Clinical Services

Prostate BioStrat® Assay

Prostate Cancer - Background

Prostate cancer is a complex heterogeneous disease and can have strikingly different clinical behaviors and responses to therapy. Accurate prognostication is a prerequisite for accurate therapeutics and management of prostate cancer because indolent tumors may require no intervention, whereas aggressive tumors lead to patient mortality.

There is a critical need to define these subgroups of patients with prostate cancer differing in clinical outcome. Previous efforts to predict extent of disease and natural history of prostate cancer have focused on Gleason score of the needle biopsy sample, serum prostate-specific antigen (PSA) concentration, and clinical stage.1 Published nomograms based on these three parameters provide useful predictions of clinical states and outcomes,2,3 but they need further refinements to improve accuracy and universality. More accurate prognostic markers for this patient group would permit assignment of more aggressive treatment to those most likely to fail and would justify expectant management (deferral of active treatment) in those likely to have indolent disease.

Introduction to Prostate BioStrat® Assay

The Prostate BioStrat® Assay utilizes one or more fluorescence in situ hybridization (FISH) assays specifically selected to help detect, accurately diagnose and assess the severity of prostate cancer at the time of biopsy. Assays can be performed on both formalin-fixed paraffin-embedded (FFPE) biopsy and fine needle aspiration (FNA) samples. Results from the assays can be used to assist cancer detection, confirm diagnosis and as an aid to distinguish patients with indolent disease from those with clinically relevant cancers thereby allowing for either conservative management (active surveillance and deferred intervention) or more aggressive primary and/or neoadjuvant or adjuvant treatment.

Prostate BioStrat® Assay FISH Probe Sets
PTEN
RESULTS IMAGE HYBRIDIZATION PATTERN CLINICAL CORRELATION
Normal Normal result observed in a prostate cell after hybridization with the PTEN (10q22) and Chromosome 10 (CEP10) FISH probe showing two PTEN (red) and two Chromosome 10 (green) signals. Detection/Confirmation: Supports benign and/or low risk histological findings.
Cancer Stratification: May predict favorable prostate cancer risk.
Abnormal
(Hemizygous Deletion)
Abnormal result observed in a prostate cell after hybridization with the PTEN (10q22) and Chromosome 10 (CEP10) FISH probe showing one PTEN (red) and two Chromosome 10 (green) signals. Detection/Confirmation: May predict active and/or potential prostate adenocarcinoma.
Cancer Stratification: May predict unfavorable prostate cancer risk. May predict unfavorable prostate cancer risk.
TMPRSS2-ERG
RESULTS IMAGE HYBRIDIZATION PATTERN CLINICAL CORRELATION
Normal Normal result observed in a prostate cell after hybridization with the TMPRSS2-ERG (21q22) rearrangement FISH probe showing two (red/green/blue) fusion signals. Detection/Confirmation: Supports benign and/or low risk histological findings.
Cancer Stratification: May predict favorable prostate cancer risk.
Abnormal
(TMPRSS2-ERG fusion via deletion)
Abnormal result observed in a prostate cell after hybridization with the TMPRSS2-ERG (21q22) rearrangement FISH probe showing one (red/blue) and one (red/green/blue) fusion signals. Detection/Confirmation: May predict active and/or potential prostate adenocarcinoma.
Cancer Stratification: May predict unfavorable prostate cancer risk.
CHROMOSOME 8, C-MYC AND LPL
RESULTS IMAGE HYBRIDIZATION PATTERN CLINICAL CORRELATION
Normal Normal result observed in a prostate cell after hybridization with the Chromosome 8 (CEP8), LPL (8p22) and C-MYC (8q24) FISH probe showing two Chromosome 8 (aqua), two LPL (orange) and two C-MYC (green) signals. Cancer Stratification: May predict favorable prostate cancer risk.
Abnormal
(Loss LPL, gain chromosome 8 and amplification C-MYC)
Abnormal result observed in a prostate cell after hybridization with the Chromosome 8 (CEP8), LPL (8p22) and C-MYC (8q24) FISH probe showing three Chromosome 8 (aqua), five C-MYC (green) and one LPL (orange) signals. Cancer Stratification: May predict unfavorable prostate cancer risk.

Prostate BioStrat® for Detecting and Confirming Prostate Cancer

False Negative Biopsy Dilemma

Approximately 700,0004,5 American men receive a negative prostate biopsy result; however approximately 25%6-8 of these results are false-negative. Under the current standard of care, prostate biopsy procedures collect 10-12 needle biopsy cores on average, effectively sampling less than 1% of a man's prostate. This approach leaves men at risk of occult cancer, leading to a high rate of repeat biopsies, often on cancer-free men. Prostate BioStrat® can help distinguish patients who have a true-negative biopsy from those who may have occult cancer. The test helps clinicians' rule-out prostate cancer-free men from undergoing unnecessary repeat biopsies and, helps rule-in high risk patients who may require repeat biopsies and potential treatment. TMPRSS2-ERG gene fusions are common genomic aberrations in prostate cancer and are found in up to 50% of prostate tumors and 0% in benign prostate tissue.9,10 It is believe that the TMPRSS2-ERG fusion is an early event in the development of invasive PCA.11

The detection of TMPRSS2-ERG by FISH is a very specific and sensitive assay for fusion positive prostate cancer. This can be an extremely useful ancillary test in deciding if re-biopsy is needed, especially in the setting of a negative tumor-free biopsy but suspicion for prostate cancer remains (i.e., abnormal DRE, elevated PSA and positive family history).

