Expression and clinical significance of the G1-S modulators in intrahepatic cholangiocellular carcinoma

Oncology. 2001;60(3):242-51. doi: 10.1159/000055325.


Objective: To elucidate the clinical roles of G1-S modulators in cholangiocellular carcinoma (CCC).

Methods: We performed immunohistochemistry using antibodies against the retinoblastoma gene product (pRb), p16, p21, p27, p53 and cyclin D1 for 41 cases of CCC as well as normal bile ducts.

Results: The p27 labeling index (LI) was significantly higher in cases without lymph node metastasis than in normal bile ducts, but it decreased greatly in cases with lymph node metastasis. It was inversely related to the Ki-67 LI. The p16 LI also showed a relationship with lymph node metastasis, but not with the Ki-67 LI. The p21 LI was even higher in poorly differentiated cases and showed a direct relationship with the Ki-67 LI, although it is a negative regulator of the cell cycle. pRb expression did not correlate with any clinicopathological features. Cyclin D1 overexpression was more frequently observed in cases with poor or moderate differentiation and with lymph node metastasis. Cyclin D1 overexpression and aberrant p53 expression showed direct relationships with the Ki-67 LI.

Conclusions: These results suggest that in CCC: (1) p27 expression reflects the biological character of the carcinoma and may regulate its progression; (2) cyclin D1 plays a crucial role in cell cycle progression, and (3) aberrant p53 expression has some effect on CCC cell proliferating activity.

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / pathology*
  • Bile Ducts, Intrahepatic*
  • Cholangiocarcinoma / pathology*
  • Cyclin D1 / analysis
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / analysis
  • Female
  • G1 Phase*
  • Genes, p16
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Retinoblastoma Protein / analysis
  • S Phase*
  • Tumor Suppressor Protein p53 / analysis


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Cyclin D1