Purpose: In this study, we investigated the prevalence of CD79B  and MYD88  mutations and their relation to clinical characteristics in a cohort of Chinese patients with primary testicular diffuse large B cell lymphoma (PT-DLBCL).
Patients and methods: We examined the mutational status of CD79B  and MYD88  by Sanger sequencing, and the gene amplification and protein expression of MYD88 in tissue samples from 30 cases of PT-DLBCL by quantitative polymerase chain reaction and immunohistochemistry, respectively. Western blotting was used to analyze phosphorylated STAT3 (p-STAT3) and phosphorylated p65 (p-p65) protein expression in cell lines harboring retroviral constructs for WT MYD88  or MYD88  mutant.
Results: Immunophenotypically, MYD88 protein staining was positive in 26/30 (86.67%) cases, and 23/30 (76.7%) cases tested positive for p65 in the nucleus. Genetically, CD79B  mutation was found in 13/30 (43.3%) cases, whereas the MYD88 ^L265P mutation was found in 18/30 (60.0%) cases. Interestingly, CD79B  and MYD88  mutations were more prevalent in the non-germinal center B cell (GCB) subtype (83.3% and 76.9%, respectively) and were relatively rare in the GCB subtype (16.7% and 23.1%, respectively). Furthermore, although MYD88  was significantly amplified in PT-DLBCL, the amplification status showed no correlation with its mutational status and protein expression. Clinicopathological comparison between the mutant and wild-type group showed that both CD79B  mutation and MYD88 ^L265P were not significantly correlated with age, anatomical site, Ann Arbor stage, non-GCB/GCB subtype, p65 protein expression, BCL-2 protein expression, or BCL-2/c-MYC double expression (P >0.05). Survival analyses showed that high IPI and advanced stage (stage III–IV) associated with worse outcome (P <0.05). The expression of p-STAT3 and p-p65 protein was upregulated in the mutant group, indicating that MYD88  mutant activated NF-κB and JAK–STAT3 signaling.
Conclusion: Our results suggest that MYD88  and CD79B  mutations are important drivers of immune-privileged site-associated DLBCL and highlight potential therapeutic targets for personalized treatment.
Keywords: primary testicular lymphoma, CD79B , MYD88 , mutation, diffuse large B cell lymphoma, gene amplification