Problematic Prostate Needle Core Biopsies

Prostate BioStrat® FISH assays are useful adjuncts in confirming prostatic carcinoma that either lacks diagnostic, qualitative or quantitative features or that has an unusual morphologic pattern or is in the setting of prior treatment. A significant clinical implication for this finding is the assessment of TMPRSS2-ERG fusion status in problematic prostate needle core biopsies with high grade prostatic intraepithelial neoplasia (HGPIN) and adjacent small atypical glands.

TMPRSS2-ERG fusion was observed in a subset of high grade PIN lesions intermingling with prostate cancer with the same fusion pattern. TMPRSS2-ERG fusion was not observed in high grade PIN lesions geographically distant to prostate cancer, even if the cancer from the same individual demonstrated the TMPRSS2-ERG fusion. Hence, it is believed these high grade PIN lesions are a subset of true precursors for TMPRSS2-ERG positive prostate cancer.

Prostate BioStrat® for Determining Prostate Cancer Prognosis

Prostate FISH analysis provides information on molecular targets present in a prostate cancer for which are believed to be of prognostic significance based on the published literature. Given this information, prostate FISH results, along with standard clinicopathologic parameters, can be used as an aid to help stratify patients into favorable-, and unfavorable-risk groups for the likelihood of prostate cancer progression. Patients stratified into the unfavorable-risk group are more likely to benefit from more aggressive and/or additional therapy as opposed to those patients in the favorable-risk group who may respond to monotherapy or choose active surveillance.

Patients stratified into the unfavorable-risk group are more likely to benefit from more aggressive and/or additional therapy as opposed to those patients in the favorable-risk group who may respond to monotherapy or choose active surveillance.

The Prostate BioStrat® Advantage

The Prostate BioStrat® can help distinguish patients who have true-negative biopsy from those who may have occult cancer thereby sparing the vast majority of cancer-free men from unnecessary repeat biopsies. Similarly, prostate FISH is a valuable adjunct in establishing a definitive diagnosis in problematic prostate needle core biopsies with high grade PIN and adjacent small atypical glands.

The Prostate BioStrat® Assay can be a useful addition to the commonly used risk stratification grouping developed by D'Amico et al., which segregates patients diagnosed with prostate cancer into low-, intermediate-, and high-risk categories based on preoperative PSA, clinical stage and Gleason score.12

A favorable FISH hybridization pattern among patients presenting as low-risk (biopsy Gleason <=6, PSA <=10 ng/mL, clinical stage T1c, T2a) may serve to further strengthen the clinicopathologic assessment of less aggressive disease and provide added confidence in management decisions, especially when considering active surveillance. In contrast, an unfavorable FISH hybridization pattern may serve to appropriately heighten awareness of potentially aggressive disease inappropriately categorized as low-risk.

Assessing patients in the intermediate-risk group is particularly challenging given the extensive heterogeneity inherent in this risk grouping. With aid of the Prostate BioStrat® Assay, the patients lumped in the intermediate risk group can be assessed a favorable- or unfavorable-risk prior to prostate cancer treatment selection.

Unlike prostatectomy patients, patients considering radiotherapy (EBRT or brachytherapy), cryotherapy, or high intensity focused ultrasound (HIFU), will only have one histopathologic examination of their tumor as radiotherapy/cryotherapy/HIFU treatments destroy the tissue. Prostate BioStrat® provides a unique perspective on these patients' disease severity, prior to therapy, which otherwise would be unavailable.

Ordering

Please contact BioVantra Client Support Center at (866) 301-0960 to arrange for Prostate BioStrat® Assay testing. Our experienced Client Support Team can assist with:

  • Prostate BioStrat® Assay Requisition
  • Sample requirements
  • Logistics and specimen transportation
  • Testing methodology
  • Report delivery, status or interpretation
  • Expert oncology and pathology consultations
  • Requests for BioVantra literature and scientific references

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References

  1. McNeal JE, Villers AA, Redwine EA, Freiha FS and Stamey TA: Capsular penetration in prostate cancer. Significance for natural history and treatment. Am J Surg Pathol. 14: 240-7, 1990.
  2. Partin AW, Kattan MW, Subong EN, Walsh PC, Wojno KJ, Oesterling JE, Scardino PT and Pearson JD: Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA. 277: 1445-51, 1997.
  3. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI and Pearson JD: Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology. 58: 843-8, 2001.
  4. NCI. Cancer Trends Progress Report - 2011/2012 Update. 2012; http://progressreport.cancer.gov.
  5. NCI. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). 2012; http://seer.cancer.gov/csr/1975_2009_pops09/.
  6. Kronz JD, Allan CH, Shaikh AA, Epstein JI. Predicting cancer following a diagnosis of high-grade prostatic intraepithelial neoplasia on needle biopsy: data on men with more than one follow-up biopsy. Am J Surg Pathol. Aug 2001;25(8):1079-1085.
  7. Babaian RJ, Toi A, Kamoi K, et al. A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy. J Urol. Jan 2000;163(1):152-157.
  8. Ravery V, Goldblatt L, Royer B, Blanc E, Toublanc M, Boccon-Gibod L. Extensive biopsy protocol improves the detection rate of prostate cancer. J Urol. Aug 2000;164(2):393-396.
  9. Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene. Jul 5 2007;26(31):4596-4599.
  10. Mosquera JM, Mehra R, Regan MM, et al. Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States. Clin Cancer Res. Jul 15 2009;15(14):4706-4711.
  11. Perner S, Mosquera JM, Demichelis F, et al. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. Jun 2007;31(6):882-888..

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