Objective: Hodgkin lymphoma (HL) is a hematological malignancy with a generally favorable prognosis, yet its pathogenesis remains unclear, and unknown risk factors affecting incidence and mortality are still being explored. This study aimed to assess the influence of diagnosis season and the presence of in situ hybridization (ISH) Epstein-Barr encoded RNA (EBER) on HL survival. Material and Methods: We evaluated 232 HL patients treated at Ege University Faculty of Medicine Hematology Clinic from January 1, 1994, to December 31, 2023. Results: Among the 232 patients (41.4% female and 58.6% male), the mean age at diagnosis was 38.42 years (SD: 15.99), with a median age of 35. The most common subtype was nodular sclerosing (47%), followed by mixed cellularity (29.3%) and nodular lymphocyte predominant (NLP) (9.9%). EBER was detected in 45.7% of patients, while 54.3% were EBER negative. The highest diagnosis rate occurred in winter (30.6%), and the lowest in spring (19.8%). EBER presence did not vary by season, and no significant difference in overall survival times was found between EBER positive and negative patients (p=0.427). Conclusion: Our findings indicate that EBER positivity does not significantly impact the prognosis of HL, with no seasonal variability in EBER rates. The lack of significant survival differences suggests that EBER has limited relevance in HL management. These insights contribute to the understanding of HL's clinical practice and pathogenesis, highlighting areas for future research.
Keywords: Hodgkin disease; Epstein-Barr virus encoded RNA; seasons
Amaç: Hodgkin lenfoma (HL), en iyi prognoza sahip hematolojik malignitelerden biridir. Bununla birlikte, HL'nin patogenezi tam olarak anlaşılmamış olup, HL insidansı ve mortalitesini etkileyebilecek potansiyel bilinmeyen risk faktörleri araştırılmaya devam etmektedir. Bu çalışmanın amacı, tanı mevsiminin ve in situ hibritizasyon (ISH) Epstein-Barr kodlu RNA (EBER) varlığının HL üzerindeki etkisini değerlendirmektir. Gereç ve Yöntemler: Bu çalışma, 1 Ocak 1994 ile 31 Aralık 2023 tarihleri arasında Ege Üniversitesi Tıp Fakültesi Hematoloji Kliniği'nde HL tanısı almış ve tedavi edilmiş 232 hastayı içermektedir. Bulgular: Bu çalışmada toplam 232 hasta (%41,4 kadın ve %58,6 erkek) değerlendirilmiştir. Tanı anındaki ortalama yaş 38,42 (SS: 15,99) olarak belirlenmiş, medyan yaş ise 35 bulunmuştur. HL'nin en yaygın alt tipi 47% ile nodüler sklerozan, ardından %29,3 ile karışık hücreli ve %9,9 ile nodüler lenfosit baskın (NLP) olarak saptanmıştır. EBER, hastaların %54,3'ünde yokken, %45,7'sinde tespit edilmiştir. En yüksek tanı oranı kış mevsiminde %30,6 olarak gözlemlenirken, en düşük oran bahar mevsiminde %19,8 olarak belirlenmiştir. EBER varlığı mevsimlere göre değişiklik göstermemiş ve EBER negatif ile pozitif hastalar arasında ortalama genel sağkalım sürelerinde istatistiksel olarak anlamlı bir fark bulunmamıştır (p=0,427). Sonuç: Çalışmamız, EBER pozitifliğinin Hodgkin Lenfoma (HL) prognozu üzerinde önemli bir etkisi olmadığını ortaya koymuştur. EBER pozitiflik oranları mevsimsel değişkenlik göstermemektedir. Bu bulgular, HL'nin klinik pratiği ve patogenezi hakkında önemli bilgiler sunmakta ve gelecekteki araştırmalar için yeni yönlerin belirlenmesine katkıda bulunmaktadır.
