Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Prognostic Sub-Grouping of Diffuse Large B-Cell Lymphomas into Germinal Centre And Post Germinal Centre Groups by Immunohistochemistry after 6 Cycles of Chemotherapy

  • Hassan, Usman (Department of Histopathology, Armed Forces Institute of Pathology) ;
  • Mushtaq, Sajid (Department of Histopathology, Armed Forces Institute of Pathology) ;
  • Mamoon, Nadira (Department of Histopathology, Armed Forces Institute of Pathology) ;
  • Asghar, Asghar Hussain (Department of Histopathology, Armed Forces Institute of Pathology) ;
  • Ishtiaq, Sheeba (Department of Histopathology, Armed Forces Institute of Pathology)
  • Published : 2012.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Introduction: Diffuse large B-cell lymphomas (DLBCL) can be divided into germinal centre (GC-DLBCL) and post germinal centre (post GC-DLBCL) groups by applying immunohistochemical antibodies. As these subgroups respond differently to chemotherapy, it is possible at diagnosis to select a poor prognostic subgroup for aggressive treatment. Objective: To determine the frequencies of GC-DLBCL and post GC-DLBCL in patients by immunohistochemistry (IHC) and the clinical response after six cycles of chemotherapy. Subjects and Methods: In this descriptive study conducted in AFIP and CMH, Rawalpindi and NORI, Islamabad, from September 2010 to September 2011, a total of 75 pretreatment cases of DLBCL diagnosed during the study period were included. Cases were segregated in to GC-DLBCL and post GC-DLBCL groups according to results of immunohistochemistry markers CD10, BCL6 and MUM1. Immediate clinical response was assessed after 6 cycles of chemotherapy. Response was divided into complete response, partial response, stable disease or relapse or progression. Results: The mean age was $54.2{\pm}15$. Males were 53 (70.7%). Forty (53.3%) cases comprised the GC-DLBCL group; 25(62.5%) of them showed a complete response. Most patients of the post GC-DLBCL 19(54%) showed relapse/progression. Results of immediate clinical response in both prognostic subgroups were significant (p<0.05). Results regarding positivity with immunohistochemical antibodies CD10 (p 0.011), BCL6 (p 0.013) and MUM1 (p 0.000) regarding immediate clinical response were also significant. Conclusion: GC-DLBCL group shows better response to CHOP chemotherapy regimen. Immunohistochemistry should be used to further classify DLBCL as this can enable us to select aggressive group for aggressive treatment. This manuscript is important because the study is the first to becarried out exclusively in Pakistan or our part of the world.

