Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer

被引：70

作者：

Tokunaga, Ryuma ^{[1
]}

Xiu, Joanne ^{[2
]}

Johnston, Curtis ^{[2
]}

Goldberg, Richard M. ^{[3
]}

Philip, A. Philip ^{[4
]}

Seeber, Andreas ^{[5
]}

Naseem, Madiha ^{[1
]}

Lo, Jae Ho ^{[1
]}

Arai, Hiroyuki ^{[1
]}

Battaglin, Francesca ^{[1
]}

Puccini, Alberto ^{[1
]}

Berger, Martin D. ^{[1
]}

Soni, Shivani ^{[1
]}

Zhang, Wu ^{[1
]}

Hwang, Jimmy J. ^{[6
]}

Shields, Anthony F. ^{[4
]}

Marshall, John L. ^{[7
]}

Baba, Hideo ^{[8
]}

Korn, W. Michael ^{[2
]}

Lenz, Heinz-Josef ^{[1
]}

机构：

[1] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Div Med Oncol, Los Angeles, CA 90033 USA

[2] Caris Life Sci, Phoenix, AZ USA

[3] West Virginia Univ, Canc Inst, Morgantown, WV 26506 USA

[4] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA

[5] Med Univ Innsbruck, Dept Haematol & Oncol, Innsbruck, Austria

[6] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA

[7] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Ruesch Ctr Cure Gastrointestinal Canc, Washington, DC 20007 USA

[8] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto, Japan

来源：

CLINICAL CANCER RESEARCH | 2019年 / 25卷 / 10期

关键词：

PAPILLARY MUCINOUS NEOPLASMS; FREQUENT GNAS MUTATIONS; PSEUDOMYXOMA PERITONEI; LOW-GRADE; PREDICTIVE BIOMARKERS; CHEMOTHERAPY; CARCINOMATOSIS; INHIBITOR; ADENOMA; GENERATION;

D O I：

10.1158/1078-0432.CCR-18-3388

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: The natural history and prognosis of appendiceal adenocarcinomas differ from those of adenocarcinomas arising in other large bowel sites. We aimed to compare the molecular profiles exhibited by appendiceal adenocarcinomas and colorectal cancers, or between the histopathologic subtypes of appendiceal adenocarcinoma. Experimental Design: A total of 183 samples from appendiceal adenocarcinoma [46 adenocarcinoma, not otherwise specified (NOS), 66 pseudomyxoma peritonei (PMP), 44 mucinous adenocarcinoma (MU), and 27 signet ring cell carcinoma (SR)], 994 from right-sided colorectal cancer (R-CRC), and 1,080 from left-sided CRC (L-CRC) were analyzed by next-generation sequencing (NGS) and IHC markers. Microsatellite instability (MSI) and tumor mutational burden (TMB) were tested by NGS, and programmed death ligand 1 (PD-L1) by IHC. Results: We observed high mutation rates in appendiceal adenocarcinoma samples for KRAS (55%), TP53 (40%), GNAS (31%), SMAD4 (16%), and APC (10%). Appendiceal adenocarcinoma exhibited higher mutation rates in KRAS and GNAS, and lower mutation rates in TP53, APC, and PIK3CA (6%) than colorectal cancers. PMP exhibited much higher mutation rates in KRAS (74%) and GNAS (63%), and much lower mutation rates in TP53 (23%), APC (2%), and PIK3CA (2%) than NOS. Alterations associated with immune checkpoint inhibitor response (MSI-high, TMB-high, PD-L1 expression) showed similar frequency in appendiceal adenocarcinoma compared with L-CRC, but not R-CRC, and those of NOS were higher than other subtypes of appendiceal adenocarcinoma and L-CRC. Conclusions: Molecular profiling of appendiceal adenocarcinoma revealed different molecular characteristics than noted in R-CRC and L-CRC, and molecular heterogeneity among the histopathologic subtypes of appendiceal adenocarcinoma. Our findings may be critical to developing an individualized approach to appendiceal adenocarcinoma treatment.

引用

页码：3096 / 3103

页数：8

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