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Meme Kanserinde İnflamasyon Tümör Mikroçevresi ve Mast Hücreleri

Year 2025, Volume: 12 Issue: 2, 155 - 160, 28.08.2025
https://doi.org/10.47572/muskutd.1660645

Abstract

Tümör mikroçevresi fibroblastlar, endotel ve bağışıklık hücreleri ve hücre dışı matristen oluşur ve kanseri çevreler. Mast hücreleri, anjiyogenez, stroma immünomodülasyonu ve kanserlerde doku yeniden şekillenmesi ile ilişkilidir. Farklı tümörlerde, tümör mikroçevresine göre antitümör veya güçlendirici etkilere sahip olabilir. Meme kanseri stromasındaki bağışıklık hücreleri, kanser davranışını şekillendiren inflamatuar mikroçevreyi oluşturur. 2017-2020 yılları arasında meme kanseri nedeniyle mastektomi geçiren 85 kadın hastadan alınan örnekler retrospektif olarak değerlendirildi. Hematoksilen-eozin boyalı slaytlar temelinde immünohistokimyasal boyama yapıldı. Mast hücre yoğunluğu, üç yüksek yoğunluklu alanda sayılarak hotspot yöntemi kullanılarak değerlendirildi. Hem tümör çevresi hem de tümör içi yoğunluklar ayrı ayrı kaydedildi ve ortalama sayımlar üç alandan hesaplandı. CD117 üç büyük büyütmede (400x) sayıldı ve tümör içi ve tümör çevresi hücreler ayırt edildi. Tümör içi fibrozis ve lenfositlerin varlığı puanlandı. Sonuçta; tümör çevresi mast hücre sayısı ER negatif olgular ve metastatik lenf nodu sayısı yüksek olgularda ortalamanın altında bulundu. Lobüler karsinom ile tümör içi mast hücre yoğunluğu arasında ters bir ilişki gözlendi. Ek olarak, tümör içi mast hücre yoğunluğu ile artmış tümör boyutu arasında anlamlı bir ters ilişki vardı. Ortalamanın altında tümör içi mast hücre sayısına sahip vakalar, ER negatifliği, yüksek Ki67 proliferasyon indeksi, luminal grup vakaları ve fibrozis yokluğu ile anlamlı bir şekilde ilişkiliydi. Tümörlerde düşük mast hücre sayısı, zayıf prognostik parametrelerle ilişkili bulundu.

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References

  • Raposo TP, Beirao BC, Pang L. et al. Inflammation and cancer: till death tears them apart. Vet J. 2015;205(2):161–74.
  • Galdiero MR, Garlanda C, Jaillon S, et al. Tumor associated macrophages and neutrophils in tumor progression. J Cell Physiol. 2013;228(7):1404–12.
  • Varricchi G, Galdiero MR, Loffredo S, et al. Are mast cells MASTers in cancer? Front Immunol. 2017;8:p. 424.
  • Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18(26):3831–52.
  • Baek JY, Li CY, Pardanani A, et al. Bone marrow angiogenesis in systemic mast cell disease. J Hematother Stem Cell Res. 2002 Feb;11(1):139-46.
  • Dvorak AM, Kissell S. Granule changes of human skin mast cells characteristic of piecemeal degranulation and associated with recovery during wound healing in situ. J Leukoc Biol. 1991;49(2):197–210.
  • Weidner N, Austen KF. Ultrastructural and immunohistochemical characterization of normal mast cells at multiple body sites. J Invest Dermatol. 1991;96: 26S-31S.
  • Theoharides CT, Conti, Mast cells: the JEKYLL and HYDE of tumor growth. Trends Immunol. 2004;25:235–41
  • Kashiwagi S, Yashiro M, Takashima T,et al. c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer. Br J Surg. 2013;100:490–6
  • Dabiri S, Huntsman D, Makretsov N, et al. The presence of stromal mast cells identifies a subset of invasive breast cancers with a favourable prognosis. Mod Pathol. 2004; 17:690–5
  • Ribatti D, Vacca A, Nico B, et al .The role of mast cells in tumour angiogenesis. Br J Haematol. 2001;115:514–21
  • Ch’ng S, Wallis RA, Yuan L, et al. Mast cells and cutaneous malignancies. Modern Pathology. 2005;19(1):149–59
  • Tuna B, Yorukoglu K, Unlu M, et al. Association of mast cells with microvessel density in renal cell carcinomas. Eur Urol. 2006;50(3):530–4.
  • Aponte-López A, Fuentes-Pananá EM, Cortes-Muñoz D, et al. Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer. J Immunol Res. 2018:2584243.
  • Eiro N, Vizoso FJ. Inflammation and cancer. World J Gastrointest Surg. 2012;4(3):62–72.
  • Fernandes JV, Cobucci RN, Jatoba CA, et al. The role of the mediators of inflammation in cancer development. Pathol Oncol Res. 2015;21(3):527–34.
  • Luo Y, Huang W, Zhang H,et al. Prognostic significance of CD117 expression and TP53 missense mutations in triple-negative breast cancer. Oncol Lett. 2018;15(5):6161-70.
  • Garbe JC, Pepin F, Pelissier FA, et al. Accumulation of multipotent progenitors with a basal differentiation bias during aging of human mammary epithelia. Cancer Res. 2012;72(14):3687-701.
  • WHO. World Health Organization. 2012. http://wwwwhoint/cancer/es/
  • Rajput AB, Turbin DA, Cheang MC, et al. Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast Cancer Res Treat. 2008;107(2):249–57.
  • della Rovere F, Granata A, Familiari D, et al. Mast cells in invasive ductal breast cancer: different behavior in high and minimum hormone-receptive cancers. Anticancer Res. 2007;27(4B):2465–71.
  • West RB, Nuyten DS, Subramanian S, et al. Determination of stromal signatures in breast carcinoma. PLoS Biol. 2005;3:e187
  • Ranieri G, Ammendola M, Patruno R, et al. Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients. Int J Oncol. 2009;35(1):115–20.
  • Fakhrjou A, Naghavi-Behzad M, Montazeri V,et al. The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration. South Asian J Cancer. 2016;5(1):5–7.
  • Keser SH, Kandemir NO, Ece D, et al. Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma. Kaohsiung J Med Sci. 2017;33(4):171–80.
  • Löfdahl B, Ahlin C, Holmqvist M, et al. Inflammatory cells in node-negative breast cancer. Acta Oncol. 2012;51(5):680–6.
  • Norashikin AA, Shau KL, Roslina, Huzlinda H, Comparison of Mast Cell Density and Prognostic Factors in InvasiveBreast Carcinoma: A Single-Centre Study in Malaysia. Malays J Med Sci. 2023;30(5):81–90.
  • Glajcar A, Szpor J, Pacek A, et al. The relationship between breast cancer molecular subtypes and mast cell populations in tumor microenvironment. Virchows Arch. 2017;470(5):505-15.
  • Xiang M, Gu Y, Zhao F, et al. Mast cell tryptase promotes breast cancer migration and invasion. Oncol Rep. 2010;23(3):615–9.
  • Samoszuk M, Kanakubo E, Chan JK. Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts. BMC Cancer. 2005;5(1):121.

Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer

Year 2025, Volume: 12 Issue: 2, 155 - 160, 28.08.2025
https://doi.org/10.47572/muskutd.1660645

Abstract

The tumor microenvironment consists of fibroblasts, endothelial and immune cells, and extracellular matrix and envelops the cancer. Mast cells are associated with angiogenesis, immunomodulation of the stroma, and tissue remodeling in cancers. In different tumors, it may have antitumor or potentiating effects in relation to the tumor microenvironment. Immune cells in breast cancer stroma form the inflammatory microenvironment that shapes cancer behavior. Samples taken from 85 female patients who underwent mastectomy due to breast cancer between 2017 and 2020 were evaluated retrospectively. Immunohistochemical staining was performed on the basis of hematoxylin-eosin stained slides. Mast cell density was assessed using the hot-spot method, counting in three high-density areas. Both peritumoral and intratumoral densities were recorded separately, and average counts were calculated from the three fields. CD117 was counted at three high magnifications (400x), and intratumoral and peritumoral cells were distinguished. The presence of intratumoral fibrosis and lymphocytes was scored . Peritumoral mast cell count was found to be below average in ER-negative cases and in cases with high metastatic lymph node count. An inverse relationship was observed between lobular carcinoma and intratumoral mast cell density. In addition, there was a significant inverse relationship between intratumoral mast cell density and increased tumor size. Cases with below average intratumoral mast cell count were significantly associated with ER negativity, high Ki67 proliferation index, , luminal group cases and absence of fibrosis. Low mast cell count in tumors was found to be associated with poor prognostic parameters.

References

  • Raposo TP, Beirao BC, Pang L. et al. Inflammation and cancer: till death tears them apart. Vet J. 2015;205(2):161–74.
  • Galdiero MR, Garlanda C, Jaillon S, et al. Tumor associated macrophages and neutrophils in tumor progression. J Cell Physiol. 2013;228(7):1404–12.
  • Varricchi G, Galdiero MR, Loffredo S, et al. Are mast cells MASTers in cancer? Front Immunol. 2017;8:p. 424.
  • Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18(26):3831–52.
  • Baek JY, Li CY, Pardanani A, et al. Bone marrow angiogenesis in systemic mast cell disease. J Hematother Stem Cell Res. 2002 Feb;11(1):139-46.
  • Dvorak AM, Kissell S. Granule changes of human skin mast cells characteristic of piecemeal degranulation and associated with recovery during wound healing in situ. J Leukoc Biol. 1991;49(2):197–210.
  • Weidner N, Austen KF. Ultrastructural and immunohistochemical characterization of normal mast cells at multiple body sites. J Invest Dermatol. 1991;96: 26S-31S.
  • Theoharides CT, Conti, Mast cells: the JEKYLL and HYDE of tumor growth. Trends Immunol. 2004;25:235–41
  • Kashiwagi S, Yashiro M, Takashima T,et al. c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer. Br J Surg. 2013;100:490–6
  • Dabiri S, Huntsman D, Makretsov N, et al. The presence of stromal mast cells identifies a subset of invasive breast cancers with a favourable prognosis. Mod Pathol. 2004; 17:690–5
  • Ribatti D, Vacca A, Nico B, et al .The role of mast cells in tumour angiogenesis. Br J Haematol. 2001;115:514–21
  • Ch’ng S, Wallis RA, Yuan L, et al. Mast cells and cutaneous malignancies. Modern Pathology. 2005;19(1):149–59
  • Tuna B, Yorukoglu K, Unlu M, et al. Association of mast cells with microvessel density in renal cell carcinomas. Eur Urol. 2006;50(3):530–4.
  • Aponte-López A, Fuentes-Pananá EM, Cortes-Muñoz D, et al. Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer. J Immunol Res. 2018:2584243.
  • Eiro N, Vizoso FJ. Inflammation and cancer. World J Gastrointest Surg. 2012;4(3):62–72.
  • Fernandes JV, Cobucci RN, Jatoba CA, et al. The role of the mediators of inflammation in cancer development. Pathol Oncol Res. 2015;21(3):527–34.
  • Luo Y, Huang W, Zhang H