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(American Journal of Pathology. 2001;159:2089-2094.)
© 2001 American Society for Investigative Pathology

Regular Article

Amplification of EIF3S3 Gene Is Associated with Advanced Stage in Prostate Cancer

Outi Saramäki^*, Niels Willi, Ola Bratt, Thomas C. Gasser, Pasi Koivisto^¶, Nina N. Nupponen^||, Lukas Bubendorf and Tapio Visakorpi^*

From the Laboratory of Cancer Genetics,^*
Institute of Medical Technology, and the Department of Clinical Genetics and Laboratory of Cancer Genetics,^¶
Tampere University Hospital, Tampere, Finland; the Institute for Pathology
and Urologic Clinics BS/BL,
University of Basel, Basel, Switzerland; the Department of Surgery,
Helsingborg Hospital, Helsingborg, Sweden; and the Cancer Genetics Branch,^||
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland

Gain of the long arm of chromosome 8 (8q) is one of the most common gains found in the advanced prostate cancer by comparative genomic hybridization. We have previously identified a putative target gene for the 8q gain, EIF3S3, that encodes a p40 subunit of eukaryotic translation initiation factor 3 (eIF3). Here, we studied the frequency of the EIF3S3 amplification in different stages of prostate cancer and co-amplification of EIF3S3 and oncogene MYC. In addition, prognostic utility of the EIF3S3 copy number alteration was evaluated. The analyses were done with fluorescence in situ hybridization and tissue microarray technology. High-level amplification of EIF3S3 was found in 11 of 125 (9%) of pT1/pT2 tumors, 12 of 44 (27%) of pT3/pT4 tumors, and 8 of 37 (22%) of lymph node metastases as well as in 26 of 78 (33%) and 15 of 30 (50%) of hormone refractory locally recurrent tumors and metastases, respectively. The amplification was associated with high Gleason score (P < 0.001). One of the 79 tumors with EIF3S3 amplification had only two copies of MYC, whereas all tumors with amplification of MYC had also amplification of EIF3S3 indicating common co-amplification of the genes. Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas (P = 0.023). In the analyses of prostatectomy-treated patients, the amplification was not statistically significantly associated with progression-free time. In conclusion, amplification of EIF3S3 gene is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease.

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