Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large b-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubiciB, vincristine, and prednisone
Journal of Clinical Oncology, 06/06/2012
Green TM et al. – The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.Methods
- Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2.
- FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002).
- On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL.
- The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised 29% of the patients.
- DHS 2 was significantly associated with lower complete response rate (P = .004), shorter OS (P < .001), and shorter progression-free survival (PFS; P < .001).
- The highly significant correlation with OS and PFS was maintained in multivariate models that controlled for the International Prognostic Index and the cell-of-origin subtype (OS, P < .001; PFS, P < .001).
- DHS was validated in an independent cohort of 116 patients who were treated with R-CHOP.