title: Expression and clinical significance of the G1-S modulators in carcinoma of the extrahepatic bile duct.
abstract: Expression of cell cycle modulators at the G1-S boundary, the retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D1 as well as Ki-67 was investigated with 39 extrahepatic bile duct carcinomas (BDC). The Ki-67 labeling index (LI) was higher in cases with poor differentiation, lymph node metastasis and stage III or IV. Cyclin D1 overexpression was seen in 14 cases (35.8%). This phenomenon could be observed more frequently in cases of hilar carcinoma and with poor differentiation, perineural invasion, lymphatic invasion and lymph node metastasis. Furthermore, Ki-67 LI was higher in cyclin D1 overexpressing cases. p27 expression showed inverse relationships with Ki-67 LI, lymph node metastasis and aberrant p53 expression. Although p16 and p21 expression significantly correlated with lymph node metastasis and cyclin D1 overexpression, respectively, they were not related to Ki-67 LI. pRb expression was observed in all cases. Although the LI was lower in carcinoma of upper and middle bile ducts, no correlation was established between pRb expression and other clinicopathological parameters including Ki-67 LI. Aberrant p53 expression was observed in 13 cases (33.3%) and Ki-67 LI was significantly higher in these cases. These findings suggest that p27 and cyclin D1 strongly correlate with BDC proliferation and reflect the biological aggressiveness of this carcinoma.
authors.affiliation: Department of Surgery, Osaka Seamen's Insurance Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Sakon
authors.forename: M
authors.initials: M
authors.lastname: Monden
authors.forename: M
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: N
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000737:chemistry* / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division; D019938:Cyclin D1 / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D005260:Female; D016193:G1 Phase / Q000502:physiology*; D005786:Gene Expression Regulation; D016161:Genes, Retinoblastoma; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D016160:Retinoblastoma Protein / Q000032:analysis; D016196:S Phase / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27