Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis |
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Authors: | Takao Itoi Yasushi Shinohara Kazuya Takeda Kazuto Nakamura Kazuo Takei Jun Sanada Toshiya Horibe Toshihiko Saito Kazuhiko Kasuya Yoshirou Ebihara |
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Affiliation: | (1) Fourth Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan, JP;(2) Third Department of Surgery, Tokyo Medical University, Tokyo, Japan, JP;(3) First Department of Pathology, Tokyo Medical University, Tokyo, Japan, JP |
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Abstract: | Cyclin D1 overexpression is remarkably frequent in several human carcinomas and is believed to be a critical event in oncogenesis. We examined cyclin D1 expression, p53 expression, and the Ki-67 labeling index by immunostaining in human gallbladder mucosa in conditions varying from normal to malignant tissue. We also examined K-ras codon 12 mutations in these tissues with a two-step polymerase chain reaction. Nuclear cyclin D1 overexpression was observed in 48% of carcinomas occurring independently of adenoma, but not in adenomas, carcinomas arising in adenomas, or nonneoplastic lesions. Cytoplasmic cyclin D1 overexpression was observed in about 15% of abnormal specimens, irrespective of the type of epithelial abnormality. Carcinomas showing nuclear cyclin D1 overexpression had significantly higher Ki-67 labeling indexes than those with no overexpression. Moderately to poorly differentiated adenocarcinomas showed a higher incidence of nuclear cyclin D1 overexpression than papillary to well differentiated carcinomas. Specimens with cyclin D1 overexpression showed a high incidence of lymph permeation, venous permeation, and lymph node metastasis. We conclude that nuclear cyclin D1 overexpression is a critical event importantly associated with cell proliferation and invasive growth in gallbladder carcinogenesis, and that cyclin D1 immunostaining may become a useful marker for evaluating gallbladder carcinomas. Received: March 9, 1999 / Accepted: July 23, 1999 |
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Keywords: | : gallbladder cancer cyclin D1 p53 K-ras Ki-67 |
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