A 70% cut-off for MYC protein expression in diffuse large B cell lymphoma identifies a high-risk group of patients
Marita Ziepert, Stefano Lazzi, Raffaella Santi, Federica Vergoni, Massimo Granai, Virginia Mancini, Annette M. Staiger, Heike Horn, Markus Löffler, Viola Pöschel, Gerhald Held, Gerald Wulf, Lorenz Trümper, Norbert Schmitz, Andreas Rosenwald, Elena Sabattini, Kikkeri N. Naresh, Harald Stein, German Ott, Lorenzo Leoncini
Abstract
We recently examined the reproducibility of MYC and BCL-2 immunohistochemical (IHC) scoring and the impact of high expression of MYC and BCL-2 (double expresser status, DE) on survival and progression in a large retrospective cohort of aggressive B-cell lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or R-CHOP-like regimens. 1 We found that IHC scoring for MYC and BCL-2 was highly reproducible when cut-off values of 70% for MYC and 50% for BCL-2 were used. This threshold also predicted the presence of gene rearrangements identifying MYC translocations in 88% of cases. Patients with dual MYC expression of 70% and BCL-2 expression of 50% showed a significantly inferior clinical course and, therefore, represent candidates for novel treatment modalities. n these trials, patients underwent R-CHOP-14 if >60 years of age and R-CHOEP/R-MegaCHOEP if 60 years of age. In the MegaCHOEP trial reported by Schmitz et al., 4 no significant differences in outcome between R-CHOEP-14 and R-MegaCHOEP had been observed, but to date, no randomized trial has been conducted to answer if R-CHOEP in younger patients is superior in comparison with R-CHOP. In a subgroup analysis for young low-risk patients from the MInT trial reported by Pfreundschuh et al., 5 no difference in outcome was observed between R-CHOEP-21 and R-CHOP-21. In elderly patients, the Cunningham trial 6 revealed that the outcome of R-CHOP-14 is not better than that of R-CHOP-21. In the German cohort of 428 patients with MYC and BCL-2 IHC scoring available, 104 cases (24%)