DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20191665

Prognostic impact of BCL2, BCL6 and MYC status in de novo diffuse large B-cell lymphoma: a regional study of 43 patients

Dudu Solakoglu Kahraman, Gulden Diniz, Cengiz Ceylan, Faruk Recep Ozalp, Yetkin Koca, Sumeyye Ekmekci, Duygu Ayaz, Sevil Sayhan

Abstract


Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We aimed to evaluate the status of MYC, BCL2, BCL6 in patients with DLBCL.

Methods: Herein, we have investigated the prognostic relevance of MYC, BCL2 and BCL6 from 43 de novo DLBCL patients.

Results: In this study, protein overexpression of BCL2 and BCL6 was encountered in 46.5% (n=20) and 27.9% (n=12) of the tumors, respectively.  Rearrangements in MYC, BCL6, and BCL2 were detected in 9.3% (n=4), 25.6% (n=11), and 4.7% (n=2) of the cases, respectively. Any statistically significant difference could not be found between Bcl-2, Bcl-6 expression, C-MYC rearrangement and the survival.

Conclusions: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, so more mechanism-based therapy should be explored. A larger study is warranted to better understand the immunophenotypic and molecular features of DLBCL and their respective impact on patient survival.


Keywords


Diffuse large B-cell lymphoma, Fluorescence in situ hybridization, Immunohistochemistry, Prognosis, MYC, BCL6, BCL2

Full Text:

PDF

References


Yan LX, Liu YH, Luo DL, Zhang F, Cheng Y, Luo XL, et al. MYC expression in concert with BCL2 and BCL6 expression predicts outcome in Chinese patients with diffuse large B-cell lymphoma, not otherwise specified. PLOS One. 2014;9(8):e104068.

Ye Q, Xu-Monette ZY, Tzankov A, Deng L, Wang X, Manyam GC, et al. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma. Oncotarget. 2016;7(3):2401-16.

Pedersen MO, Gang AO, Poulsen TS, Knudsen H, Lauritzen AF, Nielsen SL, et al. Double-hit BCL2/MYC translocations in a consecutive cohort of patients with large B-cell lymphoma-A single centre's. Eur J Hematol. 2014;92:42-8.

The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329:987-94.

Akkaya B, Salim O, Akkaya H, Ozcan M, Yucel OK, Erdem R, et al. C-MYC and BCL2 translocation frequency in diffuse large B-cell lymphomas: A study of 97 patients. Indian J Pathol Microbiol. 2016;59(1):41-6.

Aukema SM, Siebert R, Schuuring E, van Imhoff GW, Kluin-Nelemans HC, Boerma EJ, et al. Double-hit B-cell lymphomas. Blood. 2011;117:2319-31.

Sinha P, Hutter G, Kottgen E, Dietel M, Schadendorf D, Lage H. Increased expression of epidermal fatty acid binding protein, cofilin, and 14-3-3-sigma (stratifin) detected by two-dimensional gel electrophoresis, mass spectrometry and microsequencing of drug-resistant human adenocarcinoma of the pancreas. Electrophoresis. 1999;20:2952-60.

Xu-Monette ZY, Dabaja BS, Wang X, Tu M, Manyam GC, Tzankov A, et al. Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Modern Pathol. 2015 Dec;28(12):1555.

He M, Chen K, Li S, Zhang S, Zheng J, Hu X, et al. Clinical significance of “double-hit” and “double-protein” expression in primary gastric B-cell lymphomas. J Cancer. 2016;7(10):1215.

Tibiletti MG, Martin V, Bernasconi B, Del Curto B, Pecciarini L, Uccella S, et al. BCL2, BCL6, MYC, MALT 1, and BCL10 rearrangements in nodal diffuse large B-cell lymphomas: a multicenter evaluation of a new set of fluorescent in situ hybridization probes and correlation with clinical outcome. Human Pathol. 2009;40(5):645-52.

Barrans S, Crouch S, Smith A, Turner K, Owen R, Patmore R, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28:3360-5.

Valera A, Lopez-Guillermo A, Cardesa-Salzmann T, Climent F, Gonzalez-Barca E, Mercadal S, et al. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Haematol. 2013;98:1554-62.

Perry AM, Mitrovic Z, Chan WC. Biological prognostic markers in diffuse large B-cell lymphoma. Cancer Control. 2012 Jul;19(3):214-26.

Pfreundschuh M. Growing importance of MYC/BCL2 immunohistochemistry in diffuse large B-cell lymphomas. J Clin Oncol. 2012;30:3433-5.

Slack GW, Gascoyne RD. MYC and aggressive B-cell lymphomas. Adv Anat Pathol. 2011;18:219-28.

Akyurek N, Uner A, Benekli M, Barista I. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Cancer. 2012;118:4173-83.

Cuccuini W, Briere J, Mounier N, Voelker HU, Rosenwald A, Sundstrom C, et al. MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation. Blood. 2012;19(20):4619-24.

Peng F, Guo L, Yao WK, Zheng Y, Liu Y, Duan XM, et al. Identification of prognostic factors in patients with diffuse large B-cell lymphoma. Indian J Pathol Microbiol. 2017 Jan-Mar;60(1):87-91.

Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013;121:2253-63.

Akasaka T, Akasaka H, Ueda C, Yonetani N, Maesako Y, et al. Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene. J Clin Oncol. 2000;18:510-8.

Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012 Oct 1;30(28):3452.

Yoon SO, Jeon YK, Paik JH, Kim WY, Kim YA, Kim JE, et al. MYC translocation and an increased copy number predict poor prognosis in adult diffuse large B‐cell lymphoma (DLBCL), especially in germinal centre‐like B cell (GCB) type. Histopathology. 2008 Aug;53(2):205-17.

Kawamoto K, Miyoshi H, Yoshida N, Nakamura N, Ohshima K, Sone H, et al. MYC translocation and/or BCL 2 protein expression are associated with poor prognosis in diffuse large B‐cell lymphoma. Cancer science. 2016 Jun;107(6):853-61.

Vitolo U, Gaidano G, Botto B, Volpe G, Audisio E, Bertini M, et al. Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: clinical relevance in 71 patients. Annals Oncology. 1998 Jan 1;9(1):55-61.

Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-42.

Stein RA, Warnke WC, Chan ES, Jaffe JKC, Chan KC, Gatter, et al. Diffuse large B-cell lymphoma, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, et al. (Eds.), WHO classification of tumours of haematopoietic and lymphoid tissues, IARC, Lyon, France; 2008:233-237.

Chang ST, Chen SW, Ho CH, Kuo CC, Sakata S, Takeuchi K, et al. Immunophenotypic and genetic characteristics of diffuse large B-cell lymphoma in Taiwan. J Formosan Med Association. 2016 Nov 1;115(11):961-7.