An immunohistochemical study
of the expression of cell-cycle-regulated
proteins p53, cyclin D1, RB, p27, Ki67 and MSH2
in gallbladder carcinoma and its precursor lesions
Gallbladder carcinomas are rare but highly
lethal neoplasms. We examined the expression of five
cell-cycle-related molecules (p53, RB, cyclin D1, p27,
Ki-67), and MSH2, in 46 carcinomas, 14 adenomas, 15
low-grade dysplasias, 9 intestinal metaplasias and 20
normal gallbladder epithelia. The expression of these
molecules was altered in gallbladder carcinomas and
adenomas. In gallbladder carcinomas we observed
increased expression of p53, cyclin D1, Ki-67, and
MSH2 together with decreased expression of RB and
p27 protein. Aberrant expression of cyclin D1 and
reduced expression of RB were noted in adenomas, and
expression of cyclin D1 was elevated in low-grade
dysplasias. However, there was no change in the levels
of these cell-cycle molecules in metaplasia. Expression
of p53, p27, Ki-67, and MSH2 was correlated with
clinical stage (P<0.05) and there was also a correlation
between the expression of Ki-67 and MSH-2 and patient
age (P<0.05). These results suggest that altered
expression of cell-cycle molecules p53, cyclin D1, RB,
p27, and of MSH-2 is involved in the progression of
gallbladder carcinomas