Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive urothelial cancer: a multivariate survival study including proliferation markers and cell cycle regulators
| Autor: | Hariklia Gakiopoulou, Angelica A. Saetta, Irene Thymara, Euphemia Thomas-Tsagli, Athina Goudopoulou, Penelope Korkolopoulou, N. Givalos, Efstratios Patsouris |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Pathology medicine.medical_specialty Proliferation index Cell Cycle Proteins Biology Pathology and Forensic Medicine Biomarkers Tumor medicine Carcinoma Humans Survival rate Survival analysis Aged Retrospective Studies Aged 80 and over Carcinoma Transitional Cell Muscle Neoplasms Bladder cancer Cell growth Tumor Suppressor Proteins Middle Aged Cell cycle Prognosis medicine.disease Immunohistochemistry Survival Analysis DNA-Binding Proteins Survival Rate Ki-67 Antigen Urinary Bladder Neoplasms Cancer research Female Schizosaccharomyces pombe Proteins Tumor Suppressor Protein p53 Urothelium Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Human Pathology. 36:899-907 |
| ISSN: | 0046-8177 |
| DOI: | 10.1016/j.humpath.2005.06.008 |
| Popis: | Evaluation of cell cycle regulators has gained special interest in the effort to increase the amount of prognostic information in malignant tumors. Minichromosome maintenance proteins (MCMs) drive the formation of prereplicative complexes, which is the first key event during G1 phase. Therefore, altered MCM expression may be a hallmark of cell cycle deregulation, which is supposed to be the most essential mechanism in the development and progression of bladder cancer. Our aim was to investigate the value of MCMs as proliferation markers and prognostic indicators in detrusor muscle-invasive urothelial bladder carcinomas. We analyzed immunohistochemically the expression of MCM-2 and MCM-5 in 65 patients with detrusor muscle-invasive urothelial bladder carcinomas in relation with clinicopathologic parameters, patients' overall and disease-free survival, and the expression of the conventional proliferation index Ki-67 and other cell cycle modulators (p53, pRb, p21(WAF1), and p27(Kip1)). The levels of MCM-2 and MCM-5 were significantly higher in high-grade (P < .0001), advanced-stage (P = .001), and nonpapillary tumors (P < .0001). The expression of MCM-2 and MCM-5 significantly associated with the conventional proliferation index Ki-67 (P = .0001 for each protein). The expression of MCM-2 or MCM-5 positively correlated with p53 labeling index (P = .014 and P = .009, respectively). Also, median p21(WAF1) labeling index was higher in MCM-5 high expressors (P = .028). Finally, both MCM-2 and MCM-5 associated significantly with adverse patients' outcome in both univariate (P = .0072 and P = .0074, respectively) and multivariate (P = .0001) analysis. In conclusion, MCM-2 and MCM-5 appear to be reliable proliferation indexes and useful prognostic markers in patients with muscle-invasive urothelial bladder carcinomas. |
| Databáze: | OpenAIRE |
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