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Hodgkin Lenfomada B Hücre Transkripsiyon Faktörlerinin İmmünohistokimyasal İfadesi ve Ayırıcı Tanıda Kullanımı

Yıl 2023, , 92 - 99, 31.01.2023
https://doi.org/10.16899/jcm.1224116

Öz

ÖZ
Amaç: Klasik Hodgkin Lenfoma sık görülmek ile birlikte ayrıcı tanısı zor olabilen lenfomalardandır. Hodgkin hücresinin germinal merkezli olabileceği düşünülmektedir. Bu çalışmadaki amacımız, Classic Hodgkin Lymphoma (CHL), Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) ve diffuse large B-cell lymphoma (DLBCL)’da germinal merkez transformasyon belirteçleri olan OCT-2, BOB.1, BCL-6, PAX-5, CD20 ve MUM-1’in ekspresyonlarını immünohistokimyasal yöntem ile, EBV early RNAs (EBER)’in chromogenic in-situ hybridization (ISH) ile değerlendirmektir.
Gereç ve yöntemler: 49 Hodgkin lenfoma (HL), 5'i NLPHL ve 19'u DLBCL tanılı biyopsi CD30, PAX-5, OCT-2, BOB.1, MUM-1, BCL-6 ve CD20 ve EBER pozitifliği açısından değerlendirildi. İstatistiksel analiz için SPSS 18 kullanıldı.
Bulgular: Çalışmaya %61.6 erkek ve %38.4 kadın olmak üzere 73 lenfoma olgusu dahil edildi. Hastaların medyan yaşı 50 idi. En sık görülen lenfoma tipi CHL (%67,1), en sık görülen alt tip mikst hücreli Hodgkin lenfoma (MSHL) idi. CHL ve DLBCL olguları arasında CD30, OCT-2, BOB.1, MUM-1, PAX-5, CD20, BCL-6, EBER ekspresyonu açısından istatistiksel olarak anlamlı fark vardı (p<0,001). Ek olarak BCL-6 ve EBER haricinde diğer tüm antikorlarda CHL ve NLPHL arasında istatistiki olarak anlamlı fark mevcuttu.
Sonuç: KHL'nin NLPHL ve DLBCL'den ayırıcı tanısında CD30, PAX-5, OCT-2, BOB.1, MUM-1, BCL-6 ve CD20 ve EBER'den oluşan bir panelin kullanılması çok faydalı olacaktır..

