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CC BY-NC-ND 4.0 · J Lab Physicians 2023; 15(02): 282-288
DOI: 10.1055/s-0042-1760400
Original Article

Histopathological Evaluation of Angiogenic Markers in Non-Hodgkin's Lymphoma

Priyanka Singh
1   Department of Pathology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
,
Anita Tahlan
2   Department of Pathology, Government Medical College and Hospital, Chandigarh, India
3   Department of Medicine, Government Medical College and Hospital, Chandigarh, India
,
Harsh Mohan
2   Department of Pathology, Government Medical College and Hospital, Chandigarh, India
,
Ram Singh
2   Department of Pathology, Government Medical College and Hospital, Chandigarh, India
3   Department of Medicine, Government Medical College and Hospital, Chandigarh, India
› Author Affiliations Funding None.
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Abstract

Background Angiogenesis plays a key role in the development, maintenance, and progression of tumor. The incidence of non-Hodgkin's lymphoma (NHL) is increasing from the past three decades.

Materials and Methods The aim of the study is to evaluate microvessel density (MVD) using CD34 monoclonal antibody and vascular endothelial growth factor (VEGF) using monoclonal antibody that were studied in pretreatment paraffin-embedded tissue samples of 60 cases.

Results MVD was found to be increased in parallel with increasing grade of tumor. B-NHL had a mean MVD of 79.5 ± 8.8 (no./mm2), while T-NHL had a mean MVD of 183 ± 37.6 (no./mm2). VEGF expression was seen in 42 cases (70%), 20 cases (33.3%) showed strong VEGF expression, and the remainder showed either weak (36.6%) or no (30%) staining. Strong VEGF expression is seen in 100% cases of T-NHL and 77.7% cases of B-NHL. Mean MVD and VEGF expression was found to be correlated significantly with the histological grade of NHL (p = 0.001 and p = 0.000, respectively). Average microvessel counts were 53, 82.9, and 130.8 vessels (no./mm2) for negative, weak, and strong VEGF staining, respectively. These differences were statistically significant (p = 0.005 for strong vs. negative and p = 0.091 for strong vs. weak VEGF staining individually).

Conclusion As the grade of tumor progresses, the angiogenic potential also advances which seems to depend on VEGF. The presence of higher MVD in high-grade lymphomas can be utilized for antiangiogenic drugs.

Keywords

angiogenesis - CD34 - hot spots - microvessel density - non-Hodgkin's lymphoma


Publication History

Article published online:
18 January 2023

© 2023. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Ekström-Smedby K. Epidemiology and etiology of non-Hodgkin lymphoma–a review. Acta Oncol 2006; 45 (03) 258-271
    CrossrefPubMedGoogle Scholar
  • 2 American Cancer Society Detailed Guide: non-Hodgkin lymphoma. Accessed October 14, 2014, at: http://www.cancer.org/acs/groups/cid/document/webcontent/003126pdf.pdf
    Google Scholar
  • 3 Müller AMS, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-Hodgkin's lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol 2005; 84 (01) 1-12
    CrossrefPubMedGoogle Scholar
  • 4 Zahra Mozaheb. (2012). Epidemiology of Lymphoid Malignancy in Asia, Epidemiology Insights, Dr. Maria De Lourdes Ribeiro De Souza Da Cunha (Ed.), ISBN: 978-953-51-0565-7, InTech, Available from: http://www.intechopen.com/books/epidemiology-insights/epidemiology-of-lymphoid-malignancy-in-asia
  • 5 National Cancer Institute. Adult non-Hodgkin lymphoma treatment: cellular classification of adult non-Hodgkin lymphoma. Accessed October 14, 2014, at: http://www.cancer.gov/cancertopics/pdq/treatment/adult-nonhodgkins/HealthProfessional/page2
    Google Scholar
  • 6 Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002; 29 (6, suppl 16): 15-18
    CrossrefPubMedGoogle Scholar
  • 7 Alshenawy HA. Prognostic significance of vascular endothelial growth factor, basic fibroblastic growth factor, and microvessel density and their relation to cell proliferation in B-cell non-Hodgkin's lymphoma. Ann Diagn Pathol 2010; 14 (05) 321-327
    CrossrefPubMedGoogle Scholar
  • 8 Ruan J, Hajjar K, Rafii S, Leonard JP. Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma. Ann Oncol 2009; 20 (03) 413-424
    CrossrefPubMedGoogle Scholar
  • 9 Kopic E, Cickusic E, Kopic A. et al. Morphometric angiogenesis parameters for indolent and aggressive non-Hodgkin's lymphoma. Med Arh 2011; 65 (01) 9-12
    Google Scholar
  • 10 Gratzinger D, Zhao S, Marinelli RJ. et al. Microvessel density and expression of vascular endothelial growth factor and its receptors in diffuse large B-cell lymphoma subtypes. Am J Pathol 2007; 170 (04) 1362-1369
    CrossrefPubMedGoogle Scholar
  • 11 Skarin AT, Dorfman DM. Non-Hodgkin's lymphomas: current classification and management. CA Cancer J Clin 1997; 47 (06) 351-372
    CrossrefPubMedGoogle Scholar
  • 12 Eltom MA, Jemal A, Mbulaiteye SM, Devesa SS, Biggar RJ. Trends in Kaposi's sarcoma and non-Hodgkin's lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst 2002; 94 (16) 1204-1210
    CrossrefPubMedGoogle Scholar
  • 13 Groves FD, Linet MS, Travis LB, Devesa SS. Cancer surveillance series: non-Hodgkin's lymphoma incidence by histologic subtype in the United States from 1978 through 1995. J Natl Cancer Inst 2000; 92 (15) 1240-1251
    CrossrefPubMedGoogle Scholar
  • 14 Peh SC, Poppema S. Lymphoma: an introduction into historical background, classification schemes, aetiology, geographical variation and epidemiological trend. Malays J Pathol 2001; 23 (02) 49-63
    PubMedGoogle Scholar
  • 15 Akhter A, Rahman M, Majid N, Shermin S., Saleheen M., Rajib R., Ullah S., Haque N., Akond A.. (2014). Histological Subtypes of Non-Hodgkin's Lymphoma in Different Age and Sex Groups. Bangladesh Medical Journal 41 (01) 32-36
    CrossrefGoogle Scholar
  • 16 Yu XQ, Chen WH, O'Connell DL. Improved survival for non-Hodgkin lymphoma patients in New South Wales, Australia. BMC Cancer 2010; 10: 231
    CrossrefPubMedGoogle Scholar
  • 17 Mitterlechner T, Fiegl M, Mühlböck H, Oberaigner W, Dirnhofer S, Tzankov A. Epidemiology of non-Hodgkin lymphomas in Tyrol/Austria from 1991 to 2000. J Clin Pathol 2006; 59 (01) 48-55
    CrossrefPubMedGoogle Scholar
  • 18 Hazar B, Paydas S, Zorludemir S, Sahin B, Tuncer I. Prognostic significance of microvessel density and vascular endothelial growth factor (VEGF) expression in non-Hodgkin's lymphoma. Leuk Lymphoma 2003; 44 (12) 2089-2093
    CrossrefPubMedGoogle Scholar
  • 19 Aggarwal D, Srivastava G, Gupta R, Pant L, Krishan G, Singh S. Angiogenesis in Non-Hodgkin's Lymphoma: An Intercategory Comparison of Microvessel Density. ISRN Hematol 2012; 2012: 943089
    CrossrefPubMedGoogle Scholar
  • 20 d'Amore F, Brincker H, Grønbaek K. et al; Danish Lymphoma Study Group. Non-Hodgkin's lymphoma of the gastrointestinal tract: a population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. J Clin Oncol 1994; 12 (08) 1673-1684
    CrossrefPubMedGoogle Scholar
  • 21 Koch P, del Valle F, Berdel WE. et al; German Multicenter Study Group. Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 2001; 19 (18) 3861-3873
    Google Scholar
  • 22 Papaxoinis G, Papageorgiou S, Rontogianni D. et al. Primary gastrointestinal non-Hodgkin's lymphoma: a clinicopathologic study of 128 cases in Greece. A Hellenic Cooperative Oncology Group study (HeCOG). Leuk Lymphoma 2006; 47 (10) 2140-2146
    CrossrefPubMedGoogle Scholar
  • 23 Falzon M, Isaacson PG. Histological classification of the non-Hodgkin's lymphoma. Blood Rev 1990; 4 (02) 111-115
    CrossrefPubMedGoogle Scholar
  • 24 Jaffe ES, Harris NL, Stein H, Vardiman JW. (Eds) WHO Classification of Tumours. Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press; 2008
    Google Scholar
  • 25 Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin's lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin's lymphoma classification project. Ann Oncol 1998; 9 (07) 717-720
    CrossrefPubMedGoogle Scholar
  • 26 Haddadin WJ. Malignant lymphoma in Jordan: a retrospective analysis of 347 cases according to the World Health Organization classification. Ann Saudi Med 2005; 25 (05) 398-403
    CrossrefPubMedGoogle Scholar
  • 27 Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin's lymphoma in India: a study of 2773 lymphomas using R.E.A.L. and WHO classifications. Ann Oncol 2000; 11 (Suppl 1): 63-67
    CrossrefPubMedGoogle Scholar
  • 28 Vose J, Armitage J, Weisenburger D. International T-Cell Lymphoma Project. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008; 26 (25) 4124-4130
    CrossrefPubMedGoogle Scholar
  • 29 Piccaluga PP, Agostinelli C, Califano A. et al. Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. J Clin Invest 2007; 117 (03) 823-834
    CrossrefPubMedGoogle Scholar
  • 30 Tumwine LK, Agostinelli C, Campidelli C. et al. Immunohistochemical and other prognostic factors in B cell non Hodgkin lymphoma patients, Kampala, Uganda. BMC Clin Pathol 2009; 9: 11-15
    CrossrefPubMedGoogle Scholar
  • 31 Choi JW, Kim SS, Kim EY, Heran M. Peripheral T-cell lymphoma in the neck: CT findings of lymph node involvement. AJNR Am J Neuroradiol 2006; 27 (05) 1079-1082
    PubMedGoogle Scholar
  • 32 Haque MD. A Study on Frequency, Histologic Types and Immunohistochemistry of T Cell Lymphomas, M. Phil. Thesis. Bangladesh: University of Dhaka; 1991. 12. 34-39
    Google Scholar
  • 33 Vacca A, Ribatti D, Ruco L. et al. Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas. Br J Cancer 1999; 79 (5-6): 965-970
    CrossrefPubMedGoogle Scholar
  • 34 Reilly JT, Nash JR, Mackie MJ, McVerry BA. Distribution of fibronectin and laminin in normal and pathological lymphoid tissue. J Clin Pathol 1985; 38 (08) 849-854
    CrossrefPubMedGoogle Scholar
  • 35 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 (1-2): 45-53
    CrossrefPubMedGoogle Scholar
  • 36 Arias V, Soares FA. Vascular density (tumor angiogenesis) in non-Hodgkin's lymphomas and florid follicular hyperplasia: a morphometric study. Leuk Lymphoma 2000; 40 (1-2): 157-166
    CrossrefPubMedGoogle Scholar
  • 37 Salven P, Teerenhovi L, Joensuu H. A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin's lymphoma. Blood 1997; 90 (08) 3167-3172
    CrossrefPubMedGoogle Scholar
  • 38 Salven P, Orpana A, Teerenhovi L, Joensuu H. Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma: a single-institution study of 200 patients. Blood 2000; 96 (12) 3712-3718
    CrossrefPubMedGoogle Scholar
  • 39 Bertolini F, Paolucci M, Peccatori F. et al. Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma. Br J Haematol 1999; 106 (02) 504-509
    CrossrefPubMedGoogle Scholar
  • 40 Foss HD, Araujo I, Demel G, Klotzbach H, Hummel M, Stein H. Expression of vascular endothelial growth factor in lymphomas and Castleman's disease. J Pathol 1997; 183 (01) 44-50
    CrossrefPubMedGoogle Scholar
  • 41 Ozbudak IH, Akkaya B, Karpuzoğlu G. Vascular endothelial growth factor expression in low and high grade B-cell non-Hodgkin's lymphomas. Turk Patoloji Derg 2011; 27 (03) 204-209
    PubMedGoogle Scholar
  • 42 Ganjoo KN, Moore AM, Orazi A, Sen JA, Johnson CS, An CS. The importance of angiogenesis markers in the outcome of patients with diffuse large B cell lymphoma: a retrospective study of 97 patients. J Cancer Res Clin Oncol 2008; 134 (03) 381-387
    CrossrefPubMedGoogle Scholar
  • 43 Ribatti D, Vacca A, Marzullo A. et al. 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 (02) 171-175
    CrossrefPubMedGoogle Scholar
  • 44 Gratzinger D, Zhao S, Tibshirani RJ. et al. Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy. Lab Invest 2008; 88 (01) 38-47
    CrossrefPubMedGoogle Scholar
  • 45 Streubel B, Chott A, Huber D. et al. Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas. N Engl J Med 2004; 351 (03) 250-259
    CrossrefPubMedGoogle Scholar
  • 46 Gianelli U, Vener C, Raviele PR. et al. VEGF expression correlates with microvessel density in Philadelphia chromosome-negative chronic myeloproliferative disorders. Am J Clin Pathol 2007; 128 (06) 966-973
    CrossrefPubMedGoogle Scholar