Keywords

References

  1. Abbasi AN, Zahid S, Karsan F, Ali N, Bhurgri Y (2010). Lymphoma cases referred to the radiation oncology service of a tertiary referral university hospital in Karachi, Pakistan: a retrospective study. Asian Pac J Cancer Prev, 11, 107-10.
  2. Aftab K, Bhurgri Y, Pervez S (2006). Small B cell Non-Hodgkins Lymphoma in Pakistan. J Pak Med Assoc, 56, 22-5.
  3. Borovecki A, Korac P, Nola M, Ivankovic D, Jaksic B, Dominis M (2008). Prognostic significance of B-cell differentiation genes encoding proteins in diffuse large B-cell lymphoma and follicular lymphoma grade 3. Croat Med J, 49, 625-35. https://doi.org/10.3325/cmj.2008.5.625
  4. Cheson BD (2008). New staging and response criteria for non- Hodgkin lymphoma and Hodgkin lymphoma. Radiol Clin North Am, 46, 213-23. https://doi.org/10.1016/j.rcl.2008.03.003
  5. Cheson BD, Pfistner B, Juweid ME, et al (2007). Revised response criteria for malignant lymphoma. J Clin Oncol, 25, 579-86. https://doi.org/10.1200/JCO.2006.09.2403
  6. Choi WW, Weisenburger DD, Greiner TC, et al (2009). A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res, 15, 5494-502. https://doi.org/10.1158/1078-0432.CCR-09-0113
  7. De Jong D, Xie W, Rosenwald A, et al (2009). Immunohistochemical prognostic markers in diffuse large B-cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications (a study from the Lunenburg Lymphoma Biomarker Consortium). J Clin Pathol, 62, 128-38. https://doi.org/10.1136/jcp.2008.057257
  8. Fu K, Weisenburger DD, Choi WW, et al (2008). Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol, 26, 4587-94. https://doi.org/10.1200/JCO.2007.15.9277
  9. Haarer CF, Roberts RA, Frutiger YM, Grogan TM, Rimsza LM (2006). Immunohistochemical classification of de Novo, transformed, and relapsed diffuse large B-Cell lymphoma into germinal center B-Cell and nongerminal center B-Cell subtypes correlates with gene expression profile and patient survival. Arch Pathol Lab Med, 130, 1819-24.
  10. Ilic I, Mitrovic Z, Aurer I, et al (2009). Lack of prognostic significance of the germinal-center phenotype in diffuse large B-cell lymphoma patients treated with CHOP-like chemotherapy with and without rituximab. Int J Hematol, 90, 74-80. https://doi.org/10.1007/s12185-009-0353-y
  11. Jaffe ES, Harris NL, Stein H, Isaacson PG (2008). Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood, 112, 4384-99. https://doi.org/10.1182/blood-2008-07-077982
  12. Jamal S, Moghal S, Mamoon N, (2006). The pattern of malignant tumours: tumour registry data analysis, AFIP, Rawalpindi, Pakistan (1992-2001). J Pak Med Assoc, 56, 359-62.
  13. Karin ES (2006). Epidemiology and etiology of non-Hodgkin lymphoma - a review. Acta Oncologica, 45, 258-271. https://doi.org/10.1080/02841860500531682
  14. Lossos IS, Morgensztern D (2006). Prognostic biomarkers in diffuse large B-cell lymphoma. J Clin Oncol, 24, 995-1007. https://doi.org/10.1200/JCO.2005.02.4786
  15. Malumbres R, Chen J, Tibshirani R, et al (2008). Paraffinbased 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Blood, 111, 5509-14. https://doi.org/10.1182/blood-2008-02-136374
  16. Muris JJ, Meijer CJ, Vos W, et al (2006). Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol, 208, 714-23. https://doi.org/10.1002/path.1924
  17. Mushtaq S, Akhtar N, Jamal S, et al (2008). Malignant lymphomas in Pakistan according to the WHO classification of lymphoid neoplasms. Asian Pac J Cancer Prev, 9, 229-32.
  18. Oh YH, Park CK (2006). Prognostic evaluation of nodal diffuse large B cell lymphoma by immunohistochemical profiles with emphasis on CD138 expression as a poor prognostic factor. J Korean Med Sci, 21, 397-405. https://doi.org/10.3346/jkms.2006.21.3.397
  19. Rimsza LM, Leblanc ML, Unger JM, et al (2008). Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. Blood, 112, 3425-33. https://doi.org/10.1182/blood-2008-02-137372
  20. Saad AA, Awed NM, Abdel-Hafeez ZM, et al (2010). Prognostic value of immunohistochemical classification of diffuse large B-cell lymphoma into germinal center B-cell and nongerminal center B-cell subtypes. Saudi Med J, 31, 135-41.
  21. Sehn LH, Berry B, Chhanabhai M, 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, 1857-61. https://doi.org/10.1182/blood-2006-08-038257
  22. Seki R, Ohshima K, Fujisaki T, et al (2009). Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. Cancer Sci, 100, 1842-7. https://doi.org/10.1111/j.1349-7006.2009.01268.x
  23. Sjo LD, Poulsen CB, Hansen M, Moller MB, Ralfkiaer E (2007). Profiling of diffuse large B-cell lymphoma by immunohistochemistry: identification of prognostic subgroups. Eur J Haematol, 79, 501-7. https://doi.org/10.1111/j.1600-0609.2007.00976.x
  24. Veelken H, Vik Dannheim S, Schulte Moenting J, et al (2007). Immunophenotype as prognostic factor for diffuse large B-cell lymphoma in patients undergoing clinical risk-adapted therapy. Ann Oncol, 18, 931-9. https://doi.org/10.1093/annonc/mdm012
  25. Wagner SD, Amen F, Trivedi PS, et al (2007). Bcl-6 and c-Myc are rarely co-expressed in adult diffuse large B-cell lymphoma. Leuk Lymphoma, 48, 1510-3. https://doi.org/10.1080/10428190701458491
  26. Winter JN, Weller EA, Horning SJ, et al (2006). Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood, 107, 4207-13. https://doi.org/10.1182/blood-2005-10-4222
  27. Xu JZ, Guo Z, Zhang M, Li X, Li YJ, Rao SQ (2006). Peeling off the hidden genetic heterogeneities of cancers based on disease-relevant functional modules. Mol Med, 12, 25-33.
  28. Zaja F, Tomadini V, Zaccaria A, et al (2006). CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma, 47, 2174-80. https://doi.org/10.1080/10428190600799946

Cited by

  1. Prognostic Values of Various Clinical Factors and Genetic Subtypes for Diffuse Large B-cell lymphoma Patients: A Retrospective Analysis of 227 Cases vol.14, pp.2, 2013, https://doi.org/10.7314/APJCP.2013.14.2.929
  2. SLE and Non-Hodgkin’s Lymphoma: A Case Series and Review of the Literature vol.2017, pp.2090-6897, 2017, https://doi.org/10.1155/2017/1658473