Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.727
Index Copernicus  – 166.39
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 6, November-December, p. 1149–1155

doi: 10.17219/acem/61427

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Angiogenesis in CD5-positive Diffuse Large B Cell Lymphoma: A Morphometric Analysis

Nina Woźnialis1,A,B,C,D, Beata Gierej1,2,B,C,E, Lidia Popławska3,B, Mateusz Ziarkiewicz4,B,D, Ewa Wolińska2,B,C, Elżbieta Kulczycka1,B, Bogna Ziarkiewicz-Wróblewska1,2,A,C,E,F

1 Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute and Oncology Center, Warszawa, Poland

2 Department of Pathology, Center for Biostructure Research, Medical University of Warsaw, Poland

3 Department of Lymphoid Malignancies, Maria Sklodowska-Curie Institute and Oncology Center, Poland

4 Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Poland

Abstract

Background. CD5-positive diffuse large B cell lymphoma (DLBCL) is the least frequent immunohistochemical subgroup of DLBCL. The relatively little available data suggests a worse outcome in this population, resulting from a resistance to chemotherapy.
Objectives. The aim was the comparative assessment of angiogenesis in both CD5-positive and CD5-negative DLBCL, as well as in lymphatic tissues without lymphoproliferative diseases.
Material and Methods. The analysis included 36 cases of CD5-positive DLBCL (19 females and 17 males) aged 29–87 years (mean age 69), diagnosed and treated in the Maria Sklodowska-Curie Institute and Oncology Center and Medical University of Warsaw in 2002−2013. The control group comprised 28 cases of CD5-negative DLBCL (14 females and 14 males) aged 24–82 years (mean age 58.5). The secondary control group (13 cases) consisted of normal lymphatic tissue obtained from patients without lymphoproliferative diseases. The level of angiogenesis was assessed on the basis of immunohistochemical CD34, vWF and HIF1α expression measured using morphometric methods.
Results. CD5-positive DLBCL, in comparison to CD5-negative DLBCL, was characterized by: (1) higher mean of total blood vessel area, (2) higher mean total ratio of blood vessel area and staining intensity, (3) higher mean of total blood vessel area in regions defined as hot spots, (4) higher mean of total ratio of blood vessel area and staining intensity in hot spots. The measurements in lymph nodes without lymphoproliferative diseases lay between the values obtained in both DLBCL subgroups.
Conclusion. We observed a significant exacerbation of angiogenesis in CD5-positive DLBCL in comparison to the CD5-negative subgroup, possibly explaining its more aggressive clinical course. Our data does not substantiate the hypothesis that angiogenesis is more pronounced in frequent CD5-negative DLBCL subgroup in comparison to benign lymphatic tissue.

Key words

CD5-positive DLBCL, angiogenesis, CD34, vWF, HIF1α

References (29)

