Intratumoral and Peritumoral Mast Cells in Malignant Melanoma: An Immunohistochemical Study

Rajabi, Parvin; Bagheri, Azam; Hani, Mohssen

Intratumoral and Peritumoral Mast Cells in Malignant Melanoma: An Immunohistochemical Study

Document Type : Original Article

Authors

Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: The aim of the current study was to determine mast cell infiltration in malignant melanoma by immunohistochemistry method and its relationship with some of the cancer prognostic factors, including age, sex, and depth of the tumor. Materials and Methods: In this retrospective analytic cross-sectional study, paraffin-embedded tissue blocks of patients with cutaneous malignant melanoma who had undergone excisional biopsy were studied. Mast cells count in studied cases in different stages of the tumor depth was evaluated by mast cell tryptase immunohistochemistry method. Mast cells infiltration was evaluated both inside the tumor and peritumoral area. Tumor infiltrating lymphocytes (TILs) was also determined. Distribution of intratumoral and peritumoral mast cells and TILs was compared in different stages tof tumor depth. Results: In this study, 51 cases with melanoma were studied. Mean ± standard deviation (SD) of intratumoral mast cells in stages 1, 2, and 3 was 9.4 ± 4.2, 10.8 ± 5.1, and 2.1 ± 2.3, respectively (P = 0.000). Mean ± SD of peritumoral mast cells in stages 1, 2 and 3 was 13.4 ± 2.4, 16.6 ± 2.4 and 8.2 ± 4.6, respectively (P = 0.000). There was a significant direct relationship between depth of the tumor and TIL (P = 0.000) and distribution of intratumoral (P = 0.000) and peritumoral mast cells (P = 0.000). Conclusion: Lower distribution of intratumoral and peritumoral mast cells and TILs in higher stages of tumor depth in malignant melanoma suggests a possible inhibitory effect of infiltrating mast cells and lymphocytes on the progression of this tumor.

Keywords

References

1.	Krueger H, Williams D, Chomiak M, Trenaman L. The Economic Burden of Skin Cancer in Canada: Current and Projected. Toronto, ON: Canadian Partnership Against Cancer; 2010. Available from: http://www.krueger.ca/downloads/skincancer.pdf. [Last cited on 2012 Jul 24].
2.	Firoz EF, Warycha M, Zakrzewski J, Pollens D, Wang G, Shapiro R, et al. Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma. Clin Cancer Res 2009;15:2573-80.
3.	Kuphal S, Bosserhoff A. Recent progress in understanding the pathology of malignant melanoma. J Pathol 2009;219:400-9.
4.	Satyamoorthy K, Herlyn M. Cellular and molecular biology of human melanoma. Cancer Biol Ther 2002;1:14-7.
5.	Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochim Biophys Acta 2012;1822:2-8.
6.	Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet 2001;357:539-45.
7.	Dyduch G, Kaczmarczyk K, Okon K. Mast cells and cancer: Enemies or allies? Pol J Pathol 2012;63:1-7.
8.	Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860-7.
9.	Ribatti D, Ennas MG, Vacca A, Ferreli F, Nico B, Orru S, et al. Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur J Clin Invest 2003;33:420-5.
10.	Ribatti D, Vacca A, Ria R, Marzullo A, Nico B, Filotico R, et al. Neovascularisation, expression of fibroblast growth factor-2, and mast cells with tryptase activity increase simultaneously with pathological progression in human malignant melanoma. Eur J Cancer 2003;39:666-74.
11.	Beil WJ, Pammer J. In situ detection of the mast cell proteases chymase and tryptase in human lung tissue using light and electron microscopy. Histochem Cell Biol 2001;116:483-93.
12.	Ch'ng S, Wallis RA, Yuan L, Davis PF, Tan ST. Mast cells and cutaneous malignancies. Mod Pathol 2006;19:149-59.
13.	Homsi J, Kashani-Sabet M, Messina JL, Daud A. Cutaneous melanoma: Prognostic factors. Cancer Control 2005;12:223-9.
14.	Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 1970;172:902-8.
15.	Clark WH Jr, Elder DE, Guerry D 4^th, Braitman LE, Trock BJ, Schultz D, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989;81:1893-904.
16.	Hart PH, Grimbaldeston MA, Finlay-Jones JJ. Sunlight, immunosuppression and skin cancer: Role of histamine and mast cells. Clin Exp Pharmacol Physiol 2001;28:1-8.
17.	Schwartz LB. Analysis of MC (T) and MC (TC) mast cells in tissue. Methods Mol Biol 2006;315:53-62.
18.	Okon K, Stachura J. Increased mast cell density in renal interstitium is correlated with relative interstitial volume, serum creatinine and urea especially in diabetic nephropathy but also in primary glomerulonephritis. Pol J Pathol 2007;58:193-7.
19.	Artuc M, Guhl S, Babina M, Unger T, Steckelings UM, Zuberbier T. Mast cell-derived TNF-a and histamine modify IL-6 and IL-8 expression and release from cutaneous tumor cells. Exp Dermatol 2011;20:1020-2.
20.	Tóth-Jakatics R, Jimi S, Takebayashi S, Kawamoto N. Cutaneous malignant melanoma: Correlation between neovascularization and peritumor accumulation of mast cells overexpressing vascular endothelial growth factor. Hum Pathol 2000;31:955-60.
21.	Schadendorf D, Kohlmus C, Gawlik C, Suter L, Czarnetzki BM. Mast cells in melanocytic tumours. Arch Dermatol Res 1995;287:452-6.
22.	Aris M, Barrio MM, Mordoh J. Lessons from cancer immunoediting in cutaneous melanoma. Clin Dev Immunol 2012;2012:192719.
23.	Oldford SA, Haidl ID, Howatt MA, Leiva CA, Johnston B, Marshall JS. A critical role for mast cells and mast cell-derived IL-6 in TLR2-mediated inhibition of tumor growth. J Immunol 2010;185:7067-76.
24.	Dyduch G, Okon K, Pescarini E. Mast cells in melanocytic skin lesions. An immunohistochemical and quantitative study. Pol J Pathol 2011;62:139-44.
25.	Carlini MJ, Dalurzo MC, Lastiri JM, Smith DE, Vasallo BC, Puricelli LI, et al. Mast cell phenotypes and microvessels in non-small cell lung cancer and its prognostic significance. Hum Pathol 2010;41:697-705.
26.	van Houdt IS, Sluijter BJ, Moesbergen LM, Vos WM, de Gruijl TD, Molenkamp BG, et al. Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression. Int J Cancer 2008;123:609-15.
27.	Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996;77:1303-10.
28.	Tuthill RJ, Unger JM, Liu PY, Flaherty LE, Sondak VK; Southwest Oncology Group. Risk assessment in localized primary cutaneous melanoma: A Southwest Oncology Group study evaluating nine factors and a test of the Clark logistic regression prediction model. Am J Clin Pathol 2002;118:504-11.
29.	Piras F, Colombari R, Minerba L, Murtas D, Floris C, Maxia C, et al. The predictive value of CD8, CD4, CD68, and human leukocyte antigen-D-related cells in the prognosis of cutaneous malignant melanoma with vertical growth phase. Cancer 2005;104:1246-54.
30.	Carlson JA, Slominski A, Linette GP, Mysliborski J, Hill J, Mihm MC Jr, et al. Malignant melanoma 2003: Predisposition, diagnosis, prognosis, and staging. Am J Clin Pathol 2003;120 Suppl: S101-27.

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