家族史（P = 0.027）和高级别异型增生（HGD）（P = 0.003）是残余胰腺发生HGD或侵袭性癌的IPMN的独立危险因素。
结论
通过NGS，我们确定了IPMN患者异时性或同时性肿瘤发生的不同机制。原发性IPMN伴有HGD或家族史阳性的患者，残余胰腺发生后续高危肿瘤的风险增加。
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