Prostate Cancer

Prostate cancer is the second most common cancer among men. Several genetic abnormalities have been identified and correlated with prognosis.

 

FISH Assays:

PTEN (10q23): PTEN deletion is associated with tumor progression and predictive of shorter time to recurrence.1 Additional studies have identified three patient groups based on the ERG and PTEN biomarkers: (1) ‘poor genomic grade’ characterized by both PTEN deletion and TMPRSS2:ERG fusions; (2) ‘intermediate genomic grade’ with either PTEN deletion or TMPRSS2:ERG fusion, and (3) ‘favorable genomic grade’ in which neither rearrangement was present.2

ERG-BA (21q22): ERG over expression is an early event in prostate oncogenesis. Researchers have shown that TMPRSS2:ERG fusion (Edel) in conjunction with a copy number increase (2+Edel) is associated with poor disease specific survival in men undergoing initial active surveillance in localized prostate cancer, as well as a high likelihood for biochemical recurrence in men undergoing radical prostatectomy.3 Others have shown that ERG gene polysomy was significantly associated with recurrence.4 Additional studies have identified three patient groups based on the ERG and PTEN biomarkers (See PTEN above).2

MYC (8q24 ): MYC amplification has been shown to contribute to disease initiation, progression, and is a key precursor to invasive prostatic adenocarcinoma.5

CTNND2 (5p15): CTNND2 is significantly overexpressed in prostate cancer compared to benign prostate hyperplasia (BPH) and thus is a potential candidate for the diagnosis and management of prostate cancer.6

 
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References

  1. Yoshimoto M, Cunha IW, Coudry RA, Fonseca FP, Torres CH, Soares FA, Squire JA. FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer. 2007 Sep 3;97(5):678-85. Epub 2007 Aug 14. PubMed PMID: 17700571; PubMed Central PMCID: PMC2360375.
  2. Yoshimoto M, Joshua AM, Cunha IW, Coudry RA, Fonseca FP, Ludkovski O, Zielenska M, Soares FA, Squire JA. Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod Pathol. 2008 Dec;21(12):1451-60. doi: 10.1038/modpathol.2008.96. Epub 2008 May 23. PubMed PMID: 18500259.
  3. Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, Berney D, Foster CS, Fletcher A, Gerald WL, Moller H, Reuter V, De Bono JS, Scardino P, Cuzick J, Cooper CS; Transatlantic Prostate Group. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene. 2008 Jan 10;27(3):253-63. Epub 2007 Jul 16. PubMed PMID: 17637754; PubMed Central PMCID: PMC2646890.
  4. Toubaji A, Albadine R, Meeker AK, Isaacs WB, Lotan T, Haffner MC, Chaux A,Epstein JI, Han M, Walsh PC, Partin AW, De Marzo AM, Platz EA, Netto GJ.Increased gene copy number of ERG on chromosome 21 but not TMPRSS2-ERG fusionpredicts outcome in prostatic adenocarcinomas. Mod Pathol. 2011Nov;24(11):1511-20. doi: 10.1038/modpathol.2011.111. Epub 2011 Jul 8. PubMed PMID: 21743434; PubMed Central PMCID: PMC3360950.
  5. MYC and Prostate Cancer. Koh CM, Bieberich CJ, Dang CV, Nelson WG, Yegnasubramanian S, De Marzo AM. Genes Cancer. 2010 Jun;1(6):617-28.
  6. Burger MJ, Tebay MA, Keith PA, Samaratunga HM, Clements J, Lavin MF, Gardiner RA. Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer. Int J Cancer. 2002 Jul 10;100(2):228-37. PubMed PMID: 12115574.