Características inmunofenotípicas del linfoma difuso de células grandes B y expresión de la proteína C-MYC: experiencia en un centro de Ecuador
DOI:
https://doi.org/10.35509/01239015.58Palabras clave:
Linfoma de Células B Grandes Difuso, Centro germinal, Proteínas Proto-Oncogénicas c-myc, EcuadorResumen
Antecedentes: El linfoma difuso de células grandes B (LDCGB) constituye el 25 al 40% del total de los linfomas no Hodgkin (LNH) y es el subtipo histológico más frecuente en el mundo. En Ecuador el LDCGB corresponde al 49% del total de los casos de LNH, sin embargo no hay estudios de clasificación inmunofenotípica del LDCGB en centro germinal (CG) y no centro germinal (NCG). Este estudio se realizó para conocer el perfil inmunofenotípico del LDCGB en un hospital de Ecuador.
Métodos: Se recopiló del Servicio de Patología del Hospital Metropolitano de Quito, Ecuador, un total de 38 casos de LDCGB desde el 2006 al 2015, de los cuales 11 no cumplieron con los criterios de inclusión. La muestra final fue de 27 casos. Se realizaron microarreglos tisulares manuales para la aplicación de tres marcadores de inmunohistoquímica según el algoritmo de Hans (CD10, BCL6 y MUM1) y luego se correlacionó con la sobreexpresión de la proteína c-MYC.
Resultados: El 77,8% de casos fue tipo CG, 11,1% fue NCG y 11,1% fueron inclasificables según Hans.
Conclusiones: El subtipo de LDCGB más frecuente fue CG con 21 casos y de estos 40,7% sobreexpresaron c-MYC.
Biografía del autor/a
Johanna Cevallos, Hospital Metropolitano (Quito, Ecuador)
Laboratorio de Patología, Hospital Metropolitano, Quito, Ecuador
Nelson Montalvo, Hospital Metropolitano (Quito, Ecuador)
Laboratorio de Patología, Hospital Metropolitano, Quito, Ecuador
Referencias bibliográficas
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https://doi.org/10.1182/blood-2003-05-1545
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https://doi.org/10.1016/j.jfma.2016.09.006
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12. Castellanos OW. Acuerdo intraobservador en estudios de inmunohistoquímica para Linfoma B difuso de célula grande según protocolo de Hans [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2012.
13. Silva FC. Valor pronóstico do perfil inmunotípico em linfoma difuso de grandes células B [tese de Mestrado]. Porto (Portugal): Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto; 2010. p. 1-18. J. Cevallos et al.
14. Perry AM, Molina-Kirsch H, Nathwani BN, Diebold J, Maclennan KA, Müller-Hermelink HK, et al. Classification of non-Hodgkin lymphomas in Guatemala according to the World Health Organization system. Leuk Lymphoma. 2011;52(9):1681-8. 94.
https://doi.org/10.3109/10428194.2011.584254
15. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17):5494-502.
https://doi.org/10.1158/1078-0432.CCR-09-0113
16. Gupta M, Maurer MJ, Wellik LE, Law ME, Han JJ, Ozsan N, et al. Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP. Blood. 2012;120(22):4400-6.
https://doi.org/10.1182/blood-2012-05-428466
17. 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. ClinOncol. 2012;30(28):3452-9.
https://doi.org/10.1200/JCO.2011.41.0985
18. Kluk MJ, Chapuy B, Sinha P, Roy A, Dal Cin P, Neuberg DS, et al. Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas. PLoS One. 2012;7(4):e33813.
https://doi.org/10.1371/journal.pone.0033813
19. Batlle-López A, González de Villambrosía S, Francisco M, Malatxeberria S, Sáez A, Montalban C, et al. Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker. Oncotarget. 2016;7(14):18036-49.
https://doi.org/10.18632/oncotarget.7495
20. Duncavage E, Advani RH, Agosti S, Foulis P, Gibson C, Kang L, et al. Template for Reporting Results of Biomarker Testing of Specimens from patients with diffuse large B-cell lymphoma, not otherwise specified. Arch Pathol Lab Med. 2016;140(11):1225-17.
https://doi.org/10.5858/arpa.2015-0418-CP
21. Valentino C, Kendrick S, Johnson N, Gascoyne R, Chan WC, Weisenburger D, et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139(2):242-54.
https://doi.org/10.1309/AJCP2Z0TAGMUYJEB
22. 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(17):4173-83.
https://doi.org/10.1002/cncr.27396
23. 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(12):2253-63.
https://doi.org/10.1182/blood-2012-06-435842
24. Xu X, Zhang L, Wang Y, Zhang Q, Zhang L, Sun B, et al. Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review. Int J Clin Exp Pathol. 2013;6(4):788-94
25. Mahmoud AZ, George TI, Czuchlewski DR, Zhang QY, Wilson CS, Sever CE, et al. Scoring of MYC protein Expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists. Mod Pathol. 2015;28(4):545-51.
https://doi.org/10.1038/modpathol.2014.140
2. Ioachim H, Medeiros J. Nomenclature and classification of lymphomas. In: Ioachim ́s Lymph Node Pathology. 4th edition. Philadelphia: Wolters Kluwer; 2009. p. 296-305.
