A combination of molecular markers and clinical features improve the classification of pancreatic cysts.
A combination of molecular markers and clinical features improve the classification of pancreatic cysts.
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DOI：
10.1053/j.gastro.2015.07.041
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发表时间：
2015-11
期刊：
影响因子：
29.4
通讯作者：
Lennon AM
中科院分区：
文献类型：
--
作者：
Springer S;Wang Y;Dal Molin M;Masica DL;Jiao Y;Kinde I;Blackford A;Raman SP;Wolfgang CL;Tomita T;Niknafs N;Douville C;Ptak J;Dobbyn L;Allen PJ;Klimstra DS;Schattner MA;Schmidt CM;Yip-Schneider M;Cummings OW;Brand RE;Zeh HJ;Singhi AD;Scarpa A;Salvia R;Malleo G;Zamboni G;Falconi M;Jang JY;Kim SW;Kwon W;Hong SM;Song KB;Kim SC;Swan N;Murphy J;Geoghegan J;Brugge W;Fernandez-Del Castillo C;Mino-Kenudson M;Schulick R;Edil BH;Adsay V;Paulino J;van Hooft J;Yachida S;Nara S;Hiraoka N;Yamao K;Hijioka S;van der Merwe S;Goggins M;Canto MI;Ahuja N;Hirose K;Makary M;Weiss MJ;Cameron J;Pittman M;Eshleman JR;Diaz LA Jr;Papadopoulos N;Kinzler KW;Karchin R;Hruban RH;Vogelstein B;Lennon AM
胰腺囊肿的治疗对患者及其医生都构成了挑战。我们研究了结合分子标志物和临床信息是否可以改善胰腺囊肿的分类和患者的治疗。我们对130例切除的胰腺囊性肿瘤患者进行了一项多中心回顾性研究（12例浆液性囊腺瘤、10例实性假乳头状肿瘤、12例粘液性囊性肿瘤和96例导管内乳头状粘液性肿瘤）。分析囊液以鉴定已知在胰腺囊肿中突变的基因（BRAF、CDKN 2A、CTNNB 1、GNAS、KRAS、NRAS、PIK 3CA、RNF 43、SMAD 4、TP 53和VHL）中的微小突变;鉴定CDKN 2A、RNF 43、SMAD 4、TP 53和VHL肿瘤抑制基因座处的杂合性缺失;并鉴定非整倍性。使用用于实施和解释大规模并行测序数据采集的专门技术进行分析。使用算法来选择可以分类囊肿类型和等级的标记物。将分子标记物的准确性与临床标记物的准确性以及分子标记物和临床标记物的组合进行比较。我们确定了分子标记物和临床特征，以90%-100%的敏感性和92%-98%的特异性分类囊肿类型。分子标记物小组正确地识别了74名不需要手术的患者中的67名，因此可以将不必要的手术数量减少91%。我们确定了一组分子标志物和临床特征，这些标志物和临床特征有望对胰腺囊性肿瘤进行准确分类，并确定需要手术的囊肿。
The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid-pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53 and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers were compared with that of clinical markers, and a combination of molecular and clinical markers. We identified molecular markers and clinical features that classified cyst type with 90%–100% sensitivity and 92%–98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery, and could therefore reduce the number of unnecessary operations by 91%. We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.