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(American Journal of Pathology. 2004;165:63-69.)
© 2004 American Society for Investigative Pathology

TRIO Amplification and Abundant mRNA Expression Is Associated with Invasive Tumor Growth and Rapid Tumor Cell Proliferation in Urinary Bladder Cancer

Min Zheng*, Ronald Simon*, Martina Mirlacher*, Robert Maurer{dagger}, Thomas Gasser{ddagger}, Thomas Forster{ddagger}, Pierre Andre Diener§, Michael J. Mihatsch*, Guido Sauter* and Peter Schraml*

From the Institute of Pathology,* University of Basel, Basel; the Institute of Pathology,{dagger} City Hospital Triemli, Zürich; the Urologic Clinics,{ddagger} Cantonal Hospital Liestal, Liestal; and the Institute of Pathology,§ Cantonal Hospital St. Gallen, St. Gallen, Switzerland

Studies by comparative genome hybridization have suggested that 5p amplification is related to tumor progression in urinary bladder cancer. In this study seven genes (TAS2R, ADCY2, DNAH5, CTNND2, TRIO, ANKH, and MYO10) located to 5p15.31-5p15.1 were analyzed by fluorescence in situ hybridization using a tissue microarray containing samples from tumors and cell lines with known 5p amplification by comparative genome hybridization. Amplification frequency was highest for TRIO, which maps to 5p15.2 and encodes a protein with a putative role in cell-cycle regulation. To further investigate the role of TRIO amplification in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for fluorescence in situ hybridization analysis. TRIO amplification was strongly associated with invasive tumor phenotype, high tumor grade, and rapid tumor cell proliferation (Ki67 LI) (P < 0.0001 each). Only 7 of 456 pTaG1/G2 tumors (1.5%) but 62 of 485 pT1-4 carcinomas (12.8%) had TRIO amplification. TRIO amplification was not associated with poor prognosis. Using a frozen bladder tumor tissue microarray RNA in situ hybridization confirmed that TRIO is up-regulated in amplified tumors. It is concluded that TRIO up-regulation through amplification has a potential role in bladder cancer progression.




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