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Genitourinary cancer Joaquim Bellmunt

Prostate cancer is the most common male malignancy but its progression rate is only 30%. In autopsy series, it has been shown that it may be present in a greater percentage than usually estimated, from the 4th decade. More refined detection methods are increasing the number of patients undergoing radical surgical treatment for tumors that perhaps would not progress.

Due to the difficulties in obtaining samples for high throughput molecular analysis from early tumors, genes that could be decisive for the transition from a latent phase to an aggressive one leading to progression, are still unknown. Therefore, there are no clues to select patients for a less radical treatment. If genes distinguishing these groups were identified, a better knowledge of the natural history of prostate cancer could be gained, and it could be applied to better identifying patient risk and to designing more precise therapeutic strategies.

Objectives

To identify genetic signatures that could be involved in the transition from a hypothetical latent to a clinically significant phase, to better understand the natural history of prostatic carcinoma and to design adequate treatment strategies for each patient.

Methodology

• Tumor subgroups: 
  • clinically significant 
  • autopsy (latent) 
  • cystoprostatectomy (incidental)
  • “insignificant” (<0,5 cc, pT2 or lower, Gleason grade=6, no pattern 4) 
  • metastatic (advanced) 
• Study of genetic expression profiles in each group. A new assay to obtain RNA for high throughput studies from paraffin-embedded tissue will be used in combination with CGH arrays and RNA expression arrays in fresh samples obtained with a refined grossing technique. 
• Molecular study of selected genes (TP53, KLF6, FGFR3, PTEN, c-MYC, k-RAS, EGFR, HER-2-neu, AMACR, GSTP1, ATBF1). Manual or laser microdissection, and RT-PCR, PCR and direct sequencing are being performed. Depending on results, loss of heterocygosity (LOH, FISH) or methylation analysis, and immunohistochemistry of selected proteins will be performed.