Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience

J Cancer Res Clin Oncol. 2021 Jul;147(7):1897-1904. doi: 10.1007/s00432-021-03589-4. Epub 2021 Mar 12.


Purpose: Non-neuroendocrine neoplasms of the appendix are a phenotypically heterogeneous group of lesions; a comprehensive molecular characterization of these tumors is still lacking.

Methods: A total of 52 samples taken from 49 patients was evaluated: 18 sessile serrated lesions (SSL; 3 with dysplasia), 2 high-grade tubular adenomas, 1 tubulo-villous adenoma,1 hyperplastic polyp, 18 low-grade appendiceal mucinous neoplasms (LAMN), 3 high-grade appendiceal mucinous neoplasms (HAMN) and 9 mucinous adenocarcinomas. Hotspot mutational profiling of the RNF43, SMAD4, KRAS, NRAS, BRAF and PIK3CA genes was performed. Expression of p53, MLH1, PMS2, MSH2, and MSH6 was evaluated by immunohistochemistry.

Results: KRAS was the most frequently mutated gene (53.9% of cases), followed by RNF43 (15.4%), and BRAF (13.5%). In particular: KRAS was mutated in 44.4% of adenocarcinomas, 66.7% of HAMNs, 61.1% of LAMNs, 53.3% of SSL without dysplasia and in 66.7% of SSL with dysplasia; RNF43 was mutated in 33.3% of adenocarcinomas, 66.7% of HAMNs, 11.1% of LAMNs and in 6.7% of SSL without dysplasia; BRAF was mutated in 11.1% of adenocarcinomas, 26.7% of SSL without dysplasia and in 5.6% of LAMNs. Only a case of high-grade tubular adenoma showed mismatch repair deficiency, while immunohistochemical expression of p53 was altered in 21.1% of cases.

Conclusions: The histological phenotypic similarities between appendicular mucinous lesions and serrated colon lesions do not reflect a similar genetic landscape. Mismatch repair deficiency is a rare event during appendiceal mucinous carcinogenesis.

Keywords: Appendiceal neoplasms; Biomarkers; Molecular pathology; Pseudomyxoma peritonei; Serrated lesions.

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / pathology*
  • Aged
  • Appendiceal Neoplasms / genetics
  • Appendiceal Neoplasms / pathology*
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis / methods*
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation*
  • Polyps / genetics
  • Polyps / pathology*
  • Prognosis


  • Biomarkers, Tumor