Kaynakça

  • 1. de Leval L, Jaffe ES. Lymphoma classification. The Cancer Journal. 2020;26(3):176-85.
  • 2. Swerdlow SH CE HN, Jaffe ES, Pileri SA, Stein H, Thit Rele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, Sieber. . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: International Agency for Research on Cancer 2017.
  • 3. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48.
  • 4. McCune RC, Syrbu SI, Vasef MA. Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB. 1, and PU. 1 in Hodgkin's and non-Hodgkin's lymphomas: a comparative study using high throughput tissue microarrays. Modern pathology. 2006;19(7):1010-8.
  • 5. Khan MR, Ahmad A, Kayani N, Minhas K. Expression of PAX-5 in B cell hodgkin and non hodgkin lymphoma. Asian Pacific Journal of Cancer Prevention: APJCP. 2018;19(12):3463.
  • 6. Torlakovic E, Tierens A, Dang HD, Delabie J. The transcription factor PU. 1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin’s disease. The American journal of pathology. 2001;159(5):1807-14.
  • 7. Browne P, Petrosyan K, Hernandez A, Chan JA. The B-cell transcription factors BSAP, Oct-2, and BOB.1 and the pan-B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. Am J Clin Pathol. 2003;120(5):767-77.
  • 8. O’Malley DP, Fedoriw Y, Weiss LM. Distinguishing classical Hodgkin lymphoma, gray zone lymphoma, and large B-cell lymphoma: a proposed scoring system. Applied Immunohistochemistry & Molecular Morphology. 2016;24(8):535-40.
  • 9. Watanabe T, Kitazawa R, Mizuno Y, Kuwahara N, Ito C, Sugita A, et al. BOB. 1-positive classical Hodgkin’s Lymphoma carries hypermethylation of its promoter as epigenetic marker of gene-silencing memory. Acta Histochemica et Cytochemica. 2014;47(3):125-31.
  • 10. O'Malley DP, Fedoriw Y, Weiss LM. Distinguishing Classical Hodgkin Lymphoma, Gray Zone Lymphoma, and Large B-cell Lymphoma: A Proposed Scoring System. Appl Immunohistochem Mol Morphol. 2016;24(8):535-40.
  • 11. García-Cosío M, Santón A, Martín P, Camarasa N, Montalbán C, García JF, et al. Analysis of transcription factor OCT. 1, OCT. 2 and BOB. 1 expression using tissue arrays in classical Hodgkin's lymphoma. Modern pathology. 2004;17(12):1531-8.
  • 12. Şeker M, Mengi A, Bilici A, Ustaalioğlu BB, Kefeli U, Özşeker NI, et al. Hodgkin lenfoma olgularının retrospektif değerlendirilmesi ve prognostik faktörlerin saptanması. Turkish Journal of Oncology/Türk Onkoloji Dergisi. 2011;26(3).
  • 13. Ferrarini I, Rigo A, Zamò A, Vinante F. Classical Hodgkin lymphoma cells may promote an IL-17-enriched microenvironment. Leukemia & lymphoma. 2019;60(14):3395-405.
  • 14. Khan MR, Ahmad A, Kayani N, Minhas K. Expression of PAX-5 in B Cell Hodgkin and Non Hodgkin Lymphoma. Asian Pac J Cancer Prev. 2018;19(12):3463-6.
  • 15. Theil J, Laumen H, Marafioti T, Hummel M, Lenz G, Wirth T, et al. Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood. 2001;97(10):3191-6.
  • 16. Latchman DS. The Oct-2 transcription factor. Int J Biochem Cell Biol. 1996;28(10):1081-3.
  • 17. Chang JF, Phillips K, Lundbäck T, Gstaiger M, Ladbury JE, Luisi B. Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding. J Mol Biol. 1999;288(5):941-52.
  • 18. Browne P, Petrosyan K, Hernandez A, Chan JA. The B-cell transcription factors BSAP, Oct-2, and BOB. 1 and the pan–B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. American journal of clinical pathology. 2003;120(5):767-77.
  • 19. Torlakovic E, Tierens A, Dang HD, Delabie J. The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease. Am J Pathol. 2001;159(5):1807-14.
  • 20. Torlakovic E, Torlakovic G, Nguyen PL, Brunning RD, Delabie J. The value of anti-pax-5 immunostaining in routinely fixed and paraffin-embedded sections: a novel pan pre-B and B-cell marker. Am J Surg Pathol. 2002;26(10):1343-50.
  • 21. Abukhiran I, Syrbu SI, Holman CJ. Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin. Am J Clin Pathol. 2021;156(3):409-26.
  • 22. Zhang Y, Wang H, Ren C, Yu H, Fang W, Zhang N, et al. Correlation Between C-MYC, BCL-2, and BCL-6 Protein Expression and Gene Translocation as Biomarkers in Diagnosis and Prognosis of Diffuse Large B-cell Lymphoma. Front Pharmacol. 2018;9:1497.
  • 23. Uherova P, Valdez R, Ross CW, Schnitzer B, Finn WG. Nodular lymphocyte predominant Hodgkin lymphoma. An immunophenotypic reappraisal based on a single-institution experience. Am J Clin Pathol. 2003;119(2):192-8.
  • 24. Fromm JR, Thomas A, Wood BL. Characterization and Purification of Neoplastic Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma from Lymph Nodes by Flow Cytometry and Flow Cytometric Cell Sorting. Am J Pathol. 2017;187(2):304-17.
  • 25. Carbone A, Gloghini A, Gaidano G, Franceschi S, Capello D, Drexler HG, et al. Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease. Blood, The Journal of the American Society of Hematology. 1998;92(7):2220-8.
  • 26. Carbone A, Gloghini A, Aldinucci D, Gattei V, Dalla-Favera R, Gaidano G. Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease. Br J Haematol. 2002;117(2):366-72.
  • 27. Huang W, Xie J, Xu X, Gao X, Xie P, Zhou X. MUM-1 expression differentiates AITL with HRS-like cells from cHL. Int J Clin Exp Pathol. 2015;8(9):11372-8.
  • 28. Irawan C, Iskandar M, Harahap AS, Rumende CM, Ham MF. MUM1 Expression versus Hans Algorithm to Predict Prognosis in Indonesian Diffuse Large B-Cell Lymphoma Patients Receiving R-CHOP. Cancer Manag Res. 2022;14:925-35.
  • 29. Xu ML, Gabali A, Hsi ED, Fedoriw Y, Vij K, Salama ME, et al. Practical Approaches on CD30 Detection and Reporting in Lymphoma Diagnosis. Am J Surg Pathol. 2020;44(2):e1-e14.
  • 30. Hoeller S, Zihler D, Zlobec I, Obermann EC, Pileri SA, Dirnhofer S, et al. BOB.1, CD79a and cyclin E are the most appropriate markers to discriminate classical Hodgkin's lymphoma from primary mediastinal large B-cell lymphoma. Histopathology. 2010;56(2):217-28.
  • 31. Nam-Cha SH, Montes-Moreno S, Salcedo MT, Sanjuan J, Garcia JF, Piris MA. Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers. Mod Pathol. 2009;22(8):1006-15.
  • 32. Eichenauer DA, Engert A. Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management. Hematology Am Soc Hematol Educ Program. 2017;2017(1):324-8.
  • 33. O'Malley DP, Dogan A, Fedoriw Y, Medeiros LJ, Ok CY, Salama ME. American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma. Ann Diagn Pathol. 2019;39:105-10.
  • 34. Gulen G, ÖZCAN MA, ÖZKAL S. EBER In Situ Hybridization Experience In Hodgkin Lymphoma. Journal of Basic and Clinical Health Sciences. 2021;5(3):201-4.
  • 35. ÇOKBANKİR Ö. Diffüz büyük b hücreli lenfomalarda sitogenetik olarak alt tiplerin ve bunların prognostik özelliklerinin araştırılması: Dokuz Eylül Üniversitesi Tıp Fakültesi; 2013.