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed., IARC Press, Lyon 2008, 9−15.
  2. Niitsu N, Okamoto M, Tamaru J, Yoshino T, Nakamura N, Nakamura S, Ohshima K, Nakamine H, Hirano M: Clinicopathologic characteristics and treatment outcome of the addition of rituximab to chemotherapy for CD5- -positive in comparison with CD5-negative diffuse large B-cell lymphoma. Ann Oncol 2010, 21, 2069−2074.
  3. Dvorak HF: Angiogenesis: Update 2005. J Thromb Haemost 2005, 3, 24−28.
  4. Cao Y, Langer R: A review of Judah Folkman’s remarkable achievements in biomedicine. Proc Natl Acad Sci USA 2008, 105, 13203−13205.
  5. Carmeliet P: Angiogenesis in health and disease. Nat Med 2003, 9, 653−660.
  6. Ferrara N: Vascular endothelial growth factor: Basic science and clinical progress. Endocr Rev 2004, 25, 581−611.
  7. Jain P, Fayad LE, Rosenwald A, Young KH, O’Brien S: Recent advances in de novo CD5+ diffuse large B cell lymphoma. Am J Hematol 2013, 88, 798−802.
  8. Cardesa-Salzmann TM, Colomo L, Gutierrez G, Chan WC, Weisenburger D, Climent F, Gonzalez-Barca E, Mercadal S, Arenillas L, Serrano S, Tubbs R, Delabie J, Gascoyne RD, Connors JM, Mate JL, Rimsza L, Braziel R, Rosenwald A, Lenz G, Wright G, Jaffe ES, Staudt L, Jares P, Lopez-Guillermo A, Campo E: High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy. Haematologica 2011, 96, 996−1001.
  9. Vacca A, Ribatti D, Ruco L, Giacchetta F, Nico B, Quondamatteo F, Ria R, Iurlaro M, Dammacco F: Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Br J Cancer 1999, 79, 965−970.
  10. Arias V, Soares FA: Vascular density (tumor angiogenesis) in non-Hodgkin’s lymphomas and florid follicular hyperplasia: A morphometric study. Leuk Lymph 2000, 40, 157−166.
  11. Crivellato E, Nico B, Vacca A, Ribatti D: B-cell non-Hodgkin’s lymphomas express heterogeneous patterns of neovascularization. Hematologica 2003, 88, 671−678.
  12. Ribatti D, Vacca A, Marzullo A, Nico B, Ria R, Roncali L, Dammacco F: Angiogenesis and mast cell density with tryptase activity increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Int J Cancer 2000, 85, 171−175.
  13. Ridell B, Norrby K: Intratumoral microvascular density in malignant lymphomas of B-cell origin. APMIS 2001, 109, 66−72.
  14. Kadowaki I, Ichinohasama R, Harigae H, Ishizawa K, Okitsu Y, Kameoka J, Sasaki T: Accelerated lymphangiogenesis in malignant lymphoma: Possible role of VEGF-A and VEGF-C. Br Journal Haematol 2005, 130, 869−877.
  15. Korkolopoulou P, Thymara I, Kavantzas N, Vassilakopoulos TP, Angelopoulou MK, Kokoris SI, Dimitriadou EM, Siakantaris MP, Anargyrou K, Panayiotidis P, Tsenga A, Androulaki A, DoussisAnagnostopoulou IA, Patsouris E, Pangalis GA: Angiogenesis in Hodgkin’s lymphoma: A morphometric approach in 286 patients with prognostic implications. Leukemia 2005, 19, 894−900.
  16. Mazur G, Wróbel T, Dzięgiel P, Jeleń M, Kuliczkowski K, Zabel M: Angiogenesis measured by expression of CD34 antigen in lymph nodes of patients with non-Hodgkin’s lymphomas. Folia Histochem Cytobiol 2004, 42, 241−243.
  17. Vacca A, Ribatti D, Ruco L, Giacchetta F, Nico B, Quondamatteo F, Ria R, Iurlaro M, Dammacco F: Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Br J Cancer 1999, 79, 965−970.
  18. Ribatti D, Vacca A, Nico B, Fanelli M, Roncali L, Dammacco F: Angiogenesis spectrum in the stroma of B-cell non-Hodgkin’s lymphomas. An immunohistochemical and ultrastructural study. Eur J Haematol 1996, 56, 45−53.
  19. Wołowiec D: Angiogeneza i limfangiogeneza w chłoniakach złośliwych nieziarniczych. Acta Haematol Pol 2011, 42, 357−365 [in Polish].
  20. Gryczyński M, Pietruszewska W: Angiogeneza jako nowy czynnik rokowniczy u chorych na raka krtani. Otorynolaryngologia 2002, 1, 13−20 [in Polish].
  21. Hewiston KS, Schofield CJ: The HIF pathway as a therapeutic target. Drug Discovery Today 2004, 9, 704−710.
  22. Hockel M, Vaupel P: Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects. JNCI 2001, 93, 266−276.
  23. Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE: Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc Natl Acad Sci USA 1991, 88, 5680−5684.
  24. Gasińska A, Biesaga B: Dwa oblicza hipoksji nowotworów. Nowotwory 2010, 60, 332−340 [in Polish].
  25. Maxwell PH: The HIF pathway in cancer. Sem Cell Dev Biol 2005, 16, 523−530.
  26. Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A: Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1 alfa. Genes Dev 2000, 1, 34−44.
  27. Rimassa L, Santoro A: Sorafenib therapy in advanced hepatocellular carcinoma: The SHARP trial. Exp Rev Anticancer Ther 2009, 9, 739−745.
  28. Olbryt M, Szala S: Białkowe inhibitory angiogenezy w terapii nowotworów. Współcz Onkol 2005, 9, 48−53 [in Polish].
  29. Kopic E, Cickusic E, Kopic A, Arnautovic-Custovic A, Halilbasic A, Tinjic L, Hasic S, Simendic V: Morphometric angiogenesis parameters for indolent and aggressive non-Hodgkin’s lymphoma. Med Arh 2011, 65, 9−12.