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

Clin Cancer Res. 2019 May 15;25(10):3096-3103. doi: 10.1158/1078-0432.CCR-18-3388. Epub 2019 Jan 28.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology
  • Appendiceal Neoplasms / genetics*
  • Appendiceal Neoplasms / pathology
  • Biomarkers, Tumor / genetics*
  • Chromogranins / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Male
  • Microsatellite Instability*
  • Mutation*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Pseudomyxoma Peritonei / genetics
  • Pseudomyxoma Peritonei / pathology
  • Retrospective Studies


  • Biomarkers, Tumor
  • Chromogranins
  • KRAS protein, human
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs
  • Proto-Oncogene Proteins p21(ras)