Early Gastric Cancer: identification of molecular markers able to distinguish submucosa-penetrating lesions with differe
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ORIGINAL ARTICLE
Early Gastric Cancer: identification of molecular markers able to distinguish submucosa‑penetrating lesions with different prognosis Chiara Molinari1 · Gianluca Tedaldi1 · Francesca Rebuzzi1 · Paolo Morgagni2 · Laura Capelli1 · Sara Ravaioli1 · Maria Maddalena Tumedei1 · Emanuela Scarpi3 · Anna Tomezzoli4 · Riccardo Bernasconi4 · Maria Raffaella Ambrosio5,6 · Alessia D’Ignazio7 · Leonardo Solaini2,8 · Francesco Limarzi1 · Giorgio Ercolani2 · Giovanni Martinelli9 · Paola Ulivi1 · Luca Saragoni10 Received: 4 August 2020 / Accepted: 18 October 2020 © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2020
Abstract Background Early Gastric Cancer (EGC) reaches 25% of the gastric cancers surgically treated in some areas of Northeastern Italy and is usually characterized by a good prognosis. However, among EGCs classified according to Kodama’s criteria, Pen A subgroup is characterized by extensive submucosal invasion, lymph node metastases and worse prognosis, whereas Pen B subgroup by better prognosis. The aim of the study was to characterize the differences between Pen A, Pen B and locally advanced gastric cancer (T3N0) in order to identify biomarkers involved in aggressiveness and clinical outcome. Methods We selected 33 Pen A, 34 Pen B and 20 T3N0 tumors and performed immunohistochemistry of mucins, copy number variation analysis of a gene panel, microsatellite instability (MSI), TP53 mutation and loss of heterozygosity (LOH) analyses. Results Pen A subgroup was characterized by MUC6 overexpression (p = 0.021). Otherwise, the Pen B subgroup was significantly associated with the amplification of GATA6 gene (p = 0.002). The higher percentage of MSI tumors was observed in T3N0 group (p = 0.002), but no significant differences between EGC types were found. Finally, TP53 gene analysis showed that 32.8% of Pen tumors have a mutation in exons 5–8 and 50.0% presented LOH. Co-occurrence of TP53 mutation and LOH mainly characterized Pen A tumors (p = 0.022). Conclusions Our analyses revealed that clinico-pathological parameters, microsatellite status and frequency of TP53 mutations do not seem to distinguish Pen subgroups. Conversely, the amplification of GATA6 was associated with Pen B, as well as the overexpression of MUC6 and the TP53mut/LOH significantly characterized Pen A. Keywords Early Gastric Cancer · Submucosa-penetrating tumors · MUC6 · GATA6 · TP53 Paola Ulivi and Luca Saragoni Contributed equally Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10120-020-01135-8) contains supplementary material, which is available to authorized users. 5
Pathology Unit, University of Siena, Siena, Italy
6
Pathology Unit, Azienda USL Toscana Nord-Ovest, Pisa, Italy
7
Surgery Unit, University of Siena, Siena, Italy
8
Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
9
3
Biostatistics and Clinical Trial
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