Journal of cancer research and clinical oncology · 2021
Molecular profiling of appendiceal serrated lesions, polyps and mucinous neoplasms: a single-centre experience.
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Munari Giada, Businello Gianluca, Mattiolo Paola, Pennelli Gianmaria, Sbaraglia Marta, Borga Chiara, Pucciarelli Salvatore, Spolverato Gaya, Mescoli Claudia, Galuppini Francesca, Sommariva Antonio, Bellan Elena, Lonardi Sara, Loupakis Fotios, Luchini Claudio, Dei Tos Angelo Paolo, Fassan Matteo
Аннотация
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.
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.