Anahtar Kelimeler: Hodgkin hastalığı; Epstein-Barr virus kodlanmış RNA; mevsimler
- Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. The World Health Organization classification of hematological malignancies report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997. Mod Pathol. 2000;13(2):193-207. [Crossref] [PubMed]
- Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361-92. [PubMed]
- Lynch HT, Marcus JN, Lynch JF. Genetics of Hodgkin's and non-Hodgkin's lymphoma: a review. Cancer Invest. 1992;10(3):247-56. [Crossref] [PubMed]
- Küppers R, Yahalom J, Josting A. Advances in biology, diagnostics, and treatment of Hodgkin's disease. Biol Blood Marrow Transplant. 2006;12(1 Suppl 1):66-76. [Crossref] [PubMed]
- Yung L, Linch D. Hodgkin's lymphoma. Lancet. 2003;361(9361):943-51. [Crossref] [PubMed]
- Urayama KY, Jarrett RF, Hjalgrim H, Diepstra A, Kamatani Y, Chabrier A, et al. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst. 2012;104(3):240-53. [Crossref] [PubMed] [PMC]
- Grufferman S, Cole P, Smith PG, Lukes RJ. Hodgkin's disease in siblings. N Engl J Med. 1977;296(5):248-50. [Crossref] [PubMed]
- Flerlage JE, Myers JR, Maciaszek JL, Oak N, Rashkin SR, Hui Y, et al. Discovery of novel predisposing coding and noncoding variants in familial Hodgkin lymphoma. Blood. 2023;141(11):1293-307. [Crossref] [PubMed] [PMC]
- Horwitz M, Wiernik PH. Pseudoautosomal linkage of Hodgkin disease. Am J Hum Genet. 1999;65(5):1413-22. [Crossref] [PubMed] [PMC]
- Mack TM, Cozen W, Shibata DK, Weiss LM, Nathwani BN, Hernandez AM, et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med. 1995;332(7):413-8. [Crossref] [PubMed]
- Minarovits J, Hu LF, Marcsek Z, Minarovits-Kormuta S, Klein G, Ernberg I. RNA polymerase III-transcribed EBER 1 and 2 transcription units are expressed and hypomethylated in the major Epstein-Barr virus-carrying cell types. J Gen Virol. 1992;73(Pt 7):1687-92. [PubMed]
- Clarke PA, Sharp NA, Clemens MJ. Expression of genes for the Epstein-Barr virus small RNAs EBER-1 and EBER-2 in Daudi Burkitt's lymphoma cells: effects of interferon treatment. J Gen Virol. 1992;73(Pt 12):3169-75. [Crossref] [PubMed]
- Allday MJ, Crawford DH, Griffin BE. Epstein-Barr virus latent gene expression during the initiation of B cell immortalization. J Gen Virol. 1989;70(Pt 7):1755-64. [PubMed]
- Howe JG, Steitz JA. Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proc Natl Acad Sci U S A. 1986;83(23):9006-10. [Crossref] [PubMed] [PMC]
- Schwemmle M, Clemens MJ, Hilse K, Pfeifer K, Tröster H, Müller WE, et al. Localization of Epstein-Barr virus-encoded RNAs EBER-1 and EBER-2 in interphase and mitotic Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1992;89(21):10292-6. [Crossref] [PubMed] [PMC]
- Clarke PA, Schwemmle M, Schickinger J, Hilse K, Clemens MJ. Binding of Epstein-Barr virus small RNA EBER-1 to the double-stranded RNA-activated protein kinase DAI. Nucleic Acids Res. 1991;19(2):243-8. [Crossref] [PubMed] [PMC]
- Clarke PA, Sharp NA, Arrand JR, Clemens MJ. Epstein-Barr virus gene expression in interferon-treated cells. Implications for the regulation of protein synthesis and the antiviral state. Biochim Biophys Acta. 1990;1050(1-3):167-73. [Crossref] [PubMed]
- Swaminathan S, Huneycutt BS, Reiss CS, Kieff E. Epstein-Barr virus-encoded small RNAs (EBERs) do not modulate interferon effects in infected lymphocytes. J Virol. 1992;66(8):5133-6. [Crossref] [PubMed] [PMC]
