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

Tokunaga, Ryuma; Xiu, Joanne; Johnston, Curtis; Goldberg, Richard M; Philip, Philip A; Seeber, Andreas; Naseem, Madiha; Lo, Jae Ho; Arai, Hiroyuki; Battaglin, Francesca; Puccini, Alberto; Berger, Martin D.; Soni, Shivani; Zhang, Wu; Hwang, Jimmy J; Shields, Anthony F; Marshall, John L; Baba, Hideo; Korn, W Michael and Lenz, Heinz-Josef (2019). Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer. Clinical cancer research, 25(10), pp. 3096-3103. American Association for Cancer Research 10.1158/1078-0432.CCR-18-3388

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1078-0432

Publisher:

American Association for Cancer Research

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

26 Aug 2020 17:01

Last Modified:

26 Aug 2020 17:09

Publisher DOI:

10.1158/1078-0432.CCR-18-3388

PubMed ID:

30692096

BORIS DOI:

10.7892/boris.146081

URI:

https://boris.unibe.ch/id/eprint/146081

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