Inutility of IMP3 Marker in Differentiating Hodgkin Lymphoma from Large Cell Lymphoma
Abstract
Background: Hodgkin’s lymphoma is one of the most commonly diagnosed lymphomas in Western society. Today Reed-Sternberg cells are identified by positive staining of several biomarkers. The IMP3 (insulin-like growth factor II m-RNA-binding protein 3) marker is a member of the insulin-like growth factor II mRNA binding protein family that has been suggested as a diagnostic marker in some epithelial malignancies. In this study, we aimed to evaluate the expression profile of IMP3 in Hodgkin’s lymphoma patients and compare it with those with large cell lymphoma. Methods: In this study, patients diagnosed with Hodgkin’s lymphoma between 2016 and 2018 were recruited. For the control group, patients diagnosed with large cell lymphoma were chosen. Paraffin blocks were collected and cut by a microtome machine. Immunohistochemical staining was performed on the slides for the IMP3 marker, using the Envision method. The color intensity was divided into four groups, and data on age, gender, staining intensity, sampling rate, and staining pattern entered at the end of the checklists. The collected data were analyzed using SPSS 19 software. The paired t-test has was employed, and a significant statistical level of 0.05 was considered in all tests. Results: In this study, 145 patients in a wide range of 5 to 84 years (the mean age = 41 ± 17 years) were studied. Fifty-three patients were diagnosed with diffuse large B-cell lymphoma (36.6%), 4 cases (2.8%) with anaplastic large cell lymphoma and 88 cases with (60.7%) Hodgkin’s lymphoma. Among 145 patients in the current study, 143 patients (98.6%) were positive for IMP3. IMP3 was positive in all patients with Hodgkin’s lymphoma and anaplastic large cell lymphoma, and only 2 cases of diffuse large B-cell lymphoma were negative for this maker, in whom severe necrosis was noted. Consequently, there is not a vivid difference between Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (p-value=0.153) Conclusion: The marker is positive for Hodgkin’s lymphoma with a negative background and may be used as a supplementary marker along with CD15 and CD30 to detect neoplastic cells. However, it cannot help differentiate it from large cell lymphomas because it is also positive for non-Hodgkin lymphomas.
1. Ioachim HL, Medeiros LJ. Ioachim's lymph node pathology: Lippincott Williams & Wilkins; 2009.
2. Stein H, Hummel M, editors. Cellular origin and clonality of classic Hodgkin's lymphoma: immunophenotypic and molecular studies. Seminars in hematology; 1999.
3. 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.
4. Hummel M, Ziemann K, Lammert H, Pileri S, Sabattini E, Stein H. Hodgkin's disease with monoclonal and polyclonal populations of Reed–Sternberg cells. New England Journal of Medicine. 1995;333(14):901-6.
5. Küppers R, Rajewsky K. The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annual review of immunology. 1998;16(1):471-93.
6. Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, et al. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues 4th Ed.(2008). 2008.
7. Chu W-S, Abbondanzo SL, Frizzera G. Inconsistency of the immunophenotype of Reed-Sternberg cells in simultaneous and consecutive specimens from the same patients. A paraffin section evaluation in 56 patients. The American journal of pathology. 1992;141(1):11.
8. Vasef MA, Alsabeh R, Jeffrey Medeiros L, Weiss LM. Immunophenotype of Reed-Sternberg and Hodgkin’s cells in sequential biopsy specimens of Hodgkin’s disease: a paraffin-section immunohistochemical study using the heat-induced epitope retrieval method. American journal of clinical pathology. 1997;108(1):54-9.
9. Horne G, Medlicott SA, Mansoor A, Lategan J, Lai R, Beck P. A definitive diagnosis of primary Hodgkin lymphoma on endoscopic biopsy material utilizing in-depth immunohistochemical analysis. Canadian Journal of Gastroenterology and Hepatology. 2007;21(3):185-8.
10. Desouki MM, Post GR, Cherry D, Lazarchick J. PAX-5: a valuable immunohistochemical marker in the differential diagnosis of lymphoid neoplasms. Clinical medicine & research. 2010;8(2):84-8.
11. Herbeck R, Teodorescu Brînzeu D, Giubelan M, Lazăr E, Dema A, Ioniţă H. B-cell transcription factors Pax-5, Oct-2, BOB. 1, Bcl-6, and MUM1 are useful markers for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. Rom J Morphol Embryol. 2011;52(1):69-74.
12. Metzger ML, Howard SC, Hudson MM, Gow KW, Li CS, Krasin MJ, et al. Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma. Pediatric blood & cancer. 2006;46(3):314-9.
13. Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Molecular and cellular biology. 1999;19(2):1262-70.
14. Mueller-Pillasch F, Lacher U, Wallrapp C, Micha A, Zimmerhackl F, Hameister H, et al. Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene. 1997;14(22):2729-33.
