Pericentriolar material analyses in normal esophageal mucosa, Barrett's metaplasia and adenocarcinoma.
Barrett's esophagus metaplasia is a pre-cancerous condition caused by chronic esophagitis. Chromosomal instability (CIN) is common in Barrett's cells: therefore, we investigated the possible presence of centrosomal aberrations (a main cause of CIN) by centrosomal protein immunostaining in paraffined esophageal samples of patients who developed a Barrett's adenocarcinoma. In most (55%) patients, alterations of the pericentriolar material (PCM) signals were evident and consistently marked the transition between normal epithelium to metaplasia. The alterations could even be found in adjacent native squamous epithelium, Barrett's mucosa and submucosal gland cells, as well as in the basal/epibasal layers of the mucosa and submucosal gland duct, which are the regions hosting esophageal stem and progenitor cells. These findings strongly support the hypothesis that the three esophageal histotypes (one being pathological) can have a common progenitor. Surprisingly, PCM defective signal eventually decreased with neoplastic progression, possibly to enhance the genome stability of advanced cancer cells. Importantly, PCM altered signals in Barrett's mucosa and their apparent evolution in successive histopathological steps were correlated to adenocarcinoma aggressiveness, suggesting PCM as a possible prognostic marker for tumor relapse. Extending our observations in a prospective study might help in the development of new prevention protocols for adenocarcinoma patients.
Segat
Daniela
D
Proliferation Unit, Department of Biology, University of Padova, Italy.
Cassaro
Mauro
M
Dazzo
Emanuela
E
Cavallini
Lucia
L
Romualdi
Chiara
C
Salvador
Renato
R
Vitale
Maria Pia
MP
Vitiello
Libero
L
Fassan
Matteo
M
Rugge
Massimo
M
Zaninotto
Giovanni
G
Ancona
Ermanno
E
Baroni
Maurizio David
MD
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000378:metabolism; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018385:Centrosome / Q000378:metabolism* / Q000473:pathology; D043171:Chromosomal Instability; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D008954:Models, Biological; D009092:Mucous Membrane / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D014404:Tubulin / Q000378:metabolism
D000941:Antigens; D014404:Tubulin; C086178:pericentrin