Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis.
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.
Itoi
T
T
Fourth Department of Internal Medicine, Tokyo Medical University, Japan.
Shinohara
Y
Y
Takeda
K
K
Nakamura
K
K
Takei
K
K
Sanada
J
J
Horibe
T
T
Saito
T
T
Kasuya
K
K
Ebihara
Y
Y
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
D014408:Biomarkers, Tumor; D003062:Codon; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1