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Expression of G1-S modulators (p53, p16, p27, cyclin D1, Rb) and Smad4/Dpc4 in intrahepatic cholangiocarcinoma
- Source :
- Human pathology. 33(9)
- Publication Year :
- 2002
-
Abstract
- Aberrations of G1-S cell cycle arrest and TGF-beta/Smad pathway are critical events in human carcinogenesis. We studied alterations of both pathways by immunohistochemical staining for p53, p16, p27, cyclin D1, Rb and Smad4/Dpc4 in 42 intrahepatic cholangiocarcinomas (ICCs). Abnormal nuclear overexpression of p53 and cyclin D1 was noted in 15 (35.7%) and 26 (61.9%) cases, respectively. Total loss of p16, p27, Rb and Smad4 was detected in 15 (35.7%), 13 (31.0%), 5 (11.9%) and 19 (45.2%) cases, respectively. Forty cases (95.2%) showed aberrations of at least one of the pathways, of which 21 (50%) revealed abnormality in G1-S pathway only, 17 (40.5%) had abnormalities in both pathways and 2 (4.8%) had an abnormality in TGF-beta/Smad pathway only. Among the examined genes, loss of Smad4 was found to have a positive relationship with the pTNM stage (P < 0.05). The overall stage of the high-altered group (alterations in 2 to 5 of the genes, n = 29) was significantly higher than that of the low-altered group (alteration of one or no gene, n = 13) (P < 0.01). We also examined the expression of above genes in the accompanying biliary dysplasia and found out abnormal expression of p53, cyclin D1 or p16 in 7 out of 13 dysplastic lesions. Our data suggest that abnormal G1-S cell cycle and altered TGF-beta/Smad pathway are major events in cholangiocarcinogenesis. Moreover, there might be a possible cumulative effect of the alterations in the examined genes upon the clinical outcome of patients with resectable ICCs.
- Subjects :
- Adult
Male
Tumor suppressor gene
Muscle Proteins
Cell Cycle Proteins
SMAD
medicine.disease_cause
Retinoblastoma Protein
Pathology and Forensic Medicine
Cholangiocarcinoma
Immunoenzyme Techniques
Cyclin D1
Cyclin-dependent kinase
medicine
Biomarkers, Tumor
Humans
Genes, Tumor Suppressor
Intrahepatic Cholangiocarcinoma
Cyclin-Dependent Kinase Inhibitor p16
Aged
Neoplasm Staging
Smad4 Protein
Cell Nucleus
biology
Microfilament Proteins
Retinoblastoma protein
Cell cycle
Middle Aged
Neoplasm Proteins
DNA-Binding Proteins
Bile Ducts, Intrahepatic
Bile Duct Neoplasms
biology.protein
Cancer research
Trans-Activators
Female
Tumor Suppressor Protein p53
Carcinogenesis
Subjects
Details
- ISSN :
- 00468177
- Volume :
- 33
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Human pathology
- Accession number :
- edsair.doi.dedup.....989c9c438cf5aa59bdbb39418fabe6cf