Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL) (31% of all cases). Approximately half of patients with DLBCL are cured with current chemotherapy regimens. The purpose of this study was to evaluate BCl2 expression in 45 patients diagnosed with DLBCL of head and neck region and correlate the level of its immunohistochemical expression with different clinicopathological variables with emphasis upon patients’ age, gender, nodal or extra-nodal location of lymphoma, patients’ response to chemotherapy, progression-free survival (PFS) and overall survival (OS). A retrospective analysis of 45 patients diagnosed to have DLBCL. A cut off value of ≥ 50% protein expression denoted BCL2 positivity. Out of 45 cases, 36 cases (80%) revealed BCL2 positive expression and 9 cases (20%) were BCL2 negative. We found statistically significant differences in BCL2 expression regarding different patients’ responses to chemotherapy, patients’ OS and PFS (p ≤ 0.05). No statistically significant differences in BCL2 expression regarding the patients’ Ann Arbor clinical stage, age group and tumor site (nodal or extra-nodal, p > 0.05) using the Chi-square test. BCL2 expression was analyzed in relation to 5 years OS and PFS using Kaplan Meier curves and Log Rank test for survival analysis. Cases that demonstrated BCL2 positivity revealed shortened OS and PFS with highly statistically significant differences among the studied variables (p = 0.000). We also found that patients who respond well to the chemotherapeutic regimen had negative BCL2 expression, the differences were statistically significant (p = 0.015). In conclusion, BCL2 expression could be considered a predictor for patients’ chemotherapeutic response, OS and PFS.
References
[1]
Epstein, J.B., Epstein, J.D., Le, N.D. and Gorsky, M. (2001) Characteristics of Oral and Paraoral Malignant Lymphoma: A Population-Based Review of 361 Cases. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 92, 519-525. https://doi.org/10.1067/moe.2001.116062
[2]
Kemp, S., Gallagher, G., Kabani, S., Noonan, V. and O’Hara, C. (2008) Oral Non Hodgkin’s Lymphoma: Review of the Literature and World Health Organization Classification with Reference to 40 Cases. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 105, 194-201.
https://doi.org/10.1016/j.tripleo.2007.02.019
[3]
Mardi, K., Sharma, M., Bhardwaj, M., Rao, M., Pradesh, H., Mardi, K., et al. (2019) p53 expression in colorectal carcinomas and its correlation with clinic. Eduki hau blokeatuta dauka zure erakundeak/Contenido bloqueado por su organización. 2017-20.
[4]
Armitage, J.O. and Weisenburger, D.D. (1998) New Approach to Classifying Non-Hodgkin’s Lymphomas: Clinical Features of the Major Histologic Subtypes. Journal of Clinical Oncology, 16, 2780-2795. https://doi.org/10.1200/JCO.1998.16.8.2780
[5]
Coiffier, B. (2007) Rituximab Therapy in Malignant Lymphoma. Oncogene, 26, 3603-3613. https://doi.org/10.1038/sj.onc.1210376
[6]
Sehn, L.H., Berry, B., Chhanabhai, M., Fitzgerald, C., Gill, K., Hoskins, P., Klasa, R., Savage, K.J., Shenkier, T., Sutherland, J., et al. (2007) The Revised International Prognostic Index (R-IPI) Is a Better Predictor of Outcome than the Standard IPI for Patients with Diffuse Large B Cell Lymphoma Treated with R-CHOP. Blood, 109, 1857-1861. https://doi.org/10.1182/blood-2006-08-038257
[7]
Moskowitz, C. (2012) Diffuse Large B Cell Lymphoma: How Can We Cure More Patients in 2012? Best Practice & Research Clinical Haematology, 25, 41-47.
https://doi.org/10.1016/j.beha.2012.01.008
[8]
Labău, O. and Mutiu, G. (2010) BCL2 Family Related Genes Expression and Chemotherapy Response in Diffuse Large B-Cell Lymphoma. Annals of the Romanian Society for Cell Biology, 15, 71-76.
