Abstract
Follicular lymphoma has considerable clinical heterogeneity, and there is a need for easily quantifiable prognostic biomarkers. Microvessel density has been shown to be a useful prognostic factor based on numerical assessment of vessel numbers within histologic sections in some studies, but assessment of tumor neovascularization through angiogenic sprouting may be more relevant. We therefore examined the smallest vessels, single-staining structures measuring less than 30 microm(2) in area, seen within histologic sections, and confirmed that they were neovascular angiogenic sprouts using extended focal imaging. Tissue microarrays composing diagnostic biopsies from patients at the extremes of survival of follicular lymphoma were analyzed with respect to numbers of these sprouts. This analysis revealed higher angiogenic activity in the poor prognostic group and demonstrated an association between increased sprouting and elevated numbers of infiltrating CD163(+) macrophages within the immediate microenvironment surrounding the neovascular sprout.
MeSH Terms
Antigens, CD/metabolism
Antigens, Differentiation, Myelomonocytic/metabolism
Biomarkers, Tumor/metabolism
Biopsy
Humans
Lymphoma, Follicular/pathology
Macrophages/metabolism,pathology
Neovascularization, Pathologic/pathology
Platelet Endothelial Cell Adhesion Molecule-1/metabolism
Prognosis
Receptors, Cell Surface/metabolism
Chemicals
Antigens, CD
Antigens, Differentiation, Myelomonocytic
Biomarkers, Tumor
CD163 antigen
Platelet Endothelial Cell Adhesion Molecule-1
Receptors, Cell Surface
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Clear Andrew J
Centre for Medical Oncology, Queen Mary University of London, Barts, United Kingdom.
Lee Abigail M
Calaminici Maria
Ramsay Alan G
Morris Kelly J
Hallam Simon
Kelly Gavin
Macdougall Finlay
Lister T Andrew
Gribben John G
References (28)
28 references, click to expand
-
High numbers of tumor-associated macrophages have an adverse prognostic value that can be circumvented by rituximab in patients with follicular lymphoma enrolled onto the GELA-GOELAMS FL-2000 trial.
J Clin Oncol. 2008 Jan 20;26(3):440-6
PMID: 18086798
-
Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy.
Eur J Cancer. 2006 Apr;42(6):717-27
PMID: 16520032
-
Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project.
J Clin Oncol. 2009 Sep 20;27(27):4555-62
PMID: 19652063
-
Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma.
J Clin Oncol. 2007 Jun 10;25(17):2426-33
PMID: 17485708
-
Obligatory participation of macrophages in an angiopoietin 2-mediated cell death switch.
Development. 2007 Dec;134(24):4449-58
PMID: 18039971
-
Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.
Cancer Res. 1996 Oct 15;56(20):4625-9
PMID: 8840975
-
Increased vascularization predicts favorable outcome in follicular lymphoma.
Clin Cancer Res. 2005 Jan 1;11(1):154-61
PMID: 15671540
-
Tumor sclerosis but not cell proliferation or malignancy grade is a prognostic marker in advanced-stage follicular lymphoma: the German Low Grade Lymphoma Study Group.
J Clin Oncol. 2007 Aug 1;25(22):3330-6
PMID: 17664481
-
Molecular characterization of lymphatic endothelial cells.
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16069-74
PMID: 12446836
-
Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors.
J Clin Oncol. 2005 Sep 10;23(26):6358-63
PMID: 16155020
-
Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL).
Blood. 2005 Sep 15;106(6):2169-74
PMID: 15933054
-
Histological transformation of non-Hodgkin's lymphoma: a prospective study.
Cancer. 1979 Aug;44(2):645-51
PMID: 383259
-
Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas.
Br J Cancer. 1999 Feb;79(5-6):965-70
PMID: 10070898
-
Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors.
J Immunol. 2010 Jan 15;184(2):702-12
PMID: 20018620
-
Double immunofluorescence labelling of routinely processed paraffin sections.
J Pathol. 2000 Aug;191(4):452-61
PMID: 10918222
-
Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction.
J Invest Dermatol. 2009 Apr;129(4):1016-25
PMID: 18843292
-
Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.
N Engl J Med. 2004 Nov 18;351(21):2159-69
PMID: 15548776
-
Angiogenesis in renal cell carcinoma: the role of tumor-associated macrophages.
Int J Urol. 2009 Oct;16(10):801-7
PMID: 19811548
-
Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center.
J Clin Oncol. 1995 Jan;13(1):140-7
PMID: 7799014
-
Follicular lymphoma international prognostic index.
Blood. 2004 Sep 1;104(5):1258-65
PMID: 15126323
-
Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli.
J Leukoc Biol. 2000 Jan;67(1):97-103
PMID: 10648003
-
Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma.
J Clin Oncol. 2007 Feb 1;25(4):390-8
PMID: 17200149
-
Impact of the tumor microenvironment on prognosis in follicular lymphoma is dependent on specific treatment protocols.
Haematologica. 2009 Jan;94(1):70-7
PMID: 19059937
-
Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma.
Br J Cancer. 2003 Feb 24;88(4):553-9
PMID: 12592369
-
WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature.
Nature. 2005 Sep 15;437(7057):417-21
PMID: 16163358
-
Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands.
Ann Surg Oncol. 2009 Mar;16(3):751-60
PMID: 19116756
-
Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast.
Br J Cancer. 1999 Feb;79(5-6):991-5
PMID: 10070902
-
Number of CD4+ cells and location of forkhead box protein P3-positive cells in diagnostic follicular lymphoma tissue microarrays correlates with outcome.
J Clin Oncol. 2006 Nov 1;24(31):5052-9
PMID: 17033038