3. Cueva P, Yépez J. Sociedad de Lucha Contra el Cáncer/ Registro Nacional de Tumores. Epidemiología del cáncer en Quito 2006-2010. Quito; 2014. p. 152-62.
4. Stein H, Warnke RA, Chan WC, Jaffe ES, Chan JKC, Gatter KC et al. Diffuse large B-cell lymphoma, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IACR Press; 2008. p. 233-7.
5. O'Malley D, Grimm K, Banks P. Inmunohistology of Non- Hodgkin Lymphoma. In: Dabbs D. Diagnostic Inmunohistochemistry. Theranostic and Genomic applications. 4th edition. Elsevier Saunders; 2014. p.148- 16.
6. Young K, Medeiros LJ, Chan W. Diffuse Large B-cell Lymphoma. In: Orazi A, Weiss L, Foucar K, Knowles D. Knowles' Neoplastic Hematopathology. 3th edition. Philadelphia: Wolters Kluwer; 2014. p. 502-56
7. Grande C. Actualización en el tratamiento del linfoma difuso de células grandes B. En: Fernández- Rañada J, Alegre A (Eds). Cuadernos de Hematología. 2011;1-15.
8. Hans CP, Weisenberger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by inmunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
https://doi.org/10.1182/blood-2003-05-1545
9. ChenY, XiaoL,ZhuX,LuC,YuB,FanD,etal. Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China. Zhonghua Bing Li Xue Za Zhi. 2014;43(6):383-8.
10. 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 Formos Med Assoc. 2016;115(11):961-7.
https://doi.org/10.1016/j.jfma.2016.09.006
11. Ospina JA. Caracterización de los pacientes con diagnóstico de Linfoma B Difuso de células grande en el Instituto de Cancerología [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2015.
12. Castellanos OW. Acuerdo intraobservador en estudios de inmunohistoquímica para Linfoma B difuso de célula grande según protocolo de Hans [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2012.
13. Silva FC. Valor pronóstico do perfil inmunotípico em linfoma difuso de grandes células B [tese de Mestrado]. Porto (Portugal): Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto; 2010. p. 1-18. J. Cevallos et al.
14. Perry AM, Molina-Kirsch H, Nathwani BN, Diebold J, Maclennan KA, Müller-Hermelink HK, et al. Classification of non-Hodgkin lymphomas in Guatemala according to the World Health Organization system. Leuk Lymphoma. 2011;52(9):1681-8. 94.
https://doi.org/10.3109/10428194.2011.584254
15. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17):5494-502.
https://doi.org/10.1158/1078-0432.CCR-09-0113
16. Gupta M, Maurer MJ, Wellik LE, Law ME, Han JJ, Ozsan N, et al. Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP. Blood. 2012;120(22):4400-6.
https://doi.org/10.1182/blood-2012-05-428466
17. 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. ClinOncol. 2012;30(28):3452-9.
https://doi.org/10.1200/JCO.2011.41.0985
18. Kluk MJ, Chapuy B, Sinha P, Roy A, Dal Cin P, Neuberg DS, et al. Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas. PLoS One. 2012;7(4):e33813.
https://doi.org/10.1371/journal.pone.0033813
19. Batlle-López A, González de Villambrosía S, Francisco M, Malatxeberria S, Sáez A, Montalban C, et al. Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker. Oncotarget. 2016;7(14):18036-49.
https://doi.org/10.18632/oncotarget.7495
20. Duncavage E, Advani RH, Agosti S, Foulis P, Gibson C, Kang L, et al. Template for Reporting Results of Biomarker Testing of Specimens from patients with diffuse large B-cell lymphoma, not otherwise specified. Arch Pathol Lab Med. 2016;140(11):1225-17.
https://doi.org/10.5858/arpa.2015-0418-CP
21. Valentino C, Kendrick S, Johnson N, Gascoyne R, Chan WC, Weisenburger D, et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139(2):242-54.
https://doi.org/10.1309/AJCP2Z0TAGMUYJEB
22. 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(17):4173-83.
https://doi.org/10.1002/cncr.27396
23. 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(12):2253-63.
https://doi.org/10.1182/blood-2012-06-435842
24. Xu X, Zhang L, Wang Y, Zhang Q, Zhang L, Sun B, et al. Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review. Int J Clin Exp Pathol. 2013;6(4):788-94
25. Mahmoud AZ, George TI, Czuchlewski DR, Zhang QY, Wilson CS, Sever CE, et al. Scoring of MYC protein Expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists. Mod Pathol. 2015;28(4):545-51.
https://doi.org/10.1038/modpathol.2014.140
Cómo citar
[1]
Cevallos, J. y Montalvo, N. 2019. Características inmunofenotípicas del linfoma difuso de células grandes B y expresión de la proteína C-MYC: experiencia en un centro de Ecuador. Revista Colombiana de Cancerología. 23, 2 (jun. 2019), 41–44. DOI:https://doi.org/10.35509/01239015.58.
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25-06-2019
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