Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

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.

• Authors: Alfredo Di Leo, Gabriella Nesi, Mariabeatrice Principi, Domenico Piscitelli, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Francesco Tonelli
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 22 Issue 11 Pg. 3202-11 (Mar 21 2016) ISSN: 2219-2840 [Electronic] United States
• PMID: 27003997 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• ESR1 protein, human
• ESR2 protein, human
• Estrogen Receptor alpha
• Estrogen Receptor beta
• Ki-67 Antigen
• CASP3 protein, human
• Caspase 3

Topics

• Adenocarcinoma (chemistry, pathology, surgery)
• Adenomatous Polyposis Coli (chemistry, pathology, surgery)
• Adult
• Apoptosis
• Biomarkers, Tumor (analysis)
• Caspase 3 (analysis)
• Cell Proliferation
• Duodenal Neoplasms (chemistry, pathology, surgery)
• Duodenum (chemistry, pathology, surgery)
• Estrogen Receptor alpha (analysis)
• Estrogen Receptor beta (analysis)
• Female
• Humans
• Intestinal Mucosa (chemistry, pathology, surgery)
• Ki-67 Antigen (analysis)
• Male
• Middle Aged
• Retrospective Studies
• Young Adult