- Swaminathan S, Tomkinson B, Kieff E. Recombinant Epstein-Barr virus with small RNA (EBER) genes deleted transforms lymphocytes and replicates in vitro. Proc Natl Acad Sci U S A. 1991;88(4):1546-50. [Crossref] [PubMed] [PMC]
- Toczyski DP, Steitz JA. The cellular RNA-binding protein EAP recognizes a conserved stem-loop in the Epstein-Barr virus small RNA EBER 1. Mol Cell Biol. 1993;13(1):703-10. [PubMed] [PMC]
- Khan G, Coates PJ, Kangro HO, Slavin G. Epstein Barr virus (EBV) encoded small RNAs: targets for detection by in situ hybridisation with oligonucleotide probes. J Clin Pathol. 1992;45(7):616-20. [PubMed] [PMC]
- Hamilton-Dutoit SJ, Pallesen G. Detection of Epstein-Barr virus small RNAs in routine paraffin sections using non-isotopic RNA/RNA in situ hybridization. Histopathology. 1994;25(2):101-11. [PubMed]
- Niedobitek G, Herbst H. In situ detection of Epstein-Barr virus and phenotype determination of EBV-infected cells. Methods Mol Biol. 2006;326:115-37. [Crossref] [PubMed]
- Eliopoulos AG, Young LS. LMP1 structure and signal transduction. Semin Cancer Biol. 2001;11(6):435-44. [PubMed]
- Douglas S, Cortina-Borja M, Cartwright R. A quest for seasonality in presentation of leukaemia and non-Hodgkin's lymphoma. Leuk Lymphoma. 1999;32(5-6):523-32. [PubMed]
- Neilly IJ, Dawson AA, Bennett B, Douglas S. Evidence for a seasonal variation in the presentation of Hodgkins disease. Leuk Lymphoma. 1995;18(3-4):325-8. [Crossref] [PubMed]
- Chang ET, Blomqvist P, Lambe M. Seasonal variation in the diagnosis of Hodgkin lymphoma in Sweden. Int J Cancer. 2005;115(1):127-30. [PubMed]
- Székely E, Lindén O, Peterson S, Jerkeman M. Season of diagnosis is associated with overall survival in patients with diffuse large B-cell lymphoma but not with Hodgkin's lymphoma-A population-based Swedish Lymphoma Register study. Eur J Haematol. 2016;97(4):393-8. [Crossref] [PubMed]
- Porojnicu AC, Robsahm TE, Ree AH, Moan J. Season of diagnosis is a prognostic factor in Hodgkin's lymphoma: a possible role of sun-induced vitamin D. Br J Cancer. 2005;93(5):571-4. [Crossref] [PubMed] [PMC]
- Patır P, Eskin FE, Karakuş V, Kurtoğlu E. Is diagnostic season associated with hodgkin lymhoma survival? LLM journal. 2023;7(3):98-105. [Crossref]
- Hjalgrim H, Smedby KE, Rostgaard K, Molin D, Hamilton-Dutoit S, Chang ET, et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res. 2007;67(5):2382-8. [Crossref] [PubMed]
- Reiman A, Powell JE, Flavell KJ, Grundy RG, Mann JR, Parkes S, et al. Seasonal differences in the onset of the EBV-positive and-negative forms of paediatric Hodgkin's lymphoma. Br J Cancer. 2003;89(7):1200-1. [Crossref] [PubMed] [PMC]
- Parkes SE, Coad NA, Muir KR, Jones TJ, Cameron AH, Mann JR. Hodgkin's disease in children in the West Midlands, 1957-1986: a large population-based study. Pediatr Hematol Oncol. 1994;11(5):471-86. [Crossref] [PubMed]
- Armstrong AA, Shield L, Gallagher A, Jarrett RF. Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative Hodgkin's disease. Br J Cancer. 1998;77(7):1045-7. [Crossref] [PubMed] [PMC]
- Anagnostopoulos I, Hansmann ML, Franssila K, Harris M, Harris NL, Jaffe ES, et al. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood. 2000;96(5):1889-99. [PubMed]
.: Process List