ORIGINAL ARTICLE
The number of CD163 positive macrophages is associatedwith more advanced skin melanomas, microvessels density and patient prognosis
 
More details
Hide details
1
Department of Pathomorphology, Medical University of Lodz, Poland
 
2
Department of Nephropathology, Medical University of Lodz, Poland
 
3
Health Care Institution Diagnostics Consilio, Lodz, Poland
 
 
Submission date: 2018-12-07
 
 
Final revision date: 2019-01-22
 
 
Acceptance date: 2019-02-20
 
 
Publication date: 2019-12-08
 
 
Pol J Pathol 2019;70(3):217-222
 
KEYWORDS
TOPICS
ABSTRACT
The study was aimed to evaluate the number of TAMs and to investigate whether they have association with microvessels density and patients’ survival times. 46 cases of melanomas, divided into four groups according to the Breslow scale, were tested immunohistochemically with antibodies anti-CD68, CD163, iNOS to vizualized macrophages and anti-CD34 antibody to stain microvessels. The number of macrophages and the microvessels density were counted by hotspot analysis using an image analysis system.
The study revealed increased numbers of CD68 and CD163 positive macrophages in successive stages of Breslow scale, but statistically significant differences were observed only between I and IV group for CD68 positive macrophages, and between I and III, IV group for CD163 positive macrophages. The mean number of the microvessels was significantly increased in group II, III, IV compared to group I. The correlative study showed significant positive correlations between the mean number of CD68 and CD163 positive macrophages and microvessels density. Moreover, the number of CD163 positive macrophages was associated inversely with patient’s survival time.
The results of our study may indicate that higher infiltration of macrophages, especially CD163 positive cells, is associated with more advanced melanomas, microvessels density and worse patient’s prognosis.
REFERENCES (35)
1.
Liu Y, Sheikh MS. Melanoma: Molecular Pathogenesis and Therapeutic Management. Mol Cell Pharmacol 2014; 6: 228.
 
2.
Rastrelli M, Tropea S, Rossi CR, et al. Melanoma: Epidemiology, Risk Factors, Pathogenesis, Diagnosis and Classification. In Vivo 2014; 28: 1005-1012.
 
3.
Giavina-Bianchi MH, Giavina-Bianchi Junior PF, Festa Neto C. Melanoma: Tumor microenvironment and new treatments. An Bras Dermatol 2017; 92: 156-166.
 
4.
Wang H, Yang L, Wang D, et al. Pro-tumor activities of macrophages in the progression of melanoma. Hum Vaccines Immunother 2017; 13: 1556-1562.
 
5.
Falleni M, Savi F, Tosi D, et al. M1 and M2 macrophages’ clinicopathological significance in cutaneous melanoma. Melanoma Res 2017; 27: 200-210.
 
6.
Postovit LM, Seftor EA, Seftor REB, et al. Influence of the microenvironment on melanoma cell fate determination and phenotype. Cancer Res 2006; 66: 7833-7836.
 
7.
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19: 1423-1437.
 
8.
Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25: 677-686.
 
9.
Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature 2008; 454: 436-444.
 
10.
Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23-35.
 
11.
Allavena P, Mantovani A. Immunology in the clinic review series; focus on cancer: Tumour-associated macrophages: Undisputed stars of the inflammatory tumour microenvironment. Clin Exp Immunol 2012; 167: 195-205.
 
12.
Pekarova M, Lojek A. The crucial role of L-arginine in macrophage activation: What you need to know about it. Life Sci 2015; 137: 44-48.
 
13.
Rath M, Müller I, Kropf P, et al. Metabolism via arginase or nitric oxide synthase: Two competing arginine pathways in macrophages. Front Immunol 2014; 5: 1-11.
 
14.
Ma J, Liu L, Che G, et al. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer 2010; 10: 112. 15.
 
15.
Huber R, Meier B, Otsuka A, et al. Tumour hypoxia promotes melanoma growth and metastasis via High Mobility Group Box-1 and M2-like macrophages. Sci Rep 2016; 6: 1-14.
 
16.
Rofstad EK, Danielsen T. Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in human melanoma. Br J Cancer 1998; 77: 897-902.
 
17.
Elder DE, Massi D, Scolyer R, et al. WHO Classification of Skin Tumours. 4th ed. Lyon, IARC 2018; 65-76.
 
18.
Hanahan D, Coussens LM. Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment. Cancer Cell 2012; 21: 309-322.
 
19.
Spaw M, Anant S, Thomas SM. Stromal contributions to the carcinogenic process. Mol Carcinog 2017; 56: 1199-1213.
 
20.
Ribatti D. Mast cells and macrophages exert beneficial and detrimental effects on tumor progression and angiogenesis. Immunol Lett 2013; 152: 83-88.
 
21.
Mantovani A, Sozzani S, Locati M, et al. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23: 549-555.
 
22.
Kim S, Cho SW, Min HS, et al. The Expression of Tumor-Associated Macrophages in Papillary Thyroid Carcinoma. Endocrinol Metab 2013; 28: 192-198.
 
23.
Hillen F, Baeten CI, van de Winkel A, et al. Leukocyte infiltration and tumor cell plasticity are parameters of aggressiveness in primary cutaneous melanoma. Cancer Immunol Immunother 2008; 57: 97-106.
 
24.
Boström MM, Irjala H, Mirtti T, et al. Tumor-associated macrophages provide significant prognostic information in urothelial bladder cancer. PLoS One 2015; 10: 1-16.
 
25.
Johansson CC, Egyházi S, Masucci G, et al. Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanoma. Cancer Immunol Immunother 2009; 58: 1085-1094.
 
26.
Venza M, Visalli M, Beninati C, et al. Cellular mechanisms of oxidative stress and action in melanoma. Oxid Med Cell Longev 2015; 2015: 481782.
 
27.
Spatz A, Batist G, Eggermont AM. The biology behind prognostic factors of cutaneous melanoma. Curr Opin Oncol 2010; 22: 163-168.
 
28.
Jensen TO, Schmidt H, Møller HJ, et al. Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma. J Clin Oncol 2009; 27: 3330-3337.
 
29.
Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004; 4: 71-78.
 
30.
Valkoviæ T, Dobrila F, Melato M, et al. Correlation between vascular endothelial growth factor, angiogenesis, and tumor-associated macrophages in invasive ductal breast carcinoma. Virchows Arch 2002; 440: 583-588.
 
31.
Straume O, Salvesen HB, Akslen LA. Angiogenesis is prognostically important in vertical growth phase melanomas. Int J Oncol 1999; 15: 595-599.
 
32.
Straume O, Akslen LA. Expresson of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. Am J Pathol 2001; 159: 223-235.
 
33.
Jonjic N, Zamolo G, Štifter S, et al. Cytomorphological variations, proliferation and angiogenesis in the prognosis of cutaneous melanoma. Clin Exp Dermatol 2003; 28: 310-314.
 
34.
Pastushenko I, Van den Eynden GG, Vicente-Arregui S, et al. Increased Angiogenesis and Lymphangiogenesis in Metastatic Sentinel Lymph Nodes Is Associated With Nonsentinel Lymph Node Involvement and Distant Metastasis in Patients With Melanoma. Am J Dermatopathol 2016; 38: 338-346.
 
35.
Storr SJ, Safuan S, Mitra A, et al. Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma. Mod Pathol 2012; 25: 493-504.
 
eISSN:2084-9869
ISSN:1233-9687
Journals System - logo
Scroll to top