Prevalence And Clinical Significance Of Oncogenic CD79B And MYD88 Mutations In Primary Testicular Diffuse Large B-Cell Lymphoma: A Retrospective Study In China

Yan-Ping Chen; Long-Feng Ke; Jian-Ping Lu; Jian-Chao Wang; Wei-Feng Zhu; Fang-Fang Chen; Shao-Feng Lin; Chun-Wei Xu; Mei-Juan Wu; Gang Chen

doi:10.2147/OTT.S222189

Prevalence And Clinical Significance Of Oncogenic CD79B And MYD88 Mutations In Primary Testicular Diffuse Large B-Cell Lymphoma: A Retrospective Study In China

Onco Targets Ther. 2019 Nov 26:12:10165-10175. doi: 10.2147/OTT.S222189. eCollection 2019.

Authors

Yan-Ping Chen^#^{1

2}, Long-Feng Ke^#³, Jian-Ping Lu¹, Jian-Chao Wang^{1

2}, Wei-Feng Zhu¹, Fang-Fang Chen³, Shao-Feng Lin⁴, Chun-Wei Xu³, Mei-Juan Wu⁵, Gang Chen^{1

2}

Affiliations

¹ Department of Pathology of Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, People's Republic of China.
² Department of Fujian Provincial Key Laboratory of Tumor Biotherapy, Fuzhou, Fujian 350014, People's Republic of China.
³ Department of Molecular Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian 350014, People's Republic of China.
⁴ Department of Thoracic Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, People's Republic of China.
⁵ Department of Pathology of Zhejiang Cancer Hospital, Hanzhou 310022, People's Republic of China.

^# Contributed equally.

Abstract

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: CD79B; MYD88; diffuse large B cell lymphoma; gene amplification; mutation; primary testicular lymphoma.