Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

• Published in: Clinical cancer research 2010-01, Vol.16 (1), p.56-64
• Main Authors: EL GAMMAL, Alexander T, BRÜCHMANN, Michael, BOKEMEYER, Carsten, BRÜMMENDORF, Tim H, IZBICKI, Jakob R, YEKEBAS, Emre, FISCH, Margit, HULAND, Hartwig, GRAEFEN, Markus, SCHLOMM, Thorsten, ZUSTIN, Jozef, ISBARN, Hendrik, HELLWINKEL, Olaf J. C, KÖLLERMANN, Jens, SAUTER, Guido, SIMON, Ronald, WILCZAK, Waldemar, SCHWARZ, Jörg
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Chromosome; Chromosome Aberrations; Chromosome Deletion; Chromosomes, Human, Pair 8; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization, Fluorescence; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prognosis; Prostate Cancer; Prostate-Specific Antigen; Prostatic Neoplasms - genetics; Tissue Array Analysis; Tissue Microarray; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-1423

Purpose: Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown. Experimental Design: To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization. Results : Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/ 8q gains were found in 26.1%/4.8% of 1,239 pT 2 cancers, 38.5%/9.8% of 379 pT 3a cancers, 43.5%/8.9% of 237 pT 3b cancers, 40.7%/14.8% of 27 pT 4 cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers ( P < 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other ( P < 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain ( P < 0.0001). Among cancers treated with radical prostatectomy, 8p deletions ( P = 0.003) and 8q gains ( P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence. Conclusions : 8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application. Clin Cancer Res; 16(1); 56–64