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Distribution of Ki67 Proliferative Indices among WHO Subtypes of Non-Hodgkin's Lymphoma: Association with other Clinical Parameters

  • Hashmi, Atif Ali (Department of Histopathology, Liaquat National Hospital and Medical College) ;
  • Hussain, Zubaida Fida (Department of Histopathology, Liaquat National Hospital and Medical College) ;
  • Faridi, Naveen (Department of Histopathology, Liaquat National Hospital and Medical College) ;
  • Khurshid, Amna (Department of Histopathology, Liaquat National Hospital and Medical College)
  • 발행 : 2014.11.06

초록

Background: Non-hodgkin lymphoma (NHL) is a diverse group of disease encompassing divergent tumor types with contrasting clinical behaviors. We aimed to evaluate the usefulness of Ki67 index in segregating indolent from aggressive NHL and its association with clinical parameters. Materials and Methods: During a study period of 4.5 years, a total of 215 cases of lymphomas were diagnosed among of which 172 cases were NHL. Ki67 immunohistochemical staining was performed by the DAKO envision method. Average proportion of tumor cells stained was calculated to determine the proliferative index. Results: The mean age at diagnosis was 46.2 years +19.8 (3-81) with a male to female ratio of 1.5:1. Mean Ki67 index for indolent NHL included 23% for small cell, 25% for mantle cell, 28.5% for marginal zone and 34.6% for follicular lymphoma. On the other hand, mean Ki67 index for aggressive lymphomas were 66.4%, 66.9%, 80.3%, 83.3% and 94.4% for diffuse large B cell, T cell (NOS), anaplastic large cell, lymphoblastic and burkitts lymphoma respectively. No significant correlation was found between Ki67 index and other clinical parameters like age and extra nodal involvement. Conclusions: Ki67 index is a valuable IHC marker to distinguish indolent from aggressive lymphomas especially in small needle biopsies where exact typing may not be possible.

