HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

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

Y.H. Xuan1,6, Y.L. Choi2, Y.K. Shin3,4, M.C. Kook7, S.W. Chae8, S.M. Park9, H.B. Chae9 and S.H. Kim1,5

1Department of Pathology, Chungbuk National University College of Medicine, 2Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 3Department of Pharmacy, Seoul National University College of Pharmacy, 4DiNonA Inc. Seoul, Korea, 5Chungbuk National University, Medical Research Institute, 6Department of Pathology, Yanbian University College of Medicine, China, 7Department of Pathology, Seoul National University College of Medicine, 8Department of Pathology, Sungkyunkwan University College of Medicine and 9Department of Internal Medicine, Chungbuk National University College of Medicine

Offprint requests to: Seok Hyung Kim, Department of Pathology, Chungbuk National University Hospital, 62 Kaesin-dong, Cheongju, Chungbuk, South Korea, 361-763. Fax: +82-043-269-6269. e-mail: platoshkim@freechal.com


Summary. 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. Histol Histopathol 20, 59-66 (2005)

Key words: Gallbladder, Immunohistochemistry, Cell cycle, p53, MSH2

DOI: 10.14670/HH-20.59

Y.H. Xuan and Y.L. Choi contributed equally