MYC in addition to BCL2 or BCL6 protein coexpression ‘double-expressor’ contributes to the inferior overall survival in a series of Egyptian patients with diffuse large B-cell lymphoma

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Abstract

Background and aim

Non-Hodgkin diffuse large B-cell lymphoma having MYC in addition to BCL2 and/or BCL6 rearrangements was recently defined as double/triple-hit lymphoma. Diagnosis by fluorescence in-situ hybridization is sensitive and specific but is time consuming and expensive. We aimed in this study to record cases of double/triple expressor diffuse large B-cell lymphoma (DLBCL) that express MYC, BCL2 and/or BCL6 by immunohistochemistry to help in selecting the patients who should be further tested for fluorescence in-situ hybridization.

Patients and methods

Immunohistochemical examination for BCL2, BCL6 and MYC was performed on paraffin blocks of 24 patients with primary DLBCL, treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Cases were given one point for each of the markers expressed at or above the cutoff point and classified according to double hit score (DHS) to non-double expressor (low DHS=0 or 1) and double expressor (high DHS=2). No triple expressors were detected. The revised international prognostic index was assigned into low (≤2) and high (3–5).

Results

Patients with double-expressor DLBCL were significantly associated with higher lactate dehydrogenase level, higher revised international prognostic index, poorer response to R-CHOP, high Ki-67, and shorter progression-free survival and overall survival. Patients with high international prognostic index scores were associated with significantly shorter progression-free survival and overall survival but not with response to R-CHOP and Ki-67 proliferation.

Conclusion

This study advocates immunostaining for MYC, BCL2 and BCL6 as a screening tool for DLBCL cases to detect the subset of double/triple expressors with predicted inferior outcome, which may necessitate a more aggressive frontline treatment.

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