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Alterations of cell cycle regulators in localized synovial sarcoma: A multifactorial study with prognostic
C R Antonescu1, D H Leung, M Dudas
1Department of Pathology, Human Genetics, and Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
The American Journal of Pathology
|March 7, 2000
Summary
Genetic alterations in cell cycle regulators are more common in synovial sarcoma (SS) than previously believed. p53 overexpression and high Ki67 proliferation predict increased relapse risk in SS patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Recurrent chromosomal translocations are common in sarcomas.
- Genetic alterations in cell cycle regulators were thought to be secondary events in sarcomas.
Purpose of the Study:
- To investigate the frequency and clinical implications of cell cycle regulator alterations in synovial sarcoma (SS).
- To assess the prognostic value of specific cell cycle proteins and Ki67 in localized SS.
Main Methods:
- Analyzed 49 localized SS patient samples for G1 checkpoint and G1-S transition proteins (cyclins D1, E, p21, p27, mdm2, p53) and Ki67.
- Utilized immunohistochemistry with defined positive phenotype cutoffs.
- Correlated protein expression with disease-specific survival using Kaplan-Meier and Cox regression.
Main Results:
- Positive phenotypes observed: cyclin D1 (59%), cyclin E (29%), p21 (51%), p27 (69%), mdm2 (59%), p53 (16%), Ki67 (59%).
- p53, cyclin E, and high Ki67 correlated with survival.
- p53 and Ki67 were independent prognostic variables.
Conclusions:
- Cell cycle regulator alterations are frequent in SS.
- p53 overexpression and high Ki67 index can identify SS patients at higher risk of relapse.
- These markers may aid in risk stratification for SS.