15. Mueller-Pillasch F, Pohl B, Wilda M, Lacher U, Beil M, Wallrapp C, et al. Expression of the highly conserved RNA binding protein KOC in embryogenesis. Mechanisms of development. 1999;88(1):95-9.
16. Lu D, Vohra P, Chu PG, Woda B, Rock KL, Jiang Z. An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia. The American journal of surgical pathology. 2009;33(4):521-5.
17. Wachter DL, Kristiansen G, Soll C, Hellerbrand C, Breuhahn K, Fritzsche F, et al. Insulin‐like growth factor II mRNA‐binding protein 3 (IMP3) expression in hepatocellular carcinoma. A clinicopathological analysis with emphasis on diagnostic value. Histopathology. 2012;60(2):278-86.
18. Vranic S, Gurjeva O, Frkovic-Grazio S, Palazzo J, Tawfik O, Gatalica Z. IMP3, a proposed novel basal phenotype marker, is commonly overexpressed in adenoid cystic carcinomas but not in apocrine carcinomas of the breast. Applied Immunohistochemistry & Molecular Morphology. 2011;19(5):413-6.
19. Shi M, Fraire AE, Chu P, Cornejo K, Woda BA, Dresser K, et al. Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation. The American journal of surgical pathology. 2011;35(6):878-82.
20. Li H-G, Han J-J, Huang Z-Q, Wang L, Chen W-L, Shen X-M. IMP3 is a novel biomarker to predict metastasis and prognosis of tongue squamous cell carcinoma. Journal of Craniofacial Surgery. 2011;22(6):2022-5.
21. Walter O, Prasad M, Lu S, Quinlan RM, Edmiston KL, Khan A. IMP3 is a novel biomarker for triple negative invasive mammary carcinoma associated with a more aggressive phenotype. Human pathology. 2009;40(11):1528-33.
22. Li D, Yan D, Tang H, Zhou C, Fan J, Li S, et al. IMP3 is a novel prognostic marker that correlates with colon cancer progression and pathogenesis. Annals of surgical oncology. 2009;16(12):3499-506.
23. Ikenberg K, Fritzsche FR, Zuerrer-Haerdi U, Hofmann I, Hermanns T, Seifert H, et al. Insulin-like growth factor II mRNA binding protein 3 (IMP3) is overexpressed in prostate cancer and correlates with higher Gleason scores. BMC cancer. 2010;10(1):341.
24. McGowan P, Nelles N, Wimmer J, Williams D, Wen J, Li M, et al. Differentiating between Burkitt lymphoma and CD10+ diffuse large B-cell lymphoma: the role of commonly used flow cytometry cell markers and the application of a multiparameter scoring system. American journal of clinical pathology. 2012;137(4):665-70.
25. Tang H, Wei Q, Ge J, Jian W, Liu J, Zhong L, et al. IMP3 as a supplemental diagnostic marker for Hodgkin lymphoma. Human pathology. 2013;44(10):2167-72.
26. Ansell SM, editor Hodgkin lymphoma: diagnosis and treatment. Mayo Clinic Proceedings; 2015: Elsevier.
27. Copeland A, Younes A. Current treatment strategies in Hodgkin lymphomas. Current opinion in oncology. 2012;24(5):466-74.
28. Garcia J, Mollejo M, Fraga M, Forteza J, Muniesa J, Pérez‐Guillermo M, et al. Large B‐cell lymphoma with Hodgkin's features. Histopathology. 2005;47(1):101-10.
29. Shooshtarizadeh T, Nazeri A, Zare-Mirzaie A, Movahedinia S. Expression of insulin-like growth factor ІI mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma. Pathology-Research and Practice. 2016;212(4):335-9.
30. Vercellini P, Cribiù FM, Del Gobbo A, Carcangiu ML, Somigliana E, Bòsari S. The oncofetal protein IMP3: a novel biomarker and triage tool for premalignant atypical endometriotic lesions. Fertility and sterility. 2013;99(7):1974-9.
31. Burdelski C, Jakani-Karimi N, Jacobsen F, Möller-Koop C, Minner S, Simon R, et al. IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8,877 human cancers and normal tissues. Oncology reports. 2018;39(1):3-12.
32. Gong Y, Woda BA, Jiang Z. Oncofetal protein IMP3, a new cancer biomarker. Advances in anatomic pathology. 2014;21(3):191-200.
33. Radfar F, Achak F, Rajaei F. The relationship between IMP3 expression in colorectal adenocarcinoma and clinicopathologic findings. Journal of Biotechnology and Health Science. 2015.
34. King RL, Pasha T, Roullet MR, Zhang PJ, Bagg A. IMP-3 is differentially expressed in normal and neoplastic lymphoid tissue. Human pathology. 2009;40(12):1699-705.
