Retrospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2016; 22(11): 3202-3211
Published online Mar 21, 2016. doi: 10.3748/wjg.v22.i11.3202
Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?
Alfredo Di Leo, Gabriella Nesi, Mariabeatrice Principi, Domenico Piscitelli, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Francesco Tonelli
Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
Gabriella Nesi, Pathology Section, Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy
Domenico Piscitelli, Pathology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
Francesco Tonelli, General Surgery Section, Department of Surgery and Translational Medicine, University of Florence, 50134 Florence, Italy
Author contributions: Di Leo A, Ierardi E and Tonelli F conceived the study; Nesi G, Piscitelli D, Principi M, Iannone A and Losurdo G collected the data; Girardi B and Pricci M performed immunohistochemistry and confocal microscopy; Di Leo A and Ierardi E wrote the manuscript; all the authors read and approved the final version of the manuscript.
Institutional review board statement: The study was reviewed and approved after two meetings of all the authors before and after immune-histochemistry and confocal microscopy.
Informed consent statement: All study participants provided informed written consent prior to the endoscopic investigation or surgery; additional oral consent to perform immunohistochemistry or confocal microscopy was obtained.
Conflict-of-interest statement: No author received fees for this study. There is no conflict of interest.
Data sharing statement: No additional data are available. Moreover, the presented data are anonymized and risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Enzo Ierardi, Professor, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy. e.ierardi@virgilio.it
Telephone: +39-80-5592577 Fax: +39-80-5593088
Received: September 11, 2015
Peer-review started: September 15, 2015
First decision: November 27, 2015
Revised: December 14, 2015
Accepted: January 9, 2016
Article in press: January 9, 2016
Published online: March 21, 2016
Processing time: 184 Days and 13.8 Hours
Abstract

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis markers.

METHODS: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni’s test, and Pearson’s correlation test were applied for statistical analysis.

RESULTS: ER-beta showed a progressive decline: normal tissue (23.5 ± 4.9), LGD (21.1 ± 4.8), HGD (9.3 ± 3.5), AC (7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue (24.8 ± 5.6) to AC (52.0 ± 8.2); the expression in normal tissue was similar to controls (22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson’s correlation test showed a direct relationship between ER-β and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-β and caspase 3 declined progressively from normal to neoplastic tissue.

CONCLUSION: This study confirmed that ER-β is strongly decreased in duodenal FAP carcinomas, declining in a multiple step fashion, thereby suggesting a putative anti-carcinogenic effect. ER-α showed the opposite trend. ER-β/caspase 3 co-expression suggests this hormone’s possible involvement in apoptosis. Hormonal influences in FAP duodenal tumorigenesis, and modulation of these as a possible chemoprevention strategy, may be a promising approach.

Keywords: Familial adenomatous polyposis; Duodenal cancer; Estrogen receptors; Immunohistochemistry; Confocal microscopy; Dysplasia

Core tip: Familial adenomatous polyposis (FAP) is a genetically inherited disease featuring multiple colonic polyps, with possible duodenal involvement. No study investigating the relationship between estrogen receptors (ERs) and cellular turnover has previously been reported in duodenal FAP patient’s subset. In the present study we found that ER-β is strongly decreased in duodenal FAP carcinomas, in a multiple step fashion suggesting a putative anti-carcinogenic effect. ER-α shows the opposite trend. A possible ER-beta involvement in apoptosis is suggested by its co-expression with caspase-3. The modulation of hormonal influences in FAP duodenal tumorigenesis as a possible chemoprevention strategy may be a promising approach.