[9]
Yan, L.X., Liu, Y.H., Luo, D.L., Zhang, F., Cheng, Y., Luo, X.L., et al. (2014) 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, 9, 1-17. https://doi.org/10.1371/journal.pone.0104068
[10]
Reed, J.C. (1998) BCL-2 Family Proteins. Oncogene, 17, 3225-3236.
https://doi.org/10.1038/sj.onc.1202591
[11]
Dave, J., Campo, E., Iqbal, J., Neppalli, V.T., Wright, G., Dave, B.J., et al. (2006) BCL2 Expression Is a Prognostic Marker for the Activated B-Cell-Like Type of Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology.
https://www.researchgate.net/publication/7354933
[12]
Dunleavy, K. and Wilson, W.H. (2011) Differential Role of BCL2 in Molecular Subtypes of Diffuse Large B-Cell Lymphoma. Clinical Cancer Research, 17, 7505-7507.
https://doi.org/10.1158/1078-0432.CCR-11-2372
[13]
Tang, S.C., Visser, L., Hepperle, B., Hanson, J. and Poppema, S. (1994) Clinical Significance of BCL-2-MBR Gene Rearrangement and Protein Expression in Diffuse Large-Cell Non-Hodgkin’s Lymphoma: An Analysis of 83 Cases. Journal of Clinical Oncology, 12, 149-154. https://doi.org/10.1200/JCO.1994.12.1.149
[14]
Schraders, M., De Jong, D., Kluin, P., Groenen, P. and Van Krieken, H. (2005) Lack of BCL-2 Expression in Follicular Lymphoma May Be Caused by Mutations in the BCL2 Gene or by Absence of the T(14;18) Translocation. Journal of Pathology, 205, 329-335. https://doi.org/10.1002/path.1689
[15]
Swerdlow, S.H., Campo, E., Harris, N.L., et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. In: Bosman, F.T., Jaffe, E.S., Lakhani, S.R. and Ohgaki, H., Eds., World Health Organization Classification of Tumours, IARC, Lyon, France.
[16]
Wulfrank, D., Pauwels, C., Roels, H. and De Schryver, A. (1987) Extranodal Non-Hodgkin’s Lymphoma of the Head and Neck. Radiotherapy and Oncology, 8, 199-207.
https://doi.org/10.1016/S0167-8140(87)80243-8
[17]
Sohani, A.R. and Hasserjian, R.P. (2010) Diagnosis of Burkitt Lymphoma and Related Highgrad B-Cell Neoplasms. Surgical Pathology Clinics, 3, 1035-1059.
https://doi.org/10.1016/j.path.2010.09.010
[18]
Lossos, I.S., Czerwinski, D.K., Alizadeh, A.A., Wechser, M.A., Tibshirani, R., Botstein, D., et al. (2004) Prediction of Survival in Diffuse Large-B-Cell Lymphoma Based on the Expression of Six Genes. The New England Journal of Medicine, 350, 1828-1837. https://doi.org/10.1056/NEJMoa032520
[19]
Mounier, N., Briere, J., Gisselbrecht, C., Emile, J.-F., Lederlin, P., Sebban, C., et al. (2003) Rituximab plus CHOP (R-CHOP) Overcomes BCL-2-Associated Resistance to Chemotherapy in Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL).
https://doi.org/10.1182/blood-2002-11-3442
[20]
Maartense, E., Schuuring, P.M., Kluin, M.H.H., Kramer, J., Hermans, E., Wijburg, K., et al. (2011) Large B-Cell Lymphoma Clinical Relevance of BCL2, BCL6, and MYC Rearrangements in Diffuse.
[21]
Iqbal, J., Meyer, P.N., Smith, L.M., Johnson, N.A., Vose, J.M., Greiner, T.C., et al. (2011) BCL2 Predicts Survival in Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma Treated with CHOP-Like Therapy and Rituximab. Clinical Cancer Research, 17, 7785-7795. https://doi.org/10.1158/1078-0432.CCR-11-0267
[22]
Van Imhoff, G.W., Boerma, E.J.G., Van Der Holt, B., Schuuring, E., Verdonck, L.F., Kluin-Nelemans, H.C., et al. (2006) Prognostic Impact of Germinal Center-Associated Proteins and Chromosomal Breakpoints in Poor-Risk Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology, 24, 4135-4142.
