title: Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis.
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.
authors.affiliation: Fourth Department of Internal Medicine, Tokyo Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Itoi
authors.forename: Y
authors.initials: Y
authors.lastname: Shinohara
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Takei
authors.forename: J
authors.initials: J
authors.lastname: Sanada
authors.forename: T
authors.initials: T
authors.lastname: Horibe
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Kasuya
authors.forename: Y
authors.initials: Y
authors.lastname: Ebihara
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism*; D003062:Codon; D019938:Cyclin D1 / Q000096:biosynthesis*; D004273:DNA, Neoplasm / Q000032:analysis; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1