MicroRNA Expression Profiling in the Histological Subtypes... : Clinical and Translational Gastroenterology (original) (raw)

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MicroRNA Expression Profiling in the Histological Subtypes of Barrett's Metaplasia

Fassan, Matteo MD1,2; Volinia, Stefano MD3; Palatini, Jeff PhD3; Pizzi, Marco MD1; Fernandez-Cymering, Cecilia PhD3; Balistreri, Mariangela BD1; Realdon, Stefano MD4; Battaglia, Giorgio MD4; Souza, Rhonda MD5; Odze, Robert D MD, FACG, FRCPc6; Zaninotto, Giovanni MD7; Croce, Carlo M MD3; Rugge, Massimo MD, FACG1,4

1Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy

2Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), General Oncology Unit, University of Padua, Padua, Italy

3Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA

4Istituto Oncologico Veneto - IOV-IRCCS, Padua, Italy

5Department of Medicine, University of Texas Southwestern Medical Center and VA North Texas Health Care System, Dallas, Texas, USA

6Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA

7Department of Surgical Oncology and Gastroenterology Sciences (DiSCOG), Surgery Unit, University of Padua, Padua, Italy

*Correspondence: Massimo Rugge, MD, FACG, Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Istituto Oncologico Veneto-IRCCS; Via Aristide Gabelli, 61, 35121 Padua, Italy. E-mail: [email protected]

Received 4 October 12; revised 21 February 13; accepted 29 March 13

published online 16 May 2013

Clinical and Translational Gastroenterology 4(5):p e34, May 2013. | DOI: 10.1038/ctg.2013.5

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Abstract

OBJECTIVES:

The histological definition of Barrett's esophagus (BE) is debated, particularly regarding the phenotype of its metaplastic columnar epithelium. Histologically proven intestinal metaplasia (IM) was the sine qua non condition for a diagnosis of BE but, more recently, non-intestinalized (i.e., cardiac gastric-type; GM) columnar metaplasia has been re-included in the spectrum of Barrett's histology. MicroRNAs modulate cell commitment, and are also reportedly dysregulated in Barrett's carcinogenesis. This study investigates miRNA expression in the histological spectrum of esophageal columnar metaplastic changes, specifically addressing the biological profile of GM vs. IM.

METHODS:

A study was performed to discover microRNA microarray in 30 matching mucosa samples obtained from 10 consecutive BE patients; for each patient, biopsy tissue samples were obtained from squamous, GM and intestinalized epithelium. Microarray findings were further validated by qRT-PCR analysis in another bioptic series of 75 mucosa samples.

RESULTS:

MicroRNA profiling consistently disclosed metaplasia-specific microRNA signatures. Six microRNAs were significantly dysregulated across the histological phenotypes considered; five of them (two overexpressed (hsa-miR-192; -miR-215) and three under-expressed (hsa-miR-18a*; -miR-203, and -miR-205)) were progressively dysregulated in the phenotypic sequence from squamous to gastric-type, to intestinal-type mucosa samples.

CONCLUSIONS:

A consistent microRNA expression signature underlies both gastric- and intestinal-type esophageal metaplasia. The pattern of microRNA dysregulation suggests that GM may further progress to IM. The clinico-pathological implications of these molecular profiles prompt further study on the “personalized” cancer risk associated with each of these metaplastic transformations.