High Nuclear Cyclin D1 Expression in Lymph Node Metastases from Bladder Cancer Is an Independent Risk Factor for Early Death.
Achim Fleischmann, Diana Rotzer, George N Thalmann, Roland Seiler. University of Bern, Switzerland
Background: CyclinD1 not only promotes proliferation but also mediates invasion and metastasis of cancer cells thus contributing to a malignant phenotype. With increased understanding of its diverse functions CyclinD1 has been suggested to be interesting therapeutic target in cancer. The prognostic impact of CyclinD1 expression in lymph node positive bladder cancer has never been determined.
Design: One hundred and fifty lymph node positive patients with urothelial bladder cancer underwent cystectomy and pelvic lymphadenectomy and were followed prospectively for a median of 7.1 years (range 0.1-19.9). A tissue microarray was constructed with samples from all primary tumors and matched lymph node metastases. Immunohistochemical stains showed CyclinD1 expression in the nucleus and the cytoplasm. In each patient, percentage of stained cancer cells was determined in the primary tumor and the metastases considering the sub-cellular expression compartment. Expression data were correlated with tumor characteristics and survival.
Results: Nuclear and cytoplasmic CyclinD1expression were significantly (p<0.05) up-regulated in metastases (median nuclear/cytoplasmic expression: 50%/15%) compared to primary tumors (median nuclear/cytoplasmic expression: 30%/0%). High nuclear CyclinD1 expression in the metastases predicted early death significantly (p=0.003; 5-year overall survival: 14% vs. 37%) and independent from other risk factors (TNM stages, extranodal extension). These patients had a 1.7 fold elevated risk of dying compared to patients with low CyclinD1 expression (p=0.017). CyclinD1 expression in all other tumor cell compartments failed to add significant prognostic information and CyclinD1 expression was not correlated with specific tumor characteristics (TNM stage; number, total diameter and extracapsular extension of metastases).
Conclusions: Nuclear CyclinD1 expression in nodal metastases of bladder cancer is significantly up-regulated and predicts early death independently. This may help to identify high-risk patients and personalize adjuvant therapies, thus improving patient management.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 186, Tuesday Morning