Immunohistochemical Expression of B Cell Transcription Factors in Hodgkin’s Lymphoma and Their Use in Differential Diagnosis

Yıl 2023, , 92 - 99, 31.01.2023
https://doi.org/10.16899/jcm.1224116

Öz

Aim: Classical Hodgkin lymphoma is common, it is one of the lymphomas whose differential diagnosis can be difficult. It is thought that Hodgkin cell may originate from the germinal center. Our aim in this study was to determine the germinal center transformation markers OCT-2, BOB.1, BCL-6, PAX-5, CD20 and MUM-1 in Classic Hodgkin Lymphoma (CHL), Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Diffuse Large B-cell Lymphoma (DLBCL) to evaluate the expressions of by immunohistochemical method and chromogenic in-situ hybridization (ISH) of EBV early RNAs (EBER).
Material and methods: 49 biopsies diagnosed with Hodgkin lymphoma (HL), 5 with NLPHL and 19 with DLBCL were evaluated for CD30, PAX-5, OCT-2, BOB.1, MUM-1, BCL-6, and CD20, and EBER positivity. SPSS 18 was used for statistical analysis.
Results: 73 lymphoma cases were included in the study, 61.6% males and 38.4% females. The median age of patients was 50 years. CHL (67.1%) was the most common lymphoma type, and mixed cellular Hodgkin lymphoma (MSHL) was the most common subtype. There was a statistically significant difference in CD30, OCT-2, BOB.1, MUM-1, PAX-5, CD20, BCL-6, EBER expression between CHL and DLBCL cases (p<0,001). In addition, there was a statistically significant difference between CHL and NLPHL for all antibodies except BCL-6 and EBER.
Conclusion: It would be very helpful to use a panel consisting of CD30, PAX-5, OCT-2, BOB.1, MUM-1, BCL-6, and CD20, and EBER in the differential diagnosis of CHL from NLPHL and DLBCL.

