cMYC and BCL2 Status (Lymphoma)

Methodology

The Vysis cMYC and BCL2 Break Apart FISH assays are a diagnostic and prognostic guide that, in combination with other actual prognostic factors, can be used to determine the treatment of patients with follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) eligible for R-CHOP therapy.

Test description:

cMYC (8q24) Gene Rearrangement

  • Fluorescence in situ hybridization (FISH)
  • Vysis cMYC Break Apart FISH Probe Kit (Abbott, CE-IVD)

BCL2 (18q21) Gene rearrangement

  • Fluorescence in situ hybridization
  • Vysis BCL2 Break Apart FISH Probe Kit (Abbott, CE-IVD)

Clinical Implication

High-grade B-cell lymphomas (HGBLs) are a biologically heterogeneous group in which various gene alterations have been reported1. Several studies have showed that the presence of cMYC aberrations identifies a patient subset with a very poor prognosis, particularly when there is concomitant rearrangement of BCL2, a condition referred to as "double hit” DLBCL2,3. cMYC translocations confer a worse prognosis in patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), both in combination with and without rituximab4. A correct characterization is very important because cMYC and BCL2 translocation not only have diagnostic value but they are also a powerful prognostic indicator in several lymphomas5.

Specimen Requirements

Acceptable specimens for the assay are formalin (10% buffered formalin)-fixed (6-48 hours), paraffin-embedded lymphoma tissue specimens. Sectioned slides must be analyzed within 24 months after sectioning date.
Volume
1 representative paraffin block is preferred. Alternatively, 5 unstained freshly sectioned tissue sections of 4 µm thickness on positively charged slides are accepted (1 slide for H&E staining, 2 slides of cMYC and 2 slides for BCL2 FISH testing).

Storage and Shipment Instructions

Maintain and ship specimens at ambient temperature.

Limitations

Fixatives other than buffered formalin, prolonged fixation time, decalcification or exposure to severe heath or chemicals may give rise to inadequate results.

Special Requirements

None

Turn-Around Time

BCL2 FISH: 5-7 business days
cMYC FISH: 5-7 business days
cMYC and BCL2 FISH assay: 7-10 business days

References

  1. Sesques and Johnson. Approach to the diagnosis and treatment of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements. Blood. 2017;129(3):280-288
  2. Thomas DA et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569–1580.
  3. Lin P et al. Prognostic value of MYC rearrangement in cases of B cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Cancer. 2012 Mar 15;118(6):1566-73.
  4. Pfreundschuh M. Growing Importance of MYC/BCL2 Immunohistochemistry in Diffuse Large B-Cell Lymphomas. J. Clin. Oncol. 2012; 30(28): 3433-3435
  5. Aquino et al. Detection of MYC rearranged by fluorescence in situ hybridization FISH: a diagnostic tool. WCRJ 2014;1(4):e362