Clinical Services

Prostate BioStrat™ Assay

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.

Occurrence of a variety of chromosomal and genetic alterations has been discovered in prostate cancer. Two significant genetic alterations identified in prostate cancer include gain of the band 8q24 and loss of heterozygosity of 8p21-22.4-6 Gain of 8q24 has been shown to be a common event in prostate cancer, frequently accompanied by 8p21-22 loss of heterozygosity.7-8 It is believed that genes mapped to 8p may be involved in the early stage of tumorigenesis.6 Over-representation of C-MYC has been associated with prostate cancer progression.9 Multiple probe analysis using DNA FISH probes for 8p22 (LSI LPL), C-MYC (LSI C-MYC) and the centromere of chromosome 8 (CEP 8) has shown that prostate carcinomas have frequent genetic abnormalities of chromosome 8, loss of 8p22 and gains of chromosome 8. Use of multiple FISH probes within a single reagent provides an excellent tool for determining the occurrence of these multiple genetic events on a cell by cell basis in a variety of tissue specimen preparations.

Introduction to Prostate BioStrat™ Assay

The Prostate BioStrat™ Assay is a fluorescence in situ hybridization (FISH) assay that was designed to help assess the severity of prostate cancer at the time of diagnosis. It consists of fluorescently labeled DNA probes to the pericentromeric region of chromosomes 8 (aqua) and to the 8p21-22 (orange) and 8q24 (green) loci containing the lipoprotein lipase (LPL) and C-MYC genes, respectively.

Results from the assay can be used 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.

Criteria for Prostate BioStrat™ Abnormality

In a normal cell hybridized with the Prostate BioStrat™ probe set, the expected pattern is the two orange, two green and two aqua signal pattern. In an abnormal cell, combinations of copies of the three probe signals may be observed. Copy numbers of more or less than two of any probe indicates chromosome or gene gain or loss, respectively. Less than two copies of the LSI LPL or multiple copies of the LSI C-MYC probe relative to chromosome 8 copy number indicates loss of the LPL region and gain of the C-MYC region, respectively, relative to the chromosome 8 copy number.

An LSI or CEP 8 is classified as normal if less than 10% of nuclei have 3 or more signals and less than 55% of nuclei have 0 or 1 signal. CEP 8 is classified as loss if 55% or more nuclei have 0 or 1 signal. An LSI is classified as loss, either if 55% or more nuclei have 0 or 1 signal or if the LSI/CEP 8 ratio is less than 0.85. CEP 8 is classified as gain if 10% or more nuclei have 3 or more signals. An LSI is classified as gain if 10% or more nuclei have 3 or more signals or if the LSI/CEP 8 ratio is more than 1.3. An LSI is classified as additional increase (AI) if 10% or more nuclei have 3 or more signals and the LSI/CEP 8 ratio is more than 1.3.

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Prostate BioStrat™ Images

The following examples of patient specimens demonstrate both the clinical utility of the Prostate BioStrat™ Assay as well as its simplicity of interpretation.


Figure 1

Figure 2

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.10-11 Specifically, assessing loss or gain of the 8p22 locus of chromosome 8, the centromere of chromosome 8, and the 8q24 locus provides a prognostic indicator for prostate cancer.

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. Accordingly, prognosis of a patient is determined to be unfavorable when the hybridization pattern indicates loss of the 8p22 locus, gain of chromosome 8, and additional increase of 8q24 copy number relative to centromere copy number.

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™ Assay is a valuable adjunct 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) 627-8221 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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Sample Report

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. Bova GS, Carter BS, Bussemakers MJ, Emi M, Fujiwara Y, Kyprianou N, Jacobs SC, Robinson JC, Epstein JI, Walsh PC et al.: Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. Cancer Res. 53: 3869-73, 1993.
  5. Kagan J, Stein J, Babaian RJ, Joe YS, Pisters LL, Glassman AB, von Eschenbach AC and Troncoso P: Homozygous deletions at 8p22 and 8p21 in prostate cancer implicate these regions as the sites for candidate tumor suppressor genes. Oncogene. 11: 2121-6, 1995.
  6. Emmert-Buck MR, Vocke CD, Pozzatti RO, Duray PH, Jennings SB, Florence CD, Zhuang Z, Bostwick DG, Liotta LA and Linehan WM: Allelic loss on chromosome 8p12-21 in microdissected prostatic intraepithelial neoplasia. Cancer Res. 55: 2959-62, 1995.
  7. Cher ML, MacGrogan D, Bookstein R, Brown JA, Jenkins RB and Jensen RH: Comparative genomic hybridization, allelic imbalance, and fluorescence in situ hybridization on chromosome 8 in prostate cancer. Genes Chromosomes Cancer. 11: 153-62, 1994.
  8. Visakorpi T, Kallioniemi AH, Syvanen AC, Hyytinen ER, Karhu R, Tammela T, Isola JJ and Kallioniemi OP: Genetic changes in primary and recurrent prostate cancer by comparative genomic hybridization. Cancer Res. 55: 342-7, 1995.
  9. Jenkins RB, Qian J, Lieber MM and Bostwick DG: Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. Cancer Res. 57: 524-31, 1997.
  10. Tsuchiya N, Slezak JM, Lieber MM, Bergstralh EJ and Jenkins RB: Clinical significance of alterations of chromosome 8 detected by fluorescence in situ hybridization analysis in pathologic organ-confined prostate cancer. Genes Chromosomes Cancer. 34: 363-71, 2002.
  11. Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ and Jenkins RB: Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. J Natl Cancer Inst. 91: 1574-80, 1999.
  12. D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ et al.: Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 280: 969-74, 1998.

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