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. 2018 Apr 12;19(4):1176.
doi: 10.3390/ijms19041176.

Tumor-Associated Macrophages and Mast Cells Positive to Tryptase Are Correlated with Angiogenesis in Surgically-Treated Gastric Cancer Patients

Giuseppe Sammarco  1 , Cosmo Damiano Gadaleta  2 , Valeria Zuccalà  3 , Emre Albayrak  4 , Rosa Patruno  5 , Pietro Milella  6 , Rosario Sacco  7 , Michele Ammendola  8   9 , Girolamo Ranieri  10
Affiliations

Tumor-Associated Macrophages and Mast Cells Positive to Tryptase Are Correlated with Angiogenesis in Surgically-Treated Gastric Cancer Patients

Giuseppe Sammarco et al. Int J Mol Sci. .

Abstract

Mast cells and macrophages can play a role in tumor angiogenesis by stimulating microvascular density (MVD). The density of mast cells positive to tryptase (MCDPT), tumor-associated macrophages (TAMs), and MVD were evaluated in a series of 86 gastric cancer (GC) tissue samples from patients who had undergone potential curative surgery. MCDPT, TAMs, and MVD were assessed in tumor tissue (TT) and in adjacent normal tissue (ANT) by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and, in particular for TT, with important clinico-pathological features. In TT, a significant correlation between MCDPT, TAMs, and MVD was found by Pearson t-test analysis (p ranged from 0.01 to 0.02). No correlation to the clinico-pathological features was found. A significant difference in terms of mean MCDPT, TAMs, and MVD between TT and ANT was found (p ranged from 0.001 to 0.002). Obtained data suggest MCDPT, TAMs, and MVD increased from ANT to TT. Interestingly, MCDPT and TAMs are linked in the tumor microenvironment and they play a role in GC angiogenesis in a synergistic manner. The assessment of the combination of MCDPT and TAMs could represent a surrogate marker of angiogenesis and could be evaluated as a target of novel anti-angiogenic therapies in GC patients.

Keywords: angiogenesis; gastric cancer; macrophages; mast cells; microvascular density; tryptase.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) High MCD in primary gastric cancer tissue section immunostained with the anti-tryptase antibody. Small arrows indicate single red stained mast cells. Big arrows indicate tumoral epithelium. Magnification ×400 (0.19 mm2 area). (B) Low MCD in adjacent normal tissue section immunostained with the anti-tryptase antibody. Small arrows indicate single red stained mast cells. Big arrows indicate normal gastric epithelium. Magnification ×400 (0.19 mm2 area).
Figure 2
Figure 2
(A) High TAMs count in primary gastric cancer tissue section immunostained with the anti-CD68 antibody. Small arrows indicate single red stained macrophages. Big arrow indicates tumoral epithelium. Magnification ×400 (0.19 mm2 area). (B) Low TAMs count in adjacent normal tissue section immunostained with the anti-CD68 antibody. Small arrows indicate single red stained macrophages. Big arrow indicates normal gastric epithelium. Magnification ×400 (0.19 mm2 area).
Figure 3
Figure 3
(A) High MVD in primary gastric cancer tissue section immunostained with the anti-CD31 antibody. Small arrows indicate single red stained microvessels. Small arrows indicate single red stained macrophages. Big arrow indicates tumoral epithelium. Magnification ×400 (0.19 mm2 area). (B) Low MVD in adjacent normal tissue section immunostained with the anti-CD31 antibody. Small arrows indicate single red stained microvessels. Big arrow indicates normal gastric epithelium. Magnification ×400 (0.19 mm2 area).
Figure 4
Figure 4
Actual value regarding MCDPT in TT (red) and ANT (blue).
Figure 5
Figure 5
Actual value regarding TAMs in TT (red) and ANT (blue).
Figure 6
Figure 6
Actual value regarding MVD in TT (red) and ANT (blue).
Figure 7
Figure 7
Correlation between MCDPT and TAMs (r = 0.77, p = 0.02), MCDPT and MVD (r = 0.74, p = 0.02), and TAMS and MVD (r = 0.79, p = 0.01) in gastric cancer tumor tissue.
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