https://doi.org/10.1200/JCO.2006.05.5897
[23]
Offit, K., lo Coco, F., Louie, D.C., Parsa, N.Z., Leung, D., Portlock, C., et al. (1994) Rearrangement of the BCL-6 Gene as a Prognostic Marker in Diffuse Large-Cell Lymphoma. The New England Journal of Medicine, 331, 74-80.
https://doi.org/10.1056/NEJM199407143310202
[24]
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, 322-332. https://doi.org/10.1046/j.1365-2141.2002.03435.x
[25]
Iqbal, J., Greiner, T.C., Patel, K., Dave, B.J., Smith, L., Ji, J., et al. (2007) Distinctive Patterns of BCL6 Molecular Alterations and Their Functional Consequences in Different Subgroups of Diffuse Large B-Cell Lymphoma. Leukemia, 21, 2332-2343.
https://doi.org/10.1038/sj.leu.2404856
[26]
Hans, C.P., Weisenburger, D.D., Greiner, T.C., Gascoyne, R.D., Delabie, J., Ott, G., et al. (2004) Confirmation of the Molecular Classification of Diffuse Large B-Cell Lymphoma by Immunohistochemistry Using a Tissue Microarray.
https://doi.org/10.1182/blood-2003-05-1545
[27]
Akay, O.M., Aras, B.D., Isiksoy, S., Toprak, C., Mutlu, F.S., Artan, S., et al. (2014) BCL2, BCL6, IGH, TP53, and MYC Protein Expression and Gene Rearrangements as Prognostic Markers in Diffuse Large B-Cell Lymphoma: A Study of 44 Turkish Patients. Cancer Genetics, 207, 87-93.
https://doi.org/10.1016/j.cancergen.2014.02.001
[28]
Veelken, H., Vik Dannheim, S., Schulte Moenting, J., Martens, U., Finke, J. and Schmitt-Graeff, A. (2007) Immunophenotype as Prognostic Factor for Diffuse Large B-Cell Lymphoma in Patients Undergoing Clinical Risk-Adapted Therapy. Annals of Oncology, 18, 931-939.
https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdm012
https://doi.org/10.1093/annonc/mdm012
[29]
Bubendorf, L., Sauter, G., Moch, H., Jordan, P., Blöchlinger, A., Gasser, T.C., et al. (1996) Prognostic Significance of BCL-2 in Clinically Localized Prostate Cancer. The American Journal of Pathology, 148, 1557-1565.
[30]
Hermine, O., Haioun, C., Lepage, E., d’Agay, M., Briere, J., Lavignac, C., et al. (1996) Prognostic Significance of BCL-2 Protein Expression in Aggressive Non-Hodgkin’s lymphoma. Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood, 87, 265-272.
https://doi.org/10.1182/blood.V87.1.265.265
[31]
Rashed, H., Abdelrahman, A.E., Ismail, E., Obaya, A. and Abdelhamid, M. (2017) Prognostic Significance of Double Expression of C-MYC and BCL2 in Diffuse Large B Cell Lymphoma. Clinical Lymphoma, Myeloma & Leukemia, 17, S360.
https://doi.org/10.1016/j.clml.2017.07.193
[32]
Lakshmaiah, K., Babu, K., Dasappa, L., Abraham, L., Suresh Babu, M., Premalatha, C., et al. (2017) BCL2 and Subtype as Prognostic and Predictive Markers of Diffuse Large B-Cell Lymphoma. Clinical Cancer Investigation Journal, 6, 103.
https://doi.org/10.4103/ccij.ccij_13_17
[33]
Rantanen, S., Monni, O., Joensuu, H., Franssila, K. and Knuutila, S. (2001) Causes and Consequences of BCL2 over Expression in Diffuse Large B-Cell Lymphoma. Leukemia & Lymphoma, 42, 1089-1098.
https://doi.org/10.3109/10428190109097729
[34]
van den Brand, M., Garcia-Garcia, M., Mathijssen, J.J.M., Colomo, L., Groenen, P.J.T.A., Serrano, S., et al. (2016) Partial Lack of BCL2 in Follicular Lymphoma: An Unusual Immunohistochemical Staining Pattern Explained by Ongoing BCL2 Mutation. Pathology, Research and Practice, 212, 148-150.
https://doi.org/10.1016/j.prp.2015.12.001
