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

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...

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Published in:	World journal of gastroenterology : WJG 2016-03, Vol.22 (11), p.3202-3211
Main Authors:	Di Leo, Alfredo, Nesi, Gabriella, Principi, Mariabeatrice, Piscitelli, Domenico, Girardi, Bruna, Pricci, Maria, Losurdo, Giuseppe, Iannone, Andrea, Ierardi, Enzo, Tonelli, Francesco
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma - chemistry Adenocarcinoma - pathology Adenocarcinoma - surgery adenomatous Adenomatous Polyposis Coli - chemistry Adenomatous Polyposis Coli - pathology Adenomatous Polyposis Coli - surgery Adult Apoptosis Biomarkers, Tumor - analysis cancer Estrogen Caspase 3 - analysis Cell Proliferation Duodenal Neoplasms - chemistry Duodenal Neoplasms - pathology Duodenal Neoplasms - surgery Duodenum - chemistry Duodenum - pathology Duodenum - surgery Estrogen Receptor alpha - analysis Estrogen Receptor beta - analysis Familial Female Humans Intestinal Mucosa - chemistry Intestinal Mucosa - pathology Intestinal Mucosa - surgery Ki-67 Antigen - analysis Male micr Middle Aged polyposis Duodenal receptors Immunohistochemistry Confocal Retrospective Studies Retrospective Study Young Adult
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Summary:	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-b 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-b and caspase 3 declined progressively from normal to neoplastic tissue.CONCLUSION: This study confirmed that ER-b 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-b/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.
ISSN:	1007-9327 2219-2840