Early Gastric Cancer: identification of molecular markers able to distinguish submucosa-penetrating lesions with different prognosis.

Autor: Molinari C; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Tedaldi G; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy. gianluca.tedaldi@irst.emr.it., Rebuzzi F; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Morgagni P; Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy., Capelli L; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Ravaioli S; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Tumedei MM; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Scarpi E; Biostatistics and Clinical Trials Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., Tomezzoli A; Department of Pathology, University of Verona, Verona, Italy., Bernasconi R; Department of Pathology, University of Verona, Verona, Italy., Ambrosio MR; Pathology Unit, University of Siena, Siena, Italy.; Pathology Unit, Azienda USL Toscana Nord-Ovest, Pisa, Italy., D'Ignazio A; Surgery Unit, University of Siena, Siena, Italy., Solaini L; Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy.; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy., Limarzi F; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Ercolani G; Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy., Martinelli G; Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., Ulivi P; Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014, Meldola, FC, Italy., Saragoni L; Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.
Jazyk: angličtina
Zdroj: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association [Gastric Cancer] 2021 Mar; Vol. 24 (2), pp. 392-401. Date of Electronic Publication: 2020 Nov 06.
DOI: 10.1007/s10120-020-01135-8
Abstrakt: 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 TP53 mut/LOH significantly characterized Pen A.
Databáze: MEDLINE
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