A new diagnostic tool for prostate cancer and how a bigger chromosome 8 can predict poorer outcomes in prostate cancer patients

The problem is that the current methods of disease testing are still associated with too many misdiagnoses. Now however, research by Portuguese and Norwegian scientists, just published on the journal Clinical Cancer Research describes, not only how whole genome analysis can help to increase the accuracy of patient testing, but also identifies a new molecular marker that “tags” prostate cancers with worse prognoses These results have important implications for the clinical management of patients as they will allow, together with standard methods of cancer analysis, better informed therapeutic measures.

Prostate cancer results from abnormal uncontrolled growth of cells in the prostate, which is a doughnut-shaped gland in the male reproductive system responsible for the fluid that carries the sperm during ejaculation. The disease is strongly related to the Western lifestyle and affects mostly males over the age of 65, while rarely occurring before 40 years of age.

Initial diagnosis is done by measuring prostate-specific antigen (PSA), a protein produced by the healthy male prostate, but also by cancer cells. When high levels of PSA are detected, indicating an increased likelihood of cancer, a prostate biopsy is done. The sample collected in this way is analysed by microscope, and, if a carcinoma is detected, radical prostatectomy (removal of the prostate) and radiotherapy follows. The problem is that biopsy samples are very small and, in consequence, it is difficult not only to know how representative of the tumour are the cells tested, but also to determine accurately the tumour’s stage (degree of advancement of the disease) and grade (tumour’s malignancy and aggressiveness)

And in fact, studies looking at diagnoses obtained from biopsies samples, and comparing these with those obtained later from the same prostates after surgery, concluded that biopsies analyses tended to downgrade about 57% of tumours, while overgrading a significant 20% of them. This, together with the fact that PSA testing can give a positive result to slow-growing tumours that probably will never create problems, further raises the problem of misdiagnoses in prostate cancer and the need to improve testing methods.

Franclim R. Ribeiro, Manuel R.Teixeira and colleagues from Portugal and Norway, have previously found that it was possible, from biopsies samples, to do a full genome analysis which, in combination with the microscopic analyses, should allow a much more accurate tumour classification

In the research now published, the group of scientists show the possibilities of this new method by studying 61 patients with high levels of PSA and microscopic evidence of prostate cancer, to find that the total number of genomic aberrations found in these patient’s prostate cells is directly associated with cancer severity (higher number of aberrations – increased disease severity). A number of healthy individuals were also analysed and shown to have no genomic changes in their prostate cells, confirming the specificity of the patients’ findings.

Furthermore, Ribeiro, Teixeira and colleagues found that the gain of chromosomal material within the long arm of chromosome 8 (all human chromosomes have 2 arms, one shorter and one longer) was an accurate predictor of poor survival in prostate cancer patients. This was true even when patients were aggregated according to the tumour grade and disease stage, as in the case of patients with tumours with Gleason score 7 (Gleason grading system goes from 2 to 10, with 10 being tumours with the worst prognosis). This is especially interesting as grade 7 tumours are known, not only by being very aggressive but also by being difficult to evaluate in terms of prognostic.

Teixeira and colleagues believe that the use of genomic analysis, together with the more standard methods now employed, can help to achieve better diagnoses by detecting more effectively both aggressive and less aggressive carcinomas. In the later case, correct diagnosis would allow doctors to chose to close monitoring the tumours, instead of rush into radical prostatectomy with its inherent psychological and health problems.

Piece researched and written by: Catarina Amorim (catarina.amorim@linacre.ox.ac.uk)