35. Hartmann EM, Beà S, Navarro A, Trapp V, Campo E, Ott G, et al. Increased tumor cell proliferation in mantle cell lymphoma is associated with elevated insulin-like growth factor 2 mRNA-binding protein 3 expression. Modern Pathology. 2012;25(9):1227.
36. Pinkus GS, Pinkus JL, Langhoff E, Matsumura F, Yamashiro S, Mosialos G, et al. Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin's disease. Evidence for a dendritic or B cell derivation? The American journal of pathology. 1997;150(2):543.
37. Masoud R, Ibrahiem A, Tantawy D, Eldosoky I. The complementary role of insulin-like growth factor II mRNA-binding protein 3 (IMP3) in diagnosis of Hodgkin's lymphoma. Annals of diagnostic pathology. 2019;42:64-8.
2. Stein H, Hummel M, editors. Cellular origin and clonality of classic Hodgkin's lymphoma: immunophenotypic and molecular studies. Seminars in hematology; 1999.
3. 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.
4. Hummel M, Ziemann K, Lammert H, Pileri S, Sabattini E, Stein H. Hodgkin's disease with monoclonal and polyclonal populations of Reed–Sternberg cells. New England Journal of Medicine. 1995;333(14):901-6.
5. Küppers R, Rajewsky K. The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annual review of immunology. 1998;16(1):471-93.
6. Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, et al. WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues 4th Ed.(2008). 2008.
7. Chu W-S, Abbondanzo SL, Frizzera G. Inconsistency of the immunophenotype of Reed-Sternberg cells in simultaneous and consecutive specimens from the same patients. A paraffin section evaluation in 56 patients. The American journal of pathology. 1992;141(1):11.
8. Vasef MA, Alsabeh R, Jeffrey Medeiros L, Weiss LM. Immunophenotype of Reed-Sternberg and Hodgkin’s cells in sequential biopsy specimens of Hodgkin’s disease: a paraffin-section immunohistochemical study using the heat-induced epitope retrieval method. American journal of clinical pathology. 1997;108(1):54-9.
9. Horne G, Medlicott SA, Mansoor A, Lategan J, Lai R, Beck P. A definitive diagnosis of primary Hodgkin lymphoma on endoscopic biopsy material utilizing in-depth immunohistochemical analysis. Canadian Journal of Gastroenterology and Hepatology. 2007;21(3):185-8.
10. Desouki MM, Post GR, Cherry D, Lazarchick J. PAX-5: a valuable immunohistochemical marker in the differential diagnosis of lymphoid neoplasms. Clinical medicine & research. 2010;8(2):84-8.
11. Herbeck R, Teodorescu Brînzeu D, Giubelan M, Lazăr E, Dema A, Ioniţă H. B-cell transcription factors Pax-5, Oct-2, BOB. 1, Bcl-6, and MUM1 are useful markers for the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma. Rom J Morphol Embryol. 2011;52(1):69-74.
12. Metzger ML, Howard SC, Hudson MM, Gow KW, Li CS, Krasin MJ, et al. Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma. Pediatric blood & cancer. 2006;46(3):314-9.
13. Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Molecular and cellular biology. 1999;19(2):1262-70.
14. Mueller-Pillasch F, Lacher U, Wallrapp C, Micha A, Zimmerhackl F, Hameister H, et al. Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene. 1997;14(22):2729-33.
15. Mueller-Pillasch F, Pohl B, Wilda M, Lacher U, Beil M, Wallrapp C, et al. Expression of the highly conserved RNA binding protein KOC in embryogenesis. Mechanisms of development. 1999;88(1):95-9.
16. Lu D, Vohra P, Chu PG, Woda B, Rock KL, Jiang Z. An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia. The American journal of surgical pathology. 2009;33(4):521-5.
17. Wachter DL, Kristiansen G, Soll C, Hellerbrand C, Breuhahn K, Fritzsche F, et al. Insulin‐like growth factor II mRNA‐binding protein 3 (IMP3) expression in hepatocellular carcinoma. A clinicopathological analysis with emphasis on diagnostic value. Histopathology. 2012;60(2):278-86.
18. Vranic S, Gurjeva O, Frkovic-Grazio S, Palazzo J, Tawfik O, Gatalica Z. IMP3, a proposed novel basal phenotype marker, is commonly overexpressed in adenoid cystic carcinomas but not in apocrine carcinomas of the breast. Applied Immunohistochemistry & Molecular Morphology. 2011;19(5):413-6.
19. Shi M, Fraire AE, Chu P, Cornejo K, Woda BA, Dresser K, et al. Oncofetal protein IMP3, a new diagnostic biomarker to distinguish malignant mesothelioma from reactive mesothelial proliferation. The American journal of surgical pathology. 2011;35(6):878-82.
