title: hERG1 behaves as biomarker of progression to adenocarcinoma in Barrett's esophagus and can be exploited for a novel endoscopic surveillance.
abstract: Barrett's esophagus (BE) is the only well-known precursor lesion of esophageal adenocarcinoma (EA). The exact estimates of the annual progression rate from BE to EA vary from 0.07% to 3.6%. The identification of BE patients at higher risk to progress to EA is hence mandatory, although difficult to accomplish. In search of novel BE biomarkers we analyzed the efficacy of hERG1 potassium channels in predicting BE progression to EA. Once tested by immunohistochemistry (IHC) on bioptic samples, hERG1 was expressed in BE, and its expression levels increased during progression from BE to esophageal dysplasia (ED) and EA. hERG1 was also over-expressed in the metaplastic cells arising in BE lesions obtained in different BE mouse models, induced either surgically or chemically. Furthermore, transgenic mice which over express hERG1 in the whole gastrointestinal tract, developed BE lesions after an esophago-jejunal anastomosis more frequently, compared to controls. A case-control study was performed on 104 bioptic samples from newly diagnosed BE patients further followed up for at least 10 years. It emerged a statistically significant association between hERG1 expression status and risk of progression to EA. Finally, a novel fluorophore- conjugated recombinant single chain variable fragment antibody (scFv-hERG1-Alexa488) was tested on freshly collected live BE biopsies: it could recognize hERG1 positive samples, perfectly matching IHC data.Overall, hERG1 can be considered a novel BE biomarker to be exploited for a novel endoscopic surveillance protocol, either in biopsies or through endoscopy, to identify those BE patients with higher risk to progress to EA.
authors: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors: Elena
authors: E
authors: Lastraioli
authors: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors: Tiziano
authors: T
authors: Lottini
authors: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors: Jessica
authors: J
authors: Iorio
authors: Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
authors: Giancarlo
authors: G
authors: Freschi
authors: Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
authors: Marilena
authors: M
authors: Fazi
authors: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors: Claudia
authors: C
authors: Duranti
authors: DI.V.A.L Toscana Srl, 50019 Sesto Fiorentino, Italy.
authors: Laura
authors: L
authors: Carraresi
authors: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors: Luca
authors: L
authors: Messerini
authors: Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
authors: Antonio
authors: A
authors: Taddei
authors: Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
authors: Maria Novella
authors: MN
authors: Ringressi
authors: Institute of Pathology, Spedali Civili, 25123 Brescia, Italy.
authors: Marianna
authors: M
authors: Salemme
authors: Institute of Pathology, Spedali Civili, 25123 Brescia, Italy.
authors: Vincenzo
authors: V
authors: Villanacci
authors: Pathology Division, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
authors: Carla
authors: C
authors: Vindigni
authors: Pathology Division, Borgo Trento Hospital, 37134 Verona, Italy.
authors: Anna
authors: A
authors: Tomezzoli
authors: Division of Surgery, University of Verona, 37134 Verona, Italy.
authors: Roberta
authors: R
authors: La Mendola
authors: Division of Surgery, University of Verona, 37134 Verona, Italy.
authors: Maria
authors: M
authors: Bencivenga
authors: Surgery Division, Esine Hospital, ASL Vallecamonica Sebino, 25040 Esine (BS), Italy.
authors: Bruno
authors: B
authors: Compagnoni
authors: Pathology Division, Esine Hospital, ASL Vallecamonica Sebino, 25040 Esine (BS), Italy.
authors: Mariella
authors: M
authors: Chiudinelli
authors: Pathology Division, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
authors: Luca
authors: L
authors: Saragoni
authors: Gastroenterology and Endoscopy Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
authors: Ilaria
authors: I
authors: Manzi
authors: Division of Surgery, University of Verona, 37134 Verona, Italy.
authors: Giovanni
authors: G
authors: De Manzoni
authors: Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy.
authors: Paolo
authors: P
authors: Bechi
authors: Clinical Trials Coordinating Center, Azienda Ospedaliero-Universitaria Careggi/Istituto Toscano Tumori, 50134 Florence, Italy.
authors: Luca
authors: L
authors: Boni
authors: Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
authors: Annarosa
authors: A
authors: Arcangeli
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis*; D000818:Animals; D001471:Barrett Esophagus / Q000175:diagnosis*; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D004724:Endoscopy; D004938:Esophageal Neoplasms / Q000175:diagnosis*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011379:Prognosis; D012306:Risk
chemical_list: D015415:Biomarkers; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human
keywords: Barrett’s esophagus; adenocarcinoma progression; hERG1; optical imaging; surveillance