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Gut. 1998 December; 43(6): 798–805. | PMCID: PMC1727344 |
Urokinase type plasminogen activator receptor expression in
colorectal neoplasms S Suzuki, Y Hayashi, Y Wang, T Nakamura, Y Morita, K Kawasaki, K Ohta, N Aoyama, S Kim, H Itoh, Y Kuroda, and W Doe First Division of Pathology, Kobe University School of Medicine, Kobe, Japan. Background—The urokinase type plasminogen
activator receptor (uPAR) may play a critical role in cancer invasion
and metastasis.
Aims—To study the involvement of uPAR in
colorectal carcinogenesis.
Methods—The cellular expression and localisation
of uPAR were investigated in colorectal adenomas and invasive
carcinomas by in situ hybridisation, immunohistochemistry, and northern
and western blot analyses.
Results—uPAR mRNA expression was found mainly in
the cytoplasm of dysplastic epithelial cells of 30% of adenomas with
mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A
(72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR
was detected in dysplastic epithelial cells of 14% of adenomas and in
carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and
protein concentrations were significantly higher in severe than in mild
or moderate dysplasia (p<0.05); they were notably higher in Dukes'
stage A than in severe dysplasia (p<0.05), and significantly higher in
Dukes' stage B than in stage A (p<0.05), but those in stage B were
not different from those in stage C or in metastatic colorectal
carcinomas of the liver.
Conclusions—Colorectal adenoma uPAR, expressed
essentially in dysplastic epithelial cells, was upregulated with
increasing severity of atypia, and increased notably during the
critical transition from severe dysplasic adenoma to invasive
carcinoma. These findings implicate uPAR expression in the invasive and
metastatic processes of colorectal cancer.
Keywords:
urokinase type plasminogen activator receptor; colorectal adenoma; colorectal cancer; adenoma-carcinoma sequence
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