Genetic counseling is common place in the world of breast cancer including the evaluation of the BRCA genes. Prostate and breast cancer increasingly been shown to have a relationship, perhaps all the down to the genetic level.
Researchers are now understanding, that like in breast cancer, BRCA1 loss preexisting in small sub-populations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood vesicles.
At the Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances among circulating tumor cells (CTC). The researchers performed an analysis aimed to elucidate the biological and clinical roles of BRCA1 losses in metastatic spread and tumor progression in men with prostate cancer.
They mapped the molecular progression in prostate cancer outgrowth, by using fluorescence in situ hybridization analysis of primary tumors and lymph node sections, and CTCs from peripheral blood.
They found that:
• 14% of 133 tested men carried monoallelic BRCA1 loss in at least one tumor focus.
• Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by allelic imbalance of the tumor suppressor gene PTEN and lack of BRCA1 promoter methylation.
• The BRCA1 losses correlated with advanced T stage (P < 0.05), invasion to pelvic lymph nodes (P < 0.05), as well as biochemical recurrence (P < 0.01).• Their prevalence was twice as high within 62 lymph node metastases (LNM) as in primary tumors (27%, P < 0.01).• The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between these two sites.• In four of seven men with metastatic disease, BRCA1 losses appeared in a minute fraction of cytokeratin- and vimentin-positive CTCs.So, what does all this mean? Simply, there is evidence that a BRCA1 loss might initiate tumor spread as well as provide an early indicator of shortened disease-free survival within a small subpopulation of prostate cancer cells.
Clin Cancer Res. 2010 Jul 1;16(13):3340-8.
doi: 10.1158/1078-0432.CCR-10-0150 ; Bednarz N, Eltze E, Semjonow A, Rink M, Andreas A, Mulder L, Hannemann J, Fisch M, Pantel K, Weier HU, Bielawski KP, Brandt B.
Joel T Nowak, M.A., M.S.W.