Publications

Authors:

Angerilli, Valentina; Vanoli, Alessandro; Celin, Giulia; Ceccon, Carlotta; Gasparello, Jessica; Sabbadin, Marianna; De Lisi, Giuseppe; Paudice, Michele; Lenti, Marco Vincenzo; Rovedatti, Laura; Di Sabatino, Antonio; Bazzocchi, Francesca; Lonardi, Sara; Savarino, Edoardo; Luchini, Claudio; Parente, Paola; Grillo, Federica; Mastracci, Luca; Fassan, Matteo

Title:

Gastric carcinoma in autoimmune gastritis: a histopathologic and molecular study

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

Modern Pathology

ISSN of journal:

0893-3952

N° Volume:

37

Number or Folder:

6

Page numbers:

1-11

Keyword:

autoimmune gastritis; biomarkers; gastric cancer; genomic profiling

Short description of contents:

: Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathological and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from four Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, Mismatch Repair (MMR) proteins, and p53 and EBER in situ hybridization were performed. Histologic features and IHC were jointly reviewed by five expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%), were located in the corpus/fundus (58%) and were associated with OLGA stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia and ECL-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 Combined Positive Score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) MSI cases and 7 (37%) TMB-high. The most frequently altered genes were: TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [two amplified and five mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with long-standing misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB-high.

Product ID:

138939

Handle IRIS:

11562/1124146

Last Modified:

June 13, 2024

Bibliographic citation:

Angerilli, Valentina; Vanoli, Alessandro; Celin, Giulia; Ceccon, Carlotta; Gasparello, Jessica; Sabbadin, Marianna; De Lisi, Giuseppe; Paudice, Michele; Lenti, Marco Vincenzo; Rovedatti, Laura; Di Sabatino, Antonio; Bazzocchi, Francesca; Lonardi, Sara; Savarino, Edoardo; Luchini, Claudio; Parente, Paola; Grillo, Federica; Mastracci, Luca; Fassan, Matteo, Gastric carcinoma in autoimmune gastritis: a histopathologic and molecular study «Modern Pathology» , vol. 37 , n. 6 , 2024 , pp. 1-11

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