A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

被引：359

作者：

Springer, Simeon ^{[1
,2
,3
]}

Wang, Yuxuan ^{[1
,2
,3
]}

Dal Molin, Marco ^{[3
,4
]}

Masica, David L. ^{[3
,5
,6
,7
]}

Jiao, Yuchen ^{[1
,2
,3
]}

Kinde, Isaac ^{[1
,2
,3
]}

Blackford, Amanda ^{[8
]}

Raman, Siva P. ^{[9
]}

Wolfgang, Christopher L. ^{[3
,10
,11
]}

Tomita, Tyler ^{[5
,6
,7
]}

Niknafs, Noushin ^{[5
,6
,7
]}

Douville, Christopher ^{[5
,6
,7
]}

Ptak, Janine ^{[1
,2
,3
]}

Dobbyn, Lisa ^{[1
,2
,3
]}

Allen, Peter J. ^{[12
]}

Klimstra, David S. ^{[13
]}

Schattner, Mark A. ^{[14
]}

Schmidt, C. Max ^{[15
]}

Yip-Schneider, Michele ^{[16
]}

Cummings, Oscar W. ^{[16
]}

Brand, Randall E. ^{[17
]}

Zeh, Herbert J. ^{[18
]}

Singhi, Aatur D. ^{[19
]}

Scarpa, Aldo ^{[20
,21
]}

Salvia, Roberto ^{[22
]}

Malleo, Giuseppe ^{[22
]}

Zamboni, Giuseppe ^{[21
,23
]}

Falconi, Massimo ^{[24
]}

Jang, Jin-Young ^{[25
,26
]}

Kim, Sun-Whe ^{[25
,26
]}

Kwon, Wooil ^{[25
,26
]}

Hong, Seung-Mo ^{[27
]}

Song, Ki-Byung ^{[28
]}

Kim, Song Cheol ^{[28
]}

Swan, Niall ^{[29
]}

Murphy, Jean ^{[29
]}

Geoghegan, Justin ^{[30
]}

Brugge, William ^{[31
]}

Fernandez-Del Castillo, Carlos ^{[32
]}

Mino-Kenudson, Mari ^{[33
]}

Schulick, Richard ^{[34
]}

Edil, Barish H. ^{[34
]}

Adsay, Volkan ^{[35
]}

Paulino, Jorge ^{[36
]}

van Hooft, Jeanin ^{[37
]}

Yachida, Shinichi ^{[38
,39
]}

Nara, Satoshi ^{[38
,39
]}

Hiraoka, Nobuyoshi ^{[38
,39
]}

Yamao, Kenji

Hijioka, Susuma ^{[40
]}

机构：

[1] Johns Hopkins Univ, Ludwig Ctr, Baltimore, MD USA

[2] Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA

[3] Johns Hopkins Univ, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA

[4] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA

[5] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA

[6] Johns Hopkins Univ, Johns Hopkins Med Inst, Baltimore, MD USA

[7] Johns Hopkins Univ, Inst Computat Med, Baltimore, MD USA

[8] Johns Hopkins Univ, Dept Biostat & Bioinformat, Baltimore, MD USA

[9] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA

[10] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA

[11] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA

[12] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA

[13] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA

[14] Mem Sloan Kettering Canc Ctr, Dept Gastroenterol, New York, NY 10021 USA

[15] Indiana Univ, Dept Surg, Bloomington, IN USA

[16] Indiana Univ, Dept Pathol, Bloomington, IN USA

[17] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA

[18] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA

[19] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA

[20] Univ & Hosp Trust Verona, ARC Net Res Ctr, Dept Pathol & Diagnost, Verona, Italy

[21] Univ & Hosp Trust Verona, Dept Pathol Gen Surg B, Verona, Italy

[22] Univ & Hosp Trust Verona, Dept Surg, Verona, Italy

[23] Osped Sacro Cuore Don Calabraia, Dept Pathol, Negrar, Italy

[24] IRCCS San Raffaele Sci Inst, Dept Surg, Div Pancreat Surg, Milan, Italy

[25] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea

[26] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea

[27] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea

[28] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Hepatobiliary & Pancreas Surg, Seoul, South Korea

[29] St Vincents Univ Hosp, Dept Histopathol, Dublin 4, Ireland

[30] St Vincents Univ Hosp, Dept Surg, Dublin 4, Ireland

[31] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA

[32] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA

[33] Massachusetts Gen Hosp, Dept Histopathol, Boston, MA 02114 USA

[34] Univ Colorado, Dept Surg, Boulder, CO 80309 USA

[35] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA

[36] Hosp Curry Cabral, Ctr Hepatobiliopancreat & Transplantacao, Dept Pathol, Lisbon, Portugal

[37] Amsterdam Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[38] Natl Canc Ctr, Dept Hepatobiliary & Pancreat Surg Pathol & Canc, Tokyo, Japan

[39] Natl Canc Ctr, Tokyo, Japan

[40] Aichi Canc Ctr Hosp, Dept Gastroenterol, Nagoya, Aichi 464, Japan

[41] Univ Hosp KU Leuven, Dept Hepatol, Leuven, Belgium

[42] Johns Hopkins Univ, Dept Med, Baltimore, MD USA

来源：

GASTROENTEROLOGY | 2015年 / 149卷 / 06期

基金：

美国国家卫生研究院;

关键词：

Molecular; IPMN; Diagnosis; Pancreatic Cyst; PAPILLARY MUCINOUS NEOPLASMS; CLINICOPATHOLOGICAL FEATURES; UPDATED EXPERIENCE; PREVALENCE; MUTATIONS; CANCER; GENES; DNA;

D O I：

10.1053/j.gastro.2015.07.041

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND & AIMS: 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. METHODS: 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 was compared with that of clinical markers and a combination of molecular and clinical markers. RESULTS: 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%. CONCLUSIONS: 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.

引用

页码：1501 / 1510

页数：10

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