Expression of cyclin B1 in the metaplasia-dysplasia-carcinoma sequence of Barrett esophagus.
BACKGROUND
It is known that proliferation is deregulated progressively during carcinogenesis in Barrett esophagus (BE). Cyclin B1 is a key protein for the regulation of G2-M-phase transition during the cell cycle and is essential for initiation of mitosis.


METHODS
Using immunohistochemistry, samples of Barrett metaplastic specialized epithelium (SE; n = 36 samples), low-grade dysplasia (LGD; n = 25 samples), high-grade dysplasia (HGD; n = 25 samples), and invasive adenocarcinoma (CA; n = 46 samples) derived from 50 esophagectomy specimens were investigated for the expression of cyclin B1. The number of cyclin B1 positive cells was determined semiquantitatively. In addition, in SE, LGD, and HGD samples, the pattern of cyclin B1 expression was assessed by determination of the presence of positive cells in four mucosal compartments: the deep glandular zone, the lower crypt zone, the upper crypt zone, and the luminal surface.


RESULTS
Cyclin B1 expression was found in all lesions under investigation. Regarding the percentage of positive cells, a marked increase of cyclin B1 positive cells was observed in SE samples compared with LGD samples and in HGD samples compared with CA samples (chi-square test; P < 0.0001), nevertheless showing a broad overlap between the different lesions. Concerning staining patterns, in the majority of SE samples (72.2%), cyclin B1 positive cells were restricted to the glandular zone and the lower crypt zone. In contrast, an expansion of cyclin B1 positive cells to superficially located zones of the mucosa (the upper crypt zone and/or the luminal surface) was observed in the majority of LGD samples (96.0%) and HGD samples (100%; P < 0.0001).


CONCLUSIONS
Overexpression of cyclin B1 is a frequent and early finding in the metaplasia-dysplasia-carcinoma sequence in BE. It may contribute to the loss of growth control and, subsequently, to the development of tumors in this location.
Geddert
Helene
H
Institute of Pathology, University of Düsseldorf, Düsseldorf, Germany.
Heep
Hans J
HJ
Gabbert
Helmut E
HE
Sarbia
Mario
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D008875:Middle Aged
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1