Kaynakça

  • 1. de Leval L, Jaffe ES. Lymphoma classification. The Cancer Journal. 2020;26(3):176-85.
  • 2. Swerdlow SH CE HN, Jaffe ES, Pileri SA, Stein H, Thit Rele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, Sieber. . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: International Agency for Research on Cancer 2017.
  • 3. Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720-48.
  • 4. McCune RC, Syrbu SI, Vasef MA. Expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB. 1, and PU. 1 in Hodgkin's and non-Hodgkin's lymphomas: a comparative study using high throughput tissue microarrays. Modern pathology. 2006;19(7):1010-8.
  • 5. Khan MR, Ahmad A, Kayani N, Minhas K. Expression of PAX-5 in B cell hodgkin and non hodgkin lymphoma. Asian Pacific Journal of Cancer Prevention: APJCP. 2018;19(12):3463.
  • 6. Torlakovic E, Tierens A, Dang HD, Delabie J. The transcription factor PU. 1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin’s disease. The American journal of pathology. 2001;159(5):1807-14.
  • 7. Browne P, Petrosyan K, Hernandez A, Chan JA. The B-cell transcription factors BSAP, Oct-2, and BOB.1 and the pan-B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. Am J Clin Pathol. 2003;120(5):767-77.
  • 8. O’Malley DP, Fedoriw Y, Weiss LM. Distinguishing classical Hodgkin lymphoma, gray zone lymphoma, and large B-cell lymphoma: a proposed scoring system. Applied Immunohistochemistry & Molecular Morphology. 2016;24(8):535-40.
  • 9. Watanabe T, Kitazawa R, Mizuno Y, Kuwahara N, Ito C, Sugita A, et al. BOB. 1-positive classical Hodgkin’s Lymphoma carries hypermethylation of its promoter as epigenetic marker of gene-silencing memory. Acta Histochemica et Cytochemica. 2014;47(3):125-31.
  • 10. O'Malley DP, Fedoriw Y, Weiss LM. Distinguishing Classical Hodgkin Lymphoma, Gray Zone Lymphoma, and Large B-cell Lymphoma: A Proposed Scoring System. Appl Immunohistochem Mol Morphol. 2016;24(8):535-40.
  • 11. García-Cosío M, Santón A, Martín P, Camarasa N, Montalbán C, García JF, et al. Analysis of transcription factor OCT. 1, OCT. 2 and BOB. 1 expression using tissue arrays in classical Hodgkin's lymphoma. Modern pathology. 2004;17(12):1531-8.
  • 12. Şeker M, Mengi A, Bilici A, Ustaalioğlu BB, Kefeli U, Özşeker NI, et al. Hodgkin lenfoma olgularının retrospektif değerlendirilmesi ve prognostik faktörlerin saptanması. Turkish Journal of Oncology/Türk Onkoloji Dergisi. 2011;26(3).
  • 13. Ferrarini I, Rigo A, Zamò A, Vinante F. Classical Hodgkin lymphoma cells may promote an IL-17-enriched microenvironment. Leukemia & lymphoma. 2019;60(14):3395-405.
  • 14. Khan MR, Ahmad A, Kayani N, Minhas K. Expression of PAX-5 in B Cell Hodgkin and Non Hodgkin Lymphoma. Asian Pac J Cancer Prev. 2018;19(12):3463-6.
  • 15. Theil J, Laumen H, Marafioti T, Hummel M, Lenz G, Wirth T, et al. Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood. 2001;97(10):3191-6.
  • 16. Latchman DS. The Oct-2 transcription factor. Int J Biochem Cell Biol. 1996;28(10):1081-3.
  • 17. Chang JF, Phillips K, Lundbäck T, Gstaiger M, Ladbury JE, Luisi B. Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding. J Mol Biol. 1999;288(5):941-52.
  • 18. Browne P, Petrosyan K, Hernandez A, Chan JA. The B-cell transcription factors BSAP, Oct-2, and BOB. 1 and the pan–B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. American journal of clinical pathology. 2003;120(5):767-77.
  • 19. Torlakovic E, Tierens A, Dang HD, Delabie J. The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease. Am J Pathol. 2001;159(5):1807-14.
  • 20. Torlakovic E, Torlakovic G, Nguyen PL, Brunning RD, Delabie J. The value of anti-pax-5 immunostaining in routinely fixed and paraffin-embedded sections: a novel pan pre-B and B-cell marker. Am J Surg Pathol. 2002;26(10):1343-50.