20. Li H-G, Han J-J, Huang Z-Q, Wang L, Chen W-L, Shen X-M. IMP3 is a novel biomarker to predict metastasis and prognosis of tongue squamous cell carcinoma. Journal of Craniofacial Surgery. 2011;22(6):2022-5.
21. Walter O, Prasad M, Lu S, Quinlan RM, Edmiston KL, Khan A. IMP3 is a novel biomarker for triple negative invasive mammary carcinoma associated with a more aggressive phenotype. Human pathology. 2009;40(11):1528-33.
22. Li D, Yan D, Tang H, Zhou C, Fan J, Li S, et al. IMP3 is a novel prognostic marker that correlates with colon cancer progression and pathogenesis. Annals of surgical oncology. 2009;16(12):3499-506.
23. Ikenberg K, Fritzsche FR, Zuerrer-Haerdi U, Hofmann I, Hermanns T, Seifert H, et al. Insulin-like growth factor II mRNA binding protein 3 (IMP3) is overexpressed in prostate cancer and correlates with higher Gleason scores. BMC cancer. 2010;10(1):341.
24. McGowan P, Nelles N, Wimmer J, Williams D, Wen J, Li M, et al. Differentiating between Burkitt lymphoma and CD10+ diffuse large B-cell lymphoma: the role of commonly used flow cytometry cell markers and the application of a multiparameter scoring system. American journal of clinical pathology. 2012;137(4):665-70.
25. Tang H, Wei Q, Ge J, Jian W, Liu J, Zhong L, et al. IMP3 as a supplemental diagnostic marker for Hodgkin lymphoma. Human pathology. 2013;44(10):2167-72.
26. Ansell SM, editor Hodgkin lymphoma: diagnosis and treatment. Mayo Clinic Proceedings; 2015: Elsevier.
27. Copeland A, Younes A. Current treatment strategies in Hodgkin lymphomas. Current opinion in oncology. 2012;24(5):466-74.
28. Garcia J, Mollejo M, Fraga M, Forteza J, Muniesa J, Pérez‐Guillermo M, et al. Large B‐cell lymphoma with Hodgkin's features. Histopathology. 2005;47(1):101-10.
29. Shooshtarizadeh T, Nazeri A, Zare-Mirzaie A, Movahedinia S. Expression of insulin-like growth factor ІI mRNA binding protein 3 (IMP3) in enchondroma and chondrosarcoma. Pathology-Research and Practice. 2016;212(4):335-9.
30. Vercellini P, Cribiù FM, Del Gobbo A, Carcangiu ML, Somigliana E, Bòsari S. The oncofetal protein IMP3: a novel biomarker and triage tool for premalignant atypical endometriotic lesions. Fertility and sterility. 2013;99(7):1974-9.
31. Burdelski C, Jakani-Karimi N, Jacobsen F, Möller-Koop C, Minner S, Simon R, et al. IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8,877 human cancers and normal tissues. Oncology reports. 2018;39(1):3-12.
32. Gong Y, Woda BA, Jiang Z. Oncofetal protein IMP3, a new cancer biomarker. Advances in anatomic pathology. 2014;21(3):191-200.
33. Radfar F, Achak F, Rajaei F. The relationship between IMP3 expression in colorectal adenocarcinoma and clinicopathologic findings. Journal of Biotechnology and Health Science. 2015.
34. King RL, Pasha T, Roullet MR, Zhang PJ, Bagg A. IMP-3 is differentially expressed in normal and neoplastic lymphoid tissue. Human pathology. 2009;40(12):1699-705.
35. Hartmann EM, Beà S, Navarro A, Trapp V, Campo E, Ott G, et al. Increased tumor cell proliferation in mantle cell lymphoma is associated with elevated insulin-like growth factor 2 mRNA-binding protein 3 expression. Modern Pathology. 2012;25(9):1227.
36. Pinkus GS, Pinkus JL, Langhoff E, Matsumura F, Yamashiro S, Mosialos G, et al. Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin's disease. Evidence for a dendritic or B cell derivation? The American journal of pathology. 1997;150(2):543.
37. Masoud R, Ibrahiem A, Tantawy D, Eldosoky I. The complementary role of insulin-like growth factor II mRNA-binding protein 3 (IMP3) in diagnosis of Hodgkin's lymphoma. Annals of diagnostic pathology. 2019;42:64-8.
| Files | ||
| Issue | Vol 12 No 1 (2020) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v12i1.5730 | |
| Keywords | ||
| Hodgkin’s Lymphoma Non - Hodgkin’s Lymphoma IMP3 CD15 CD30 | ||
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How to Cite
1.
Zare Mehrjerdi A, Ahmadi M. Inutility of IMP3 Marker in Differentiating Hodgkin Lymphoma from Large Cell Lymphoma. Basic Clin Cancer Res. 2020;12(1):18-25.
