Mucin expression profile in Barrett's, dysplasia, adenocarcinoma sequence in the esophagus.
BACKGROUND
The molecular events that accompany the progression to adenocarcinoma (ADC) of the esophagus are poorly understood. Aberrant mucin receptor expression can contribute to increased cell growth and metastatic ability.


OBJECTIVE
The aim of this study was to establish a pattern for mucin (MUC) gene expression in the esophageal mucosa under normal and pathological conditions.


METHODS
University Hospital Cancer Center Laboratory. Archived tissue samples studied in a retrospective fashion.


METHODS
Tissue samples were obtained from the archives of patients with histological evidence of Barrett's esophagus (BE) progressing to ADC. Immunohistochemical analysis was performed using mouse monoclonal antibodies for MUC1, MUC2, MUC5AC, MUC6. Semiquantitative scoring of histological staining was performed using a linear scoring system: 0-staining absent; 1-staining in 0-25%; 2-staining in 25-50%; and 3-staining in 50-75% of the epithelium. The Binomial test was used to explore trends and differences in frequency of mucin expression along the pathological sequence.


RESULTS
Only mild superficial staining of MUC1 was seen in normal squamous epithelium. MUC1 and MUC2 were uniformly expressed in all samples (7/7) of BE and dysplasia (P=0.008). MUC1 expression was upregulated (7/7) in progression to adenocarcinoma (P=0.008). The secretory mucins, MUC5AC and MUC6 showed a decrease in expression with progression from BE to dysplasia to ADC (P< 0.05).


CONCLUSIONS
Downregulation of MUC5AC and MUC6 decreases mucosal protection against gastric acid. Increasing MUC1 expression is associated with progression from dysplasia to ADC. Upregulation of MUC2 reflects intestinal metaplasia in BE.
Burjonrappa
S C
SC
Department of Surgical Oncology, Creighton University, Omaha, NE 68131, USA. sathyabc@yahoo.com
Reddimasu
S
S
Nawaz
Z
Z
Gao
X
X
Sharma
P
P
Loggie
B
B
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000378:metabolism; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; C524626:Muc2 protein, mouse; C524679:Muc5ac protein, mouse; C524735:Muc6 protein, mouse; D055271:Mucin 5AC; D018396:Mucin-1; D055262:Mucin-2; D055272:Mucin-6; D009077:Mucins