Oncotarget

Research Papers:

hERG1 behaves as biomarker of progression to adenocarcinoma in Barrett’s esophagus and can be exploited for a novel endoscopic surveillance

Elena Lastraioli, Tiziano Lottini, Jessica Iorio, Giancarlo Freschi, Marilena Fazi, Claudia Duranti, Laura Carraresi, Luca Messerini, Antonio Taddei, Maria Novella Ringressi, Marianna Salemme, Vincenzo Villanacci, Carla Vindigni, Anna Tomezzoli, Roberta La Mendola, Maria Bencivenga, Bruno Compagnoni, Mariella Chiudinelli, Luca Saragoni, Ilaria Manzi, Giovanni De Manzoni, Paolo Bechi, Luca Boni and Annarosa Arcangeli _

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Oncotarget. 2016; 7:59535-59547. https://doi.org/10.18632/oncotarget.11149

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Abstract

Elena Lastraioli1, Tiziano Lottini1, Jessica Iorio1, Giancarlo Freschi2, Marilena Fazi2, Claudia Duranti1, Laura Carraresi3, Luca Messerini1, Antonio Taddei2, Maria Novella Ringressi2, Marianna Salemme4, Vincenzo Villanacci4, Carla Vindigni5, Anna Tomezzoli6, Roberta La Mendola7, Maria Bencivenga7, Bruno Compagnoni8, Mariella Chiudinelli9, Luca Saragoni10, Ilaria Manzi11, Giovanni De Manzoni7, Paolo Bechi2, Luca Boni12,*, Annarosa Arcangeli1,*

1Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy

2Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy

3DI.V.A.L Toscana Srl, 50019 Sesto Fiorentino, Italy

4Institute of Pathology, Spedali Civili, 25123 Brescia, Italy

5Pathology Division, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy

6Pathology Division, Borgo Trento Hospital, 37134 Verona, Italy

7Division of Surgery, University of Verona, 37134 Verona, Italy

8Surgery Division, Esine Hospital, ASL Vallecamonica Sebino, 25040 Esine (BS), Italy

9Pathology Division, Esine Hospital, ASL Vallecamonica Sebino, 25040 Esine (BS), Italy

10Pathology Division, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy

11Gastroenterology and Endoscopy Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy

12Clinical Trials Coordinating Center, Azienda Ospedaliero-Universitaria Careggi/Istituto Toscano Tumori, 50134 Florence, Italy

*These authors contributed equally to this work

Correspondence to:

Annarosa Arcangeli, email: annarosa.arcangeli@unifi.it

Keywords: hERG1, Barrett’s esophagus, adenocarcinoma progression, surveillance, optical imaging

Received: March 13, 2016     Accepted: July 09, 2016     Published: August 09, 2016

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.


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