COX-2, CDX2, and CDC2 immunohistochemical assessment for dysplasia-carcinoma progression in Barrett's esophagus.
BACKGROUND
Immunohistochemical changes associated with development of cancer in Barrett's esophagus offer potential areas of intervention to prevent and manage esophageal cancer.


OBJECTIVE
To assess the role of cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2/cyclin-dependent kinase 1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.


METHODS
Specimens from 46 patients with Barrett's esophagus (39% without dysplasia, 33% with dysplasia and 28% with adenocarcinoma) were stained for cyclooxygenase 2, caudal-type homeobox transcription factor 2 and cell division cycle 2.


RESULTS
Cyclooxygenase 2: No expression differences between groups were found, except for adenocarcinomas (p=0.04). Caudal-type homeobox transcription factor 2: Nuclear positivity decreased from Barrett's esophagus without dysplasia (71.6%), to Barrett's esophagus with low grade dysplasia (35.3%), to Barrett's esophagus with high grade dysplasia (17.14%); in adenocarcinoma these percentages were intermediate between high and low grade dysplasia (30.5%). Cell division cycle 2: Expression on deeper glandular structures was 40% in Barrett's esophagus without dysplasia, 55.47% in Barrett's esophagus with dysplasia, and 63.84% in adenocarcinoma, with no statistical differences between groups. Concerning cells of the superficial layer, Barrett's esophagus with low grade dysplasia expressed focal positivity (p=0.0001 vs. no dysplasia); Barrett's esophagus with high grade dysplasia displayed diffuse positivity (p=0.0001 vs. no dysplasia and low grade dysplasia). A diffuse positivity was found in Barrett's esophagus with adenocarcinoma (p=0.0001 vs. no dysplasia and low grade dysplasia).


CONCLUSIONS
Further evaluation of cyclooxygenase 2, cell division cycle 2 and caudal-type homeobox transcription factor 2, in association with morphology, might help to improve the accuracy of diagnosis and be useful for the clinical-pathological assessment of patients with Barrett's esophagus.
Villanacci
V
V
2nd Department of Pathology, Spedali Civili, University of Brescia, Italy. villanacci@spedalicivili.brescia.it
Rossi
E
E
Zambelli
C
C
Galletti
A
A
Cestari
R
R
Missale
G
G
Casa
D Della
DD
Bassotti
G
G
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D051546:Cyclooxygenase 2; D016203:CDC2 Protein Kinase