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Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome.
Int J Cancer. 2002 Feb 10; 97(5):671-8.IJ

Abstract

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.

Authors+Show Affiliations

Centro di Ricerche Oncologiche "Giovanni XXIII," Istituto di Patologia Generale, Catholic University, Rome, Italy. asgambato@rm.unicatt.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11807796

Citation

Sgambato, Alessandro, et al. "Cyclin D1 Expression in Papillary Superficial Bladder Cancer: Its Association With Other Cell Cycle-associated Proteins, Cell Proliferation and Clinical Outcome." International Journal of Cancer, vol. 97, no. 5, 2002, pp. 671-8.
Sgambato A, Migaldi M, Faraglia B, et al. Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. Int J Cancer. 2002;97(5):671-8.
Sgambato, A., Migaldi, M., Faraglia, B., De Aloysio, G., Ferrari, P., Ardito, R., De Gaetani, C., Capelli, G., Cittadini, A., & Trentini, G. P. (2002). Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. International Journal of Cancer, 97(5), 671-8.
Sgambato A, et al. Cyclin D1 Expression in Papillary Superficial Bladder Cancer: Its Association With Other Cell Cycle-associated Proteins, Cell Proliferation and Clinical Outcome. Int J Cancer. 2002 Feb 10;97(5):671-8. PubMed PMID: 11807796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome. AU - Sgambato,Alessandro, AU - Migaldi,Mario, AU - Faraglia,Beatrice, AU - De Aloysio,Graziella, AU - Ferrari,Paolo, AU - Ardito,Raffaele, AU - De Gaetani,Carmela, AU - Capelli,Giovanni, AU - Cittadini,Achille, AU - Trentini,Gian Paolo, PY - 2002/1/25/pubmed PY - 2002/2/9/medline PY - 2002/1/25/entrez SP - 671 EP - 8 JF - International journal of cancer JO - Int. J. Cancer VL - 97 IS - 5 N2 - Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer. SN - 0020-7136 UR - https://www.unboundmedicine.com/medline/citation/11807796/Cyclin_D1_expression_in_papillary_superficial_bladder_cancer:_its_association_with_other_cell_cycle_associated_proteins_cell_proliferation_and_clinical_outcome_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0020-7136&amp;date=2002&amp;volume=97&amp;issue=5&amp;spage=671 DB - PRIME DP - Unbound Medicine ER -