Molecular Profiling of Appendiceal Serrated Lesions, Polyps and Mucinous Neoplasms: a Single-centre Experience

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2021 Mar 13

PMID 33712927

Citations 6

Authors

Giada Munari

Gianluca Businello

Paola Mattiolo

Gianmaria Pennelli

Marta Sbaraglia

Chiara Borga

Salvatore Pucciarelli

Gaya Spolverato

Claudia Mescoli

Francesca Galuppini

Antonio Sommariva

Elena Bellan

Sara Lonardi

Fotios Loupakis

Claudio Luchini

Angelo Paolo Dei Tos

Matteo Fassan

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Gibson J, Pengelly R, Mirandari A, Boukas K, Stanford S, Cecil T Cancer Med. 2024; 13(20):e70340.

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The Vermiform Appendix and Its Pathologies.

Constantin M, Petrescu L, Matanie C, Vrancianu C, Niculescu A, Andronic O Cancers (Basel). 2023; 15(15).

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The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review.

Murage N, Ahmed N, Underwood T, Walters Z, Breininger S Cancer Metastasis Rev. 2023; 42(1):335-359.

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