PMID- 15122326 OWN - NLM STAT- MEDLINE DCOM- 20040805 LR - 20061115 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 23 IP - 33 DP - 2004 Jul 22 TI - E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. PG - 5616-23 AB - E2F3 is located in the 6p22 bladder amplicon and encodes a transcription factor important for cell cycle regulation and DNA replication. To further investigate the role of E2F3 in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for gene copy number and expression analysis by means of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). E2F3 amplification was strongly associated with invasive tumor phenotype and high tumor grade (P < 0.0001 each). None of 272 pTaG1/G2 tumors, but 35 of 311 pT1-4 carcinomas (11.3%), had E2F3 amplification. A high E2F3 expression level was associated with high grade, advanced stage, and E2F3 gene amplification (P < 0.0001 each). To evaluate whether E2F3 expression correlates with tumor proliferation, the Ki67 labeling index (LI) was analysed for each tumor. There was a strong association between a high Ki67 LI and E2F3 expression (P < 0.0001), which was independent of grade and stage. We conclude that E2F3 is frequently amplified and overexpressed in invasively growing bladder cancer (stage pT1-4). E2F3 expression appears to provide a growth advantage to tumor cells by activating cell proliferation in a subset of bladder tumors. CI - Copyright 2004 Nature Publishing Group FAU - Oeggerli, Martin AU - Oeggerli M AD - Institute of Pathology, Schoenbeinstrasse 40, CH-4031 Basel, Switzerland. FAU - Tomovska, Sanja AU - Tomovska S FAU - Schraml, Peter AU - Schraml P FAU - Calvano-Forte, Daniele AU - Calvano-Forte D FAU - Schafroth, Salome AU - Schafroth S FAU - Simon, Ronald AU - Simon R FAU - Gasser, Thomas AU - Gasser T FAU - Mihatsch, Michael J AU - Mihatsch MJ FAU - Sauter, Guido AU - Sauter G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (E2F3 Transcription Factor) RN - 0 (E2F3 protein, human) RN - 0 (Ki-67 Antigen) RN - 0 (Transcription Factors) SB - IM MH - Cell Division MH - E2F3 Transcription Factor MH - *Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Ki-67 Antigen/metabolism MH - Prognosis MH - Protein Array Analysis MH - Transcription Factors/*genetics/metabolism MH - Urinary Bladder Neoplasms/*genetics EDAT- 2004/05/04 05:00 MHDA- 2004/08/06 05:00 CRDT- 2004/05/04 05:00 PHST- 2004/05/04 05:00 [pubmed] PHST- 2004/08/06 05:00 [medline] PHST- 2004/05/04 05:00 [entrez] AID - 1207749 [pii] AID - 10.1038/sj.onc.1207749 [doi] PST - ppublish SO - Oncogene. 2004 Jul 22;23(33):5616-23. doi: 10.1038/sj.onc.1207749.