Cell proliferation and ultrastructural changes of the duodenal mucosa of patients affected by familial adenomatous polyposis.
Patients affected by familial adenomatous polyposis (FAP) are at risk of developing duodenal neoplasia. Our objective was to detect early abnormalities of the epithelial cell proliferation and ultrastructure of apparently normal duodenal mucosa of FAP patients. Biopsy specimens were taken from the duodenal mucosa. Cell proliferation was studied by immunohistochemistry with proliferating cell nuclear antigen (PCNA), and ultrastructure, by transmission electron microscopy. We found that the PCNA labeling index for duodenal mucosa of patients with FAP was higher in comparison to the case of hospital controls without cancer risk (P = 0.019). Moreover, ultrastructural changes related to an impairment of cell adhesion function were found in all biopsies of FAP patients but not in the duodenal mucosa of the controls. We conclude that alterations of cell proliferation kinetics and epithelial adherens junction structures were phenotypic characteristics of histologically normal duodenal mucosa of FAP patients. These abnormalities may be considered as intermediate biomarkers of neoplasia and potential surrogate endpoints in chemoprevention studies.
Biasco
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G
Istituto di Ematologia ed Oncologia Medica L.A. Seragnoli, Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Bologna, Italy.
Cenacchi
G
G
Nobili
E
E
Pantaleo
M A
MA
Calabrese
C
C
Di Febo
G
G
Morselli Labate
A
A
Miglioli
M
M
Brandi
G
G
D011125:Adenomatous Polyposis Coli / Q000473:pathology* / Q000648:ultrastructure*; D022005:Adherens Junctions / Q000473:pathology / Q000648:ultrastructure; D000328:Adult; D002455:Cell Division / Q000502:physiology; D004386:Duodenum / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen