Abstract
Background: Angiogenesis in non-Hodgkin lymphoma (NHL) has been investigated by a variety of studies. However, the correlation between angiogenesis and the occurrence or prognosis of NHL patients remains controversial. Methods: We performed a systematic and comprehensive retrieval of relevant literatures from PubMed, EMBASE, and Web of Science databases. The quality of the eligible studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: Fifteen eligible studies containing a total of 1373 NHL patients were included in this study. All the eligible studies were high-quality studies scoring ≥6 points. MVD was not different between NHL and control (SMD = 0.281, 95% CI: −1.410 to 1.972, p = 0.745). High MVD was associated with advanced disease stage (OR = 1.580, 95% CI: 1.080–2.311, p = 0.018) and unfavorable OS (HR = 1.656, 95% CI: 1.366–2.009, p = 0.000) but not with PFS (HR = 1.349, 95% CI: 0.852–2.136, p = 0.201). Conclusion: This meta-analysis demonstrated that high MVD was related to advanced disease stage and associated with unfavorable OS of NHL patients.
References
1.
Folkman
J
. Tumor angiogenesis: therapeutic implications
. N Engl J Med
. 1971 Nov 18
;285
(21
):1182
–6
. .2.
Ribatti
D
, Nico
B
, Ranieri
G
, Specchia
G
, Vacca
A
. The role of angiogenesis in human non-Hodgkin lymphomas
. Neoplasia
. 2013 Mar
;15
(3
):231
–8
. .3.
Medinger
M
, Passweg
J
. Role of tumour angiogenesis in haematological malignancies
. Swiss Med Wkly
. 2014 Nov 6
;144
:w14050
. .4.
Folkman
J
. Angiogenesis in cancer, vascular, rheumatoid and other disease
. Nat Med
. 1995 Jan
;1
(1
):27
–31
. .5.
Ruan
J
, Hajjar
K
, Rafii
S
, Leonard
JP
. Angiogenesis and antiangiogenic therapy in non-Hodgkin’s lymphoma
. Ann Oncol
. 2009 Mar
;20
(3
):413
–24
. .6.
Dews
M
, Homayouni
A
, Yu
D
, Murphy
D
, Sevignani
C
, Wentzel
E
, Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster
. Nat Genet
. 2006 Sep
;38
(9
):1060
–5
. .7.
Pegram
MD
, Reese
DM
. Combined biological therapy of breast cancer using monoclonal antibodies directed against HER2/neu protein and vascular endothelial growth factor
. Semin Oncol
. 2002 Jun
;29
(3 Suppl 11
):29
–37
. .8.
Ronca
R
, Benkheil
M
, Mitola
S
, Struyf
S
, Liekens
S
. Tumor angiogenesis revisited: Regulators and clinical implications
. Med Res Rev
. 2017 Nov
;37
(6
):1231
–74
. .9.
Ribatti
D
, Vacca
A
, Dammacco
F
. The role of the vascular phase in solid tumor growth: a historical review
. Neoplasia
. 1999 Oct
;1
(4
):293
–302
. .10.
Koster
A
, Raemaekers
JM
. Angiogenesis in malignant lymphoma
. Curr Opin Oncol
. 2005 Nov
;17
(6
):611
–6
. .11.
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
. .12.
Vacca
A
, Ribatti
D
, Ruco
L
, Giacchetta
F
, Nico
B
, Quondamatteo
F
, 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
. .13.
Koster
A
, van Krieken
JH
, Mackenzie
MA
, Schraders
M
, Borm
GF
, van der Laak
JA
, Increased vascularization predicts favorable outcome in follicular lymphoma
. Clin Cancer Res
. 2005 Jan 1
;11
(1
):154
–61
.14.
Gomez-Gelvez
JC
, Salama
ME
, Perkins
SL
, Leavitt
M
, Inamdar
KV
. Prognostic impact of tumor microenvironment in diffuse large B-cell lymphoma uniformly treated with R-CHOP chemotherapy
. Am J Clin Pathol
. 2016 Apr
;145
(4
):514
–23
. .15.
Taskinen
M
, Jantunen
E
, Kosma
VM
, Bono
P
, Karjalainen-Lindsberg
ML
, Leppä
S
. Prognostic impact of CD31-positive microvessel density in follicular lymphoma patients treated with immunochemotherapy
. Eur J Cancer
. 2010 Sep
;46
(13
):2506
–12
. .16.
Jørgensen
JM
, Sørensen
FB
, Bendix
K
, Nielsen
JL
, Olsen
ML
, Funder
AM
, Angiogenesis in non-Hodgkin’s lymphoma: clinico-pathological correlations and prognostic significance in specific subtypes
. Leuk Lymphoma
. 2007 Mar
;48
(3
):584
–95
. .17.
Cardesa-Salzmann
TM
, Colomo
L
, Gutierrez
G
, Chan
WC
, Weisenburger
D
, Climent
F
, High microvessel density determines a poor outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus chemotherapy
. Haematologica
. 2011 Jul
;96
(7
):996
–1001
. .18.
Gratzinger
D
, Zhao
S
, Tibshirani
RJ
, Hsi
ED
, Hans
CP
, Pohlman
B
, Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy
. Lab Invest
. 2008 Jan
;88
(1
):38
–47
. .19.
Perry
AM
, Cardesa-Salzmann
TM
, Meyer
PN
, Colomo
L
, Smith
LM
, Fu
K
, A new biologic prognostic model based on immunohistochemistry predicts survival in patients with diffuse large B-cell lymphoma
. Blood
. 2012 Sep 13
;120
(11
):2290
–6
. .20.
Tierney
JF
, Stewart
LA
, Ghersi
D
, Burdett
S
, Sydes
MR
. Practical methods for incorporating summary time-to-event data into meta-analysis
. Trials
. 2007 Jun 7
;8
:16
. .21.
Jelicic
J
, Balint
MT
, Jovanovic
MP
, Boricic
N
, Micev
M
, Stojsic
J
, The role of lymphocyte to monocyte ratio, microvessel density and HiGH CD44 tumor cell expression in non Hodgkin lymphomas
. Pathol Oncol Res
. 2016 Jul
;22
(3
):567
–77
. .22.
Arias
V
, Soares
FA
. Vascular density (tumor angiogenesis) in non-Hodgkin’s lymphomas and florid follicular hyperplasia: a morphometric study
. Leuk Lymphoma
. 2000 Dec
;40
(1–2
):157
–66
. .23.
Rizzieri
DA
, Wadleigh
M
, Wikstrand
CJ
, Mann
KP
, Sen
F
, Peterson
BL
, Tenascin and microvessel stromal changes in patients with non-Hodgkin’s lymphoma are isolated to the sites of disease and vary in correlation to disease activity
. Leuk Lymphoma
. 2005 Oct
;46
(10
):1455
–62
. .24.
Ridell
B
, Norrby
K
. Intratumoral microvascular density in malignant lymphomas of B-cell origin
. APMIS
. 2001 Jan
;109
(1
):66
–72
. .25.
Veselá
P
, Tonar
Z
, Sálek
D
, Vokurka
S
, Trněný
M
, Kodet
R
, Microvessel density of mantle cell lymphoma. A retrospective study of its prognostic role and the correlation with the Ki-67 and the mantle cell lymphoma international prognostic index in 177 cases
. Virchows Arch
. 2014 Nov
;465
(5
):587
–97
. .26.
Yang
M
, Zhao
S
, Zhang
X
, Wang
X
, Zhang
M
, Wang
Y
, Effects of microvascular density on primary pulmonary non-Hodgkin’s lymphoma (PPL)
. Tumour Biol
. 2012 Dec
;33
(6
):2143
–50
. .27.
Zhao
S
, Zhang
L
, Zhang
M
, Yao
G
, Zhang
X
, Zhao
W
, Angioimmunoblastic T-cell lymphoma: the effect of initial treatment and microvascular density in 31 patients
. Med Oncol
. 2012 Dec
;29
(4
):2311
–6
. .28.
Huang
J
, Ma
X
, Chen
X
, Liu
X
, Zhang
B
, Minmin
L
, Microvessel density as a prognostic factor in bladder cancer: a systematic review of literature and meta-analysis
. Cancer Biomark
. 2014
;14
(6
):505
–14
. .29.
He
L
, Wang
Q
, Zhao
X
. Microvessel density as a prognostic factor in ovarian cancer: a systematic review and meta-analysis
. Asian Pac J Cancer Prev
. 2015
;16
(3
):869
–74
. .30.
Szade
A
, Grochot-Przeczek
A
, Florczyk
U
, Jozkowicz
A
, Dulak
J
. Cellular and molecular mechanisms of inflammation-induced angiogenesis
. IUBMB Life
. 2015 Mar
;67
(3
):145
–59
. .31.
Whiteford
JR
, De Rossi
G
, Woodfin
A
. Mutually supportive mechanisms of inflammation and vascular remodeling
. Int Rev Cell Mol Biol
. 2016 Jun
;326
:201
–78
. .32.
Hong
WG
, Ko
YS
, Pyo
JS
. Clinicopathological significance and prognostic role of microvessel density in gastric cancer: a meta-analysis
. Pathol Res Pract
. 2017 Dec
;213
(12
):1459
–63
. .33.
Ma
G
, Zhang
J
, Jiang
H
, Zhang
N
, Zhu
Y
, Deng
Y
, Microvessel density as a prognostic factor in esophageal squamous cell cancer patients: a meta-analysis
. Medicine
. 2017 Jul
;96
(29
):e7600
. .34.
Garcia
J
, Hurwitz
HI
, Sandler
AB
, Miles
D
, Coleman
RL
, Deurloo
R
, Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook
. Cancer Treat Rev
. 2020 Jun
;86
:102017
.35.
Stopeck
AT
, Unger
JM
, Rimsza
LM
, LeBlanc
M
, Farnsworth
B
, Iannone
M
, A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515
. Blood
. 2012 Aug 9
;120
(6
):1210
–7
. .36.
Seymour
JF
, Pfreundschuh
M
, Trnĕný
M
, Sehn
LH
, Catalano
J
, Csinady
E
, MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes
. Haematologica
. 2014 Aug
;99
(8
):1343
–9
.37.
Alizadeh
AA
, Eisen
MB
, Davis
RE
, Ma
C
, Lossos
IS
, Rosenwald
A
, Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
. Nature
. 2000 Feb 3
;403
(6769
):503
–11
. .38.
Lenz
G
, Wright
G
, Dave
SS
, Xiao
W
, Powell
J
, Zhao
H
, Stromal gene signatures in large-B-cell lymphomas
. N Engl J Med
. 2008 Nov 27
;359
(22
):2313
–23
. .39.
Gloger
M
, Menzel
L
, Grau
M
, Vion
AC
, Anagnostopoulos
I
, Zapukhlyak
M
, Lymphoma angiogenesis is orchestrated by noncanonical signaling pathways
. Cancer Res
. 2020 Mar 15
;80
(6
):1316
–29
. .40.
Suhasini
AN
, Wang
L
, Holder
KN
, Lin
AP
, Bhatnagar
H
, Kim
SW
, A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma
. Leukemia
. 2016 Mar
;30
(3
):617
–26
. .© 2021 S. Karger AG, Basel
2021
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
