PROGNOSTIC VALUE OF IMMUNOHISTOCHEMICAL MARKERS IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA

Arina Martynchyk, Vitaliy Gurianov, Iryna Kriachok

Abstract


Diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease, but standard treatment is not effective enough for all patients. That is why so important to identify high risk patients who need more aggressive therapy at the time of diagnosis. Nowadays prognosis for patients with DLBCL is based on International prognostic index (IPI). However, this index consists of only clinical parameters and does not include the biological characteristics of the tumour. Immunohistochemistry (IHC) markers could also play a prognostic role. There are some publications regarding predictive and prognostic role of expression of Bcl-2, Bcl-6, MUM1, CD10 and CD30, but their results are controversial. The aim of our study was to analyze prognostic role of these markers, to compare survival of patients with positive and negative expression of these markers and to build a prognostic model which include biological parameters for identifying high risk patients. There were statistically significant differences in EFS between the group of patients with negative and positive expression of CD10 (51.5 % versus 72.5 %, р=0.01) and in OS between the group of patients with negative and positive expression of Bcl-6 (61.1 % versus 79.6 %, р=0.03). Six-factors nonlinear neural network prediction model (MLP_6) was built. The sensitivity of the model is 63.2 % (95 % CІ 49.3 % – 75.6 %), specificity – 85.2 % (95 % CІ 79.1 % – 90.1 %). Prognostic factors include negative IHC expression of Bcl-6, CD10, non-GCB molecular subtype (according to algorithm Hans), gender (male), advanced Ann-Arbor stages, >2extranodal involvement. Our nonlinear neural network prediction model could improve prognostic role of IPI by adding of biological tumour characteristics (IHC expression of CD10, Bcl-6, molecular subtype by IHC algorithm).


Keywords


diffuse large B-cell lymphoma; prognosis; predictive model; biological characteristics

Full Text:

PDF

References


Swerdlow, S. H., Campo, E., Pileri, S. A., Harris, N. L., Stein, H., Siebert, R. et. al. (2016). The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood, 127 (20), 2375–2390. doi: 10.1182/blood-2016-01-643569

Sehn, L. H. (2014). Diffuse large B-cell lymphoma: one treatment no longer fits all. Oncology, 28 (4), 334–336.

A Predictive Model for Aggressive Non-Hodgkin's Lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project (1993). New England Journal of Medicine, 329 (14), 987–994. doi: 10.1056/nejm199309303291402

Van Imhoff, G. W., Boerma, E.-J. G., van der Holt, B., Schuuring, E., Verdonck, L. F., Kluin-Nelemans, H. C., Kluin, P. M. (2006). Prognostic Impact of Germinal Center–Associated Proteins and Chromosomal Breakpoints in Poor-Risk Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology, 24 (25), 4135–4142. doi: 10.1200/jco.2006.05.5897

Amen, F., Horncastle, D., Elderfield, K., Banham, A. H., Bower, M., Macdonald, D. et. al. (2007). Absence of cyclin-D2 and Bcl-2 expression within the germinal centre type of diffuse large B-cell lymphoma identifies a very good prognostic subgroup of patients. Histopathology, 51 (1), 70–79. doi: 10.1111/j.1365-2559.2007.02721.x

Hallack Neto, A. E., Dulley, F. L., Coelho Siqueira, S. A., Pracchia, L. F., Belesso, M., Saboya, R. et. al. (2008). Prognostic impact of diffuse large B-cell lymphoma subgroups in patients undergoing autologous SCT. Bone Marrow Transplantation, 43 (4), 323–325. doi: 10.1038/bmt.2008.330

Kryachok, I., Martynchyk, A. V., Filonenko, K., Grabovoy, A. N., Antoniuk, S. A., Tytorenko, I. et. al. (2016). The predictive value of immunohistochemical expression of Bcl-2, Bcl-6, MUM1, CD10 and CD30 in patients with diffuse large cell lymphoma. Annals of Oncology, 27, 923. doi: 10.1093/annonc/mdw375.18

Berglund, M., Thunberg, U., Amini, R. M. et. al. (2005). Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis. Modern Pathology, 18, 1113–1120.

Sjo, L. D., Poulsen, C. B., Hansen, M., Moller, M. B., Ralfkiaer, E. (2007). Profiling of diffuse large B-cell lymphoma by immunohistochemistry: identification of prognostic subgroups. European Journal of Haematology, 79 (6), 501–507. doi: 10.1111/j.1600-0609.2007.00976.x

Fabiani, B., Delmer, A., Lepage, E., Guettier, C., Petrella, T. et. al. (2004). CD10 expression in diffuse large B-cell lymphomas does not influence survival. Virchows Archiv, 445 (6), 545–551. doi: 10.1007/s00428-004-1129-7

Barrans, S. L., O’Connor, S. J. M., Evans, P. A. S., Davies, F. E., Owen, R. G., Haynes, A. P. et. al. (2002). Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma. British Journal of Haematology, 117 (2), 322–332. doi: 10.1046/j.1365-2141.2002.03435.x

Wilson, W. H., Dunleavy, K., Pittaluga, S., Hegde, U., Grant, N., Steinberg, S. M. et. al. (2008). Phase II Study of Dose-Adjusted EPOCH and Rituximab in Untreated Diffuse Large B-Cell Lymphoma With Analysis of Germinal Center and Post-Germinal Center Biomarkers. Journal of Clinical Oncology, 26 (16), 2717–2724. doi: 10.1200/jco.2007.13.1391

Muris, J., Meijer, C., Vos, W., van Krieken, J., Jiwa, N., Ossenkoppele, G., Oudejans, J. (2006). Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. The Journal of Pathology, 208 (5), 714–723. doi: 10.1002/path.1924

Horn, H., Ziepert, M., Becher, C., Barth, T. F. E., Bernd, H.-W. et. al. (2013). MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood, 121 (12), 2253–2263. doi: 10.1182/blood-2012-06-435842

Colomo, L., Lopez-Guillermo, A., Perales, M. et. al. (2003). Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. Blood, 101 (1), 78–84. doi: 10.1182/blood-2002-04-1286

Linderoth, J., Jerkeman, M., Cavallin-Stahl, E. et. al. (2003) Immunohistochemical expression of CD23 and CD40 may identify prognostically favorable subgroups of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Study. Clinical Cancer Research, 9 (2), 722–728.

Hans, C. P., Weisenburger, D. D., Greiner, T. C. et. al. (2004). Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood, 103 (1), 275–282. doi: 10.1182/blood-2003-05-1545

Kanda, Y. (2012). Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplantation, 48 (3), 452–458. doi: 10.1038/bmt.2012.244

Liah, Y., Gurianov, G. (2012). Mathematical modeling in solving classification problems in biomedicine. Ukrainskyi zhurnal telemedycyny ta medychnoi telematyky, 10 (2), 69–76.

Petrie, A., Sabin, C. (2009). Medical Statistics at a Glance. Wiley-Blackwell, 180.




DOI: http://dx.doi.org/10.21303/2504-5679.2018.00564

Refbacks

  • There are currently no refbacks.




Copyright (c) 2018 Arina Martynchyk, Vitaliy Gurianov, Iryna Kriachok

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2504-5679 (Online), ISSN 2504-5660 (Print)