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참고문헌

  1. Akay OM, Aras BD, Isiksoy 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 Genet, 207, 87-93. https://doi.org/10.1016/j.cancergen.2014.02.001
  2. Ali AE, Morgen EK, Geddie WR et al (2010). Classifying B-cell non-Hodgkin lymphoma by using MIB-1 proliferative index in fine-needle aspirates. Cancer Cytopathol, 118, 166-72. https://doi.org/10.1002/cncy.20075
  3. Bellas C, Garcia D, Vicente Y et al (2014). Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-celllymphzoma. PLoS One, 9, e98169. https://doi.org/10.1371/journal.pone.0098169
  4. Bhurgri Y, Pervez S, Bhurgri A et al (2005). Increasing incidence of non-Hodgkin's lymphoma in Karachi, 1995-2002. Asian Pac J Cancer Prev, 6, 364-9.
  5. Broyde A, Boycov O, Strenov Y et al (2009). Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma. Am J Hematol, 84, 338-43. https://doi.org/10.1002/ajh.21406
  6. Broyde A, Boycov O, Strenov Y et al (2009). Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma. Am J Hematol, 84, 338-43. https://doi.org/10.1002/ajh.21406
  7. Cook JR, Goldman B, Tubbs RR et al (2014). Clinical significance of MYC expression and/or “high-grade” morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study. Am J Surg Pathol, 38, 494-501. https://doi.org/10.1097/PAS.0000000000000147
  8. Erlanson M, Casiano CA, Tan EM et al (1999). Immunohistochemical analysis of the proliferation associated nuclear antigen CENP-F in non-Hodgkin's lymphoma. Mod Pathol, 12, 69-74.
  9. Gaudio F, Giordano A, Perrone T et al (2011). High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab. Acta Haematol, 126, 44-51. https://doi.org/10.1159/000324206
  10. Gerdes J, Lemke H, Baisch H et al (1984). Cell cycle analysis of a cell proliferation- associated human nuclear antigen defined by monoclonal antibody Ki67. J Immunol, 133, 1710-1715
  11. Gerdes J, Schwab U, Lemke H, Stein H (1983). Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer, 31, 13-20 https://doi.org/10.1002/ijc.2910310104
  12. Gunia S, Kakies C, Erbersdobler A, Koch S, May M (2012). Scoring the percentage of Ki67 positive nuclei is superior to mitotic count and the mitosis marker phosphohistone H3 (PHH3) in terms of differentiating flat lesions of the bladder mucosa. J Clin Pathol, 65, 715-20. https://doi.org/10.1136/jclinpath-2011-200532
  13. Hadzi-Pecova L, Petrusevska G, Stojanovic A (2007). Non-Hodgkin's lymphomas: immunologic prognostic studies. Prilozi, 28, 39-55.
  14. Haroon S, Hashmi AA, Khurshid A et al (2013). Ki67 index in breast cancer: correlation with other prognostic markers and potential in Pakistani patients. Asian Pac J Cancer Prev, 14, 4353-8. https://doi.org/10.7314/APJCP.2013.14.7.4353
  15. He X, Chen Z, Fu T et al (2014). Ki-67 is a valuable prognostic predictor of lymphoma but its utility varies in lymphoma subtypes: evidence from a systematic meta-analysis. BMC Cancer, 14, 153. https://doi.org/10.1186/1471-2407-14-153
  16. Ishtiaq S, Hassan U, Mushtaq S, Akhtar N (2013). Determination of frequency of Epstein-Barr virus in non-Hodgkin lymphomas using EBV latent membrane protein 1 (EBVLMP1) immunohistochemical staining. Asian Pac J Cancer Prev, 14, 3963-7. https://doi.org/10.7314/APJCP.2013.14.6.3963
  17. Jerkeman M, Anderson H, Dictor M, Kvaloy S, Akerman M (2004). Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study. Ann Hematol, 83, 414-9. https://doi.org/10.1007/s00277-004-0855-x
  18. Jung SH, Yang DH, Ahn JS et al (2014). Serum lactate dehydrogenase with a systemic inflammation score is useful for predicting response and survival in patients with newly diagnosed diffuse large b-cell lymphoma. Acta Haematol, 133, 10-17.
  19. Kalogeraki A, Tzardi M, Panagiotides I et al (1997). MIB1 (Ki-67) expression in non-Hodgkin's lymphomas. Anticancer Res, 17, 487-491.
  20. Li J, Hu R, Liao AJ et al (2011). Ki-67 proliferative index in non-Hodgkin's lymphoma and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 19, 935-9.
  21. Li S, Feng X, Li T et al (2013). Extranodal NK/T-cell lymphoma, nasal type: a report of 73 cases at MD Anderson Cancer Center. Am J Surg Pathol, 14, 14-23.
  22. Martin AR, Weisenburger DD, Chan WC et al (1995). Prognostic value of cellular proliferation and histologic grade in follicular lymphoma. Blood, 85, 3671-8.
  23. Niikura N, Iwamoto T, Masuda S et al (2012). Immunohistochemical Ki67 labeling index has similar proliferation predictive power to various gene signatures in breast cancer. Cancer Sci, 103, 1508-12. https://doi.org/10.1111/j.1349-7006.2012.02319.x
  24. Petit B, Chaury MP, Le Clorennec C et al (2005).Indolent lymphoplasmacytic and marginal zone B-cell lymphomas: absence of both IRF4 and Ki67 expressionidentifies a better prognosis subgroup. Haematologica, 90, 200-6.
  25. Pinto AE, Cabecadas J, Nobrega SD, Mendonca E (2003). Flow cytometric S-phase fraction as a complementary biological parameter for the cytological grading of non-Hodgkin's lymphoma. Diagn Cytopathol, 29, 194-9. https://doi.org/10.1002/dc.10298
  26. Rabenhorst SH, Burini RC, Schmitt FC (1996). Proliferating cell nuclear antigen (PCNA) in non-Hodgkin's lymphomas: correlation with Working Formulation and Kiel classification in formalin-fixed paraffin-embedded material. Pathology, 28, 12-16. https://doi.org/10.1080/00313029600169423
  27. Rosenwald A, Wright G, Wiestner A et al (2003). The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survivalin mantle cell lymphoma. Cancer Cell, 3, 185-97. https://doi.org/10.1016/S1535-6108(03)00028-X
  28. Salek D, Vesela P, Boudova L et al (2014). Retrospective analysis of 235 unselected patients with mantle cell lymphoma confirms prognostic relevance of Mantle Cell Lymphoma International Prognostic Index and Ki-67 in the era of rituximab: long-term data from the Czech Lymphoma Project Database. Leuk Lymphoma, 55, 802-10. https://doi.org/10.3109/10428194.2013.815349
  29. Schaffel R, Hedvat CV, Teruya-Feldstein J et al (2010). Prognostic impact of proliferative index determined by quantitative image analysis and the InternationalPrognostic Index in patients with mantle cell lymphoma. Ann Oncol, 21, 133-9. https://doi.org/10.1093/annonc/mdp495
  30. Swerdlow SH, Camp E, Harris NL et al (2008). WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. In World Health Organization Classification of Tumors, 4th ed. Lyon: International Agency for Research.
  31. Vaidya R, Witzig TE (2014). Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann Oncol. pii: mdu109.
  32. Went P, Agostinelli C, Gallamini A, Piccaluga PP, Ascani S (2006). Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol, 24, 2472-9. https://doi.org/10.1200/JCO.2005.03.6327
  33. Wu L, Wang T, Gui W, Lin H, Xie K (2014). Prognostic Significance of Serum Beta-2 Microglobulin in Patients with Non-Hodgkin Lymphoma. Oncology, 87, 40-47. https://doi.org/10.1159/000362670
  34. Zekri AR, Hassan ZK, Bahnassy AA et al (2013). Gene expression profiling of non-hodgkin lymphomas. Asian Pac J Cancer Prev, 14, 4393-8. https://doi.org/10.7314/APJCP.2013.14.7.4393
  35. Zhang ZX, Shen CF, Zou WH et al (2013). Exploration of molecular mechanisms of diffuse large B-cell lymphoma development using a microarray. Asian Pac J Cancer Prev, 14, 929-34. https://doi.org/10.7314/APJCP.2013.14.2.929
  36. Zhou D, Xie WZ, Hu KY et al (2013). Prognostic values of various clinical factors and genetic subtypes for diffuse large B-cell lymphoma patients: a retrospective analysis of 227 cases. Asian Pac J Cancer Prev, 4, 929-34. https://doi.org/10.7314/APJCP.2013.14.2.929

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