_______________________________________________________________________________________________________________________________
OA Maced J Med Sci. 2015 Jun 15; 3(2):209-214. 209
ID Design 2012/DOOEL Skopje
Open Access Macedonian Journal of Medical Sciences. 2015 Jun 15; 3(2):209-214.
http://dx.doi.org/10.3889/oamjms.2015.044
Basic Science
Tumor-Associated Macrophage (TAM) and Angiogenesis in
Human Colon Carcinoma
Manal A. Badawi, Dalia M. Abouelfadl, Sonia L. El-Sharkawy
*
, Wafaa E. Abd El-Aal, Naglaa F. Abbas
Pathology Department, Medical Division, National Research Centre, Dokki, Giza, Egypt
Citation: Badawi MA, Abouelfadl DM, El-Sharkawy SL,
Abd El-Aal WE, Naglaa F. Abbas NF. Tumor-Associated
Macrophage (TAM) and Angiogenesis in Human Colon
Carcinoma. OA Maced J Med Sci. 2015 Jun 15; 3(2):209-
214. http://dx.doi.org/10.3889/oamjms.2015.044
Key words: Adenomatous polyps; cancer colon;
macrophages; angiogenesis; CD68; Factor VIII.
*
Correspondence: Prof. Sonia El-Sharkawy. National
Research Center, Pathology, Dokki, Cairo 2478, Egypt.
Primary E-Mail: elsharkawy60@hotmail.com
Received: 27-Mar-2015; Revised: 15-Apr-2015;
Accepted: 16-Apr-2015; Online first: 27-Apr-2015
Copyright: © 2015 Manal A. Badawi, Dalia M.
Abouelfadl, Sonia L. El-Sharkawy, Wafaa E. Abd El-Aal,
Naglaa F. Abbas. This is an open access article
distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the
original author and source are credited.
Competing Interests: The authors have declared that no
competing interests exist.
Abstract
AIM: This study aimed to clarify how macrophages affect prognosis in cancer colon and their
association with tumor angiogenesis.
MATERIAL AND METHODS: Forty four biopsies of colon carcinoma and 15 of benign
adenomatous polyps were investigated for macrophages infiltration and microvessels density using
immunohistochemistry and image morphometric analysis. Macrophages and blood vessels were
stained immunohistochemically by CD68 and F-VIII markers respectively. The morphometric
analysis was carried out on the immunohistochemically stained slides using the Leica Qwin 500
Image Analyzer. Both of macrophages infiltration and microvessels density were correlated with
histological tumor grade, stage and lymph node metastases and were correlated with each others.
RESULTS: Macrophage infiltration was significantly higher in malignant cases than in benign
polyps. High macrophage infiltration and hypervascularity were significantly correlated with T-
staging and lymph nodes metastasis. A significant correlation was found between macrophage
infiltration and microvessels densitie in malignant tumors where hypervascularity was significantly
correlated with high macrophages infiltration.
CONCLUSION: The significant correlation between macrophage infiltration and tumor
angiogenesis suggests an interaction between macrophages and cancer cells stimulating
microvessels formation, tumor invasion and metastasis in colon cancer. We recommend that
macrophages infiltration should be evaluated to investigate their clinical value in development of
individualized therapeutic regimens for management of colon carcinoma.
Introduction
The tumor microenvironment encompasses a
wide variety of cells including malignant and non-
malignant populations. Non-malignant populations
include stromal cells, an expanding vasculature, and a
leukocyte infiltrate. Macrophages comprise the
dominant portion of the leukocyte population [1].
Tumor-associated macrophages (TAMs),
macrophages existing tumor microenvironment, were
first described in the early 1980s [2, 3]. Till now, TAMs
have been found to play dual functions, both positively
or negatively affect tumor growth through interactions
with the micro-environment, and these actions are
tissue specific [4-6].
Macrophages exist in two distinct polarized
states: one is the classically activated (M1) state and
the other is the alternatively activated (M2) state. M1
macrophages possess antitumor activity, whereas M2
macrophages promote tumor invasion and metastasis
[7, 8]. However, most TAMs have a M2-like
phenotype. CD68 is a pan-macrophage marker
frequently used as a marker for TAMs, and CD68
recognizes both tumoricidal M1 and anti-inflammatory
M2 macrophages [9, 10].
The vast majority of studies with numerous
tumor types, including follicular lymphoma [11], gastric
carcinoma [12], pancreatic cancer [13] and thyroid
carcinoma [14] show that the presence of TAM in the
tumor microenvironment is associated with a worse
prognosis, some studies claim the opposite [15]. The
specific role of TAMs in colon cancer is more