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[Deletion mapping of chromosome 18q and Smad proteins expression analysis in urinary bladder carcinomas]
1Cancer Institute(Hospital), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Objective:
To investigate the role of loss of heterozygosity (LOH) on chromosome 18q in the carcinogenesis and progression of urinary bladder cancer and to provide clues for early detection and positional cloning of related genes.
Methods:
Deletion mapping was performed on 18q using 12 microsatellite markers. Immunohistochemistry staining was used to evaluate the expression level of two tumor suppressor candidates Smad 2 and Smad 4 in this region.
Results:
LOH in at least one of the 12 microsatellites on 18q was detected in 84.2% (32/38) of patients with bladder cancer. The minimal deletion region included tumor suppressor candidate Smad 4. Immunohistochemical study revealed that 21.1% (8/38) of the cases had up-regulated Smad 2 protein and 34.2% (13/38) of the cases had down-regulated Smad 2 protein. Smad4 protein expression was down-regulated in 68.4% (26/38) of the cases but up-regulated Smad 4 expression was seen in only one case.
Conclusions:
LOH on 18q was closely linked with bladder cancer. The irregular expression of tumor suppressor candidates Smad 2 and Smad 4 may play important role in the initiation and progression of bladder neoplasms.