Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach.
OBJECTIVE
To study multiple gene expression patterns and their roles in the process of gastric carcinogenesis.


RESULTS
Using a high-throughput tissue microarray technique, 169 specimens from gastric carcinomas, precursor lesions and normal mucosa were immunostained on a series of tissue chips for p53, p21(WAF1/CIP1) cyclin E, Bcl-2, c-met and mucin 5AC expression. The overexpression of p53 was observed in 10.7% of low-grade dysplasia (LGD), 38.1% of high-grade dysplasia (HGD) and 39.6% of intestinal type gastric carcinoma (IGC). Expression of p21(WAF1/CIP1) was found in 47.6% of incomplete intestinal metaplasia (IM), 36.7% of dysplasia (Dys) and 29.5% of IGC. The overexpression of cyclin E was more frequently present in carcinomas than in Dys (P < 0.05); moreover, high-level expression (> 25% in extent) of cyclin E was observed only among IGC. Abnormal Bcl-2 expression was present in 81.0% of incomplete IM, 69.4% of Dys and 22.9% of IGC. Along with progression of the lesion, the expression of c-met increased; in contrast, mucin 5AC decreased gradually.


CONCLUSIONS
The specific expression pattern in incomplete IM was mucin 5AC+/Bcl-2+/p53-/cyclin E-, while mucin 5AC-/cyclin E+ was specific for IGC. p53 was useful for distinguishing LGD from HGD. High-level expression of cyclin E might be an indicator for malignant transformation of dysplasia.
Sun
Y
Y
Department of Pathology, Beijing Cancer Hospital, Beijing Institute for Cancer Research, Peking University School of Oncology, Beijing, China.
Li
J-Y
JY
He
J-S
JS
Zhou
L-X
LX
Chen
K
K
D018797:Cell Cycle Proteins / Q000032:analysis; D019927:Cyclin E / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D013270:Stomach / Q000737:chemistry / Q000473:pathology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019859:Proto-Oncogene Proteins c-met