  • 21. Abukhiran I, Syrbu SI, Holman CJ. Markers of Follicular Helper T Cells Are Occasionally Expressed in T-Cell or Histiocyte-Rich Large B-Cell Lymphoma, Classic Hodgkin Lymphoma, and Atypical Paracortical HyperplasiaA Diagnostic Pitfall For T-Cell Lymphomas of T Follicular Helper Origin. Am J Clin Pathol. 2021;156(3):409-26.
  • 22. Zhang Y, Wang H, Ren C, Yu H, Fang W, Zhang N, et al. Correlation Between C-MYC, BCL-2, and BCL-6 Protein Expression and Gene Translocation as Biomarkers in Diagnosis and Prognosis of Diffuse Large B-cell Lymphoma. Front Pharmacol. 2018;9:1497.
  • 23. Uherova P, Valdez R, Ross CW, Schnitzer B, Finn WG. Nodular lymphocyte predominant Hodgkin lymphoma. An immunophenotypic reappraisal based on a single-institution experience. Am J Clin Pathol. 2003;119(2):192-8.
  • 24. Fromm JR, Thomas A, Wood BL. Characterization and Purification of Neoplastic Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma from Lymph Nodes by Flow Cytometry and Flow Cytometric Cell Sorting. Am J Pathol. 2017;187(2):304-17.
  • 25. Carbone A, Gloghini A, Gaidano G, Franceschi S, Capello D, Drexler HG, et al. Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease. Blood, The Journal of the American Society of Hematology. 1998;92(7):2220-8.
  • 26. Carbone A, Gloghini A, Aldinucci D, Gattei V, Dalla-Favera R, Gaidano G. Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin's disease. Br J Haematol. 2002;117(2):366-72.
  • 27. Huang W, Xie J, Xu X, Gao X, Xie P, Zhou X. MUM-1 expression differentiates AITL with HRS-like cells from cHL. Int J Clin Exp Pathol. 2015;8(9):11372-8.
  • 28. Irawan C, Iskandar M, Harahap AS, Rumende CM, Ham MF. MUM1 Expression versus Hans Algorithm to Predict Prognosis in Indonesian Diffuse Large B-Cell Lymphoma Patients Receiving R-CHOP. Cancer Manag Res. 2022;14:925-35.
  • 29. Xu ML, Gabali A, Hsi ED, Fedoriw Y, Vij K, Salama ME, et al. Practical Approaches on CD30 Detection and Reporting in Lymphoma Diagnosis. Am J Surg Pathol. 2020;44(2):e1-e14.
  • 30. Hoeller S, Zihler D, Zlobec I, Obermann EC, Pileri SA, Dirnhofer S, et al. BOB.1, CD79a and cyclin E are the most appropriate markers to discriminate classical Hodgkin's lymphoma from primary mediastinal large B-cell lymphoma. Histopathology. 2010;56(2):217-28.
  • 31. Nam-Cha SH, Montes-Moreno S, Salcedo MT, Sanjuan J, Garcia JF, Piris MA. Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers. Mod Pathol. 2009;22(8):1006-15.
  • 32. Eichenauer DA, Engert A. Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management. Hematology Am Soc Hematol Educ Program. 2017;2017(1):324-8.
  • 33. O'Malley DP, Dogan A, Fedoriw Y, Medeiros LJ, Ok CY, Salama ME. American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma. Ann Diagn Pathol. 2019;39:105-10.
  • 34. Gulen G, ÖZCAN MA, ÖZKAL S. EBER In Situ Hybridization Experience In Hodgkin Lymphoma. Journal of Basic and Clinical Health Sciences. 2021;5(3):201-4.
  • 35. ÇOKBANKİR Ö. Diffüz büyük b hücreli lenfomalarda sitogenetik olarak alt tiplerin ve bunların prognostik özelliklerinin araştırılması: Dokuz Eylül Üniversitesi Tıp Fakültesi; 2013.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Orjinal Araştırma
Yazarlar

Çiğdem Özdemir 0000-0001-8500-0744

Filiz Yavaşoğlu 0000-0002-4017-4668

Yiğit Şenol 0000-0002-2220-4595

Yayımlanma Tarihi 31 Ocak 2023
Kabul Tarihi 30 Ocak 2023
Yayımlandığı Sayı Yıl 2023

Kaynak Göster

AMA Özdemir Ç, Yavaşoğlu F, Şenol Y. Immunohistochemical Expression of B Cell Transcription Factors in Hodgkin’s Lymphoma and Their Use in Differential Diagnosis. J Contemp Med. Ocak 2023;13(1):92-99. doi:10.16899/jcm.1224116