Association of AID and MUM1 by Immunohistochemistry in Diffuse Large B-Cell Lymphoma
Abstract
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with dysregulation of somatic hypermutation (SHM) and class switch recombination (CSR) have been known to contribute for its lymphomagenesis. Activation-induced cytidine deaminase (AID) enzyme plays a vital role for both processes. Multiple myeloma oncogene 1 (MUM1) is known to upregulate the AID expression in normal and pathological conditions. However, both AID and MUM1 expression association in DLBCL is still unexplored using immunohistochemistry method. We examined DLBCL samples and then retrospectively tested its correlation with clinical findings.
METHODS: A retrospective cohort study with 20 cases of DLBCL biopsy tissue with AID and MUM1 antibody was conducted. The samples were then classified into concordant (AID+/MUM1+ or AID-/MUM1-) and discordant group (AID-/MUM1+). The clinicopathological comparison was performed to observe any association between immunohistochemistry expression and clinical findings.
RESULTS: Among 20 samples of DLBCL, concordant expression rate of AID and MUM1 was 80% with kappa Cohen’s of 0.578 (p=0.004). A significant association was observed between AID and MUM1 expression with a prevalence ratio of 2.25 (95% CI: 1.08-4.67; p=0.008). Clinical characteristics were not significantly different between each group. Restricted mean survival time was shorter in the concordant group compared with the discordant group but statistically insignificant (21.16 vs. 22.5 months; p=0.531).
CONCLUSION: The result of this study showed the association between AID and MUM1 expression in DLBCL. However, whether the association may add further molecular heterogeneity of DLBCL is still to be confirmed by expanding the study.
KEYWORDS: AID, CSR, DLBCL, MUM1, SHM
Full Text:
PDFReferences
Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010; 362: 1417-29, CrossRef.
Reksodiputro AH. Multicentre epidemiology and survival study of B cell non hodgkin lymphoma patients in Indonesia. J Blood Disord Transfus. 2015; 6: 2-6, CrossRef.
Sujobert P, Salles G, Bachy E. Molecular classification of diffuse large B-cell lymphoma. Hematol Oncol Clin North Am. 2016; 30: 1163-77, CrossRef.
Miao Y, Medeiros LJ, Li Y, Li J, Young KH. Genetic alterations and their clinical implications in DLBCL. Nat Rev Clin Oncol. 2019; 16: 634-52, CrossRef.
Meiliana A, Dewi NM, Wijaya A. Cancer stem cell hypothesis: Implication for cancer prevention and treatment. Indones Biomed J. 2016; 8: 21-36, CrossRef.
Wang JH. The role of activation-induced deaminase in antibody diversification and genomic instability. Immunol Res. 2013; 55: 287-97, CrossRef.
Gu X, Shivarov V, Strout MP. The role of activation-induced cytidine deaminase in lymphomagenesis. Curr Opin Hematol. 2012; 19: 292-8, CrossRef.
Teater M, Dominguez PM, Redmond D, Chen Z, Ennishi D, Scott DW, et al. AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis. Nat Commun. 2018; 9: 222, CrossRef.
Kawamura K, Wada A, Wang JY, Li Q, Ishii A, Tsujimura H, et al. Expression of activation-induced cytidine deaminase is associated with a poor prognosis of diffuse large B cell lymphoma patients treated with CHOP-based chemotherapy. J Cancer Res Clin Oncol. 2016; 142: 27-36, CrossRef.
Arima H, Fujimoto M, Nishikori M, Kitano T, Kishimoto W, Hishizawa M, et al. Prognostic impact of activation-induced cytidine deaminase expression for patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2018; 59: 2085-95, CrossRef.
Hauser J, Grundström C, Kumar R, Grundström T. Regulated localization of an AID complex with E2A, PAX5 and IRF4 at the Igh locus. Mol Immunol. 2016; 80: 78-90, CrossRef.
Willis SN, Good-Jacobson KL, Curtis J, Light A, Tellier J, Shi W, et al. Transcription factor IRF4 regulates germinal center cell formation through a B cell-intrinsic mechanism. J Immunol. 2014; 192: 3200-6, CrossRef.
Lu TX, Miao Y, Wu JZ, Gong QX, Liang JH, Wang Z, et al. The distinct clinical features and prognosis of the CD10+ MUM1+ and CD10- Bcl6- MUM1- diffuse large B-cell lymphoma. Sci Rep. 2016; 6: 20465, CrossRef.
Sofo-Hafizovic A, Chikha A, Gojak R, Hadzimesic A. Expression IRF/MUM1 >25% predictor to three-year survival of diffuse large B cell lymphoma in the immunochemotherapy era. Med Arch. 2016; 70: 342-7, CrossRef.
Coutinho R, Clear AJ, Owen A, Wilson A, Matthews J, Lee A, et al. Poor concordance among nine immunohistochemistry classifiers of cell-of-origin for diffuse large B-cell lymphoma: Implications for therapeutic strategies. Clin Cancer Res. 2013; 19: 6686-95, CrossRef.
Shi Y, Han Y, Yang J, Liu P, He X, Zhang C, et al. Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin: Analysis of 1,085 WHO classified cases in a single institution in China. Chinese J Cancer Res. 2019; 31: 152-61, CrossRef.
Horvat M, Zadnik V, Južnič Šetina T, Boltežar L, Pahole Goličnik J, Novaković S, et al. Diffuse large B-cell lymphoma: 10 years’ real-world clinical experience with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone. Oncol Lett. 2018; 15: 3602-9, CrossRef.
Ochiai K, Maienschein-Cline M, Simonetti G, Chen J, Rosenthal R, Brink R, et al. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity. 2013; 38: 918-29, CrossRef.
Snak Y, Indrawati, Widayati K, Arfian N, Anggorowati N. Molecular subtypes, apoptosis and proliferation status in indonesian diffuse large B-cell lymphoma cases. Asian Pac J Cancer Prev. 2018; 19: 185-91, CrossRef.
Khodabakhshi AH, Morin RD, Fejes AP, Mungall AJ, Mungall KL, Bolger-Munro M, et al. Recurrent targets of aberrant somatic hypermutation in lymphoma. Oncotarget. 2012; 3: 1308-19, CrossRef.
Sha C, Barrans S, Cucco F, Bentley MA, Care MA, Cummin T, et al. Molecular high-grade B-cell lymphoma: Defining a poor-risk group that requires different approaches to therapy. J Clin Oncol. 2019; 37: 202-12, CrossRef.
Zhang J, Shi Y, Zhao M, Hu H, Huang H. Activation-induced cytidine deaminase overexpression in double-hit lymphoma: potential target for novel anticancer therapy. Sci Rep. 2020; 10: 14164, CrossRef.
DOI: https://doi.org/10.18585/inabj.v13i1.1421
Copyright (c) 2021 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute