Microvessel Density and Expression of Vascular Endothelial Growth Factor and Its Receptors in Diffuse Large B-cell Lymphoma Subtypes

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2007 Mar 30

PMID 17392174

Citations 34

Authors

Dita Gratzinger

Shuchun Zhao

Robert J Marinelli

Amy V Kapp

Robert J Tibshirani

Anne S Hammer

Stephen Hamilton-Dutoit

Yasodha Natkunam

Affiliations

Soon will be listed here.

Abstract

Angiogenesis is known to play a major role in neoplasia, including hematolymphoid neoplasia. We assessed the relationships among angiogenesis and expression of vascular endothelial growth factor and its receptors in the context of clinically and biologically relevant subtypes of diffuse large B-cell lymphoma using immunohistochemical evaluation of tissue microarrays. We found that diffuse large B-cell lymphoma specimens showing higher local vascular endothelial growth factor expression showed correspondingly higher microvessel density, implying that lymphoma cells induce local tumor angiogenesis. In addition, local vascular endothelial growth factor expression was higher in those specimens showing higher expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. The germinal center-like and nongerminal center-like subtypes of diffuse large B-cell lymphoma were biologically and prognostically distinct. Interestingly, only in the more clinically aggressive nongerminal center-like subtype were microvessel densities significantly higher in specimens showing higher vascular endothelial growth factor expression; the same was true for the finding of higher vascular endothelial growth factor receptor-1 expression in conjunction with higher vascular endothelial growth factor expression. These differences may have important implications for the responsiveness of the two diffuse large B-cell lymphoma subtypes to anti-vascular endothelial growth factor and anti-angiogenic therapies.

Citing Articles

Vascular Growth in Lymphomas: Angiogenesis and Alternative Ways.

Ribatti D, Tamma R, Annese T, dAmati A, Ingravallo G, Specchia G Cancers (Basel). 2023; 15(12).

PMID: 37370872 PMC: 10296318. DOI: 10.3390/cancers15123262.

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

Singh P, Tahlan A, Mohan H, Singh R J Lab Physicians. 2023; 15(2):282-288.

PMID: 37323605 PMC: 10264129. DOI: 10.1055/s-0042-1760400.

Development of diffuse large B-cell lymphoma after sofosbuvir-ledipasvir treatment for chronic hepatitis C: A case report and literature review.

Sakai H, Miwa T, Ikoma Y, Hanai T, Nakamura N, Imai K Mol Clin Oncol. 2020; 13(3):1.

PMID: 32754315 PMC: 7391802. DOI: 10.3892/mco.2020.2071.

Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: A phase II study.

Ji D, Li Q, Cao J, Guo Y, Lv F, Liu X Oncotarget. 2016; 7(22):33331-9.

PMID: 27129176 PMC: 5078098. DOI: 10.18632/oncotarget.8973.

A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma.

Suhasini A, Wang L, Holder K, Lin A, Bhatnagar H, Kim S Leukemia. 2015; 30(3):617-626.

PMID: 26503641 PMC: 4775385. DOI: 10.1038/leu.2015.302.

References

Kumar S, Gertz M, Dispenzieri A, Lacy M, Wellik L, Fonseca R . Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy. Bone Marrow Transplant. 2004; 34(3):235-9. DOI: 10.1038/sj.bmt.1704555. View

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S . Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998; 4(7):844-7. DOI: 10.1038/nm0798-844. View

Wang E, Teruya-Feldstein J, Wu Y, Zhu Z, Hicklin D, Moore M . Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo. Blood. 2004; 104(9):2893-902. DOI: 10.1182/blood-2004-01-0226. View

Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F . Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol. 1994; 87(3):503-8. DOI: 10.1111/j.1365-2141.1994.tb08304.x. View

Koster A, van Krieken J, MacKenzie M, Schraders M, Borm G, van der Laak J . Increased vascularization predicts favorable outcome in follicular lymphoma. Clin Cancer Res. 2005; 11(1):154-61. View

Shipp M, Ross K, Tamayo P, Weng A, Kutok J, Aguiar R . Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002; 8(1):68-74. DOI: 10.1038/nm0102-68. View

Eisen M, Spellman P, Brown P, Botstein D . Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998; 95(25):14863-8. PMC: 24541. DOI: 10.1073/pnas.95.25.14863. View

Pedersen L, Jurgensen G, Johnsen H . Serum levels of inflammatory cytokines at diagnosis correlate to the bcl-6 and CD10 defined germinal centre (GC) phenotype and bcl-2 expression in patients with diffuse large B-cell lymphoma. Br J Haematol. 2005; 128(6):813-9. DOI: 10.1111/j.1365-2141.2005.05393.x. View

10.

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(8):3167-72. View

11.

Gerber H, Malik A, Solar G, Sherman D, Liang X, Meng G . VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature. 2002; 417(6892):954-8. DOI: 10.1038/nature00821. View

12.

Weidner N, Semple J, Welch W, Folkman J . Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991; 324(1):1-8. DOI: 10.1056/NEJM199101033240101. View

13.

Koster A, Raemaekers J . Angiogenesis in malignant lymphoma. Curr Opin Oncol. 2005; 17(6):611-6. DOI: 10.1097/01.cco.0000181404.83084.b5. View

14.

Cross M, Dixelius J, Matsumoto T, Claesson-Welsh L . VEGF-receptor signal transduction. Trends Biochem Sci. 2003; 28(9):488-94. DOI: 10.1016/S0968-0004(03)00193-2. View

15.

Natkunam Y, Lossos I, Taidi B, Zhao S, Lu X, Ding F . Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation. Blood. 2005; 105(10):3979-86. PMC: 1895083. DOI: 10.1182/blood-2004-08-3112. View

16.

Hans C, Weisenburger D, Greiner T, Gascoyne R, Delabie J, Ott G . Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2003; 103(1):275-82. DOI: 10.1182/blood-2003-05-1545. View

17.

. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993; 329(14):987-94. DOI: 10.1056/NEJM199309303291402. View

18.

Armitage J, Weisenburger D . New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol. 1998; 16(8):2780-95. DOI: 10.1200/JCO.1998.16.8.2780. View

19.

Bellamy W, Richter L, Frutiger Y, Grogan T . Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res. 1999; 59(3):728-33. View

20.

Podar K, Anderson K . The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood. 2004; 105(4):1383-95. DOI: 10.1182/blood-2004-07-2909. View