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Elena Lastraioli,1 Maria Raffaella Romoli,1 Jessica Iorio,1 Tiziano Lottini,1 Mariella Chiudinelli,2 Maria Bencivenga,3 Carla Vindigni,4 Anna Tomezzoli,5 Giovanni De Manzoni,3 Bruno Compagnoni,6 Ilaria Manzi,7 Luca Messerini,1 Luca Saragoni,8 Annarosa Arcangeli1 On behalf of Gruppo Italiano di Ricerca Cancro Gastrico (GIRCG)1Department of Experimental and Clinical Medicine, Section of Internal Medicine, University Of Florence, Florence 50134, Italy; 2Pathology Division, Esine Hospital, ASST della Valcamonica, Esine, BS 25040, Italy; 3Surgery Division, University of Verona, Verona 37134, Italy; 4Pathology Division, Azienda Ospedaliero-Universitaria Senese, Siena 53100, Italy; 5Pathology Division, Borgo Trento Hospital, Verona 37134, Italy; 6Surgery Division, Esine Hospital, ASST della Valcamonica, Esine, BS 25040, Italy; 7Gastroenterology and Endoscopy Unit, Morgagni-Pierantoni Hospital, Forlì 47121, Italy; 8Pathology Division, Morgagni-Pierantoni Hospital, Forlì 47121, ItalyCorrespondence: Elena LastraioliDepartment of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Viale GB Morgagni, 50, Florence 50134, ItalyTel +39 055 2751319Fax +39 055 2751281Email elena.lastraioli@unifi.itPurpose: Gastric cancer (GC) is still a relevant health issue worldwide. The identification of prognostic factors for progression of gastric dysplasia (GD), the main pre-cancerous lesion of the intestinal-type GC, is hence mandatory.Patients and methods: A cohort of 83 GD endoscopic samples belonging to Italian subjects was collected. hERG1 expression was evaluated by immunohistochemistry and scored 0–3, depending on the percentage of stained cells. Expression data were analysed in conjunction with clinico-pathological and survival data.Results: hERG1 turned out to be expressed in 67.47% (56 out of 83) of the GD samples. hERG1 expression was higher in high-grade GD compared to low-grade GD (29 out of 39, 74.36% vs 27 out of 44, 61.36%), although the statistical significance was not reached (P=0.246). No association emerged between hERG1 expression and clinical features of the patients (age, gender, localization, H. pylori infection, gastritis and intestinal metaplasia). In a subset of cases for which sequential samples of gastric lesions (from GD to Early Gastric Cancer and Advanced Gastric Cancer) were available, hERG1 expression was maintained in all the steps of gastric carcinogenesis from GD onwards. A general trend to increased expression in advanced lesions was observed. hERG1 score had a statistically significant impact on both Progression-Free Survival (P=0.018) and Overall Survival (P=0.031). In particular, patients displaying a high hERG1 score have a shorter survival.Conclusion: hERG1 is aberrantly expressed in human GD samples and has an impact on both PFS and OS, hence representing a novel prognostic marker for progression of GD towards GC of the intestinal histotype. Once properly validated, hERG1 detection could be included in the clinical practice, during endoscopic surveillance protocols, for the management of GD at higher risk of progression, as already proposed for Barrett’s oesophagus.Keywords: Kv11.1, immunohistochemistry, endoscopic surveillance in gastric dysplasia, prognosis, intestinal type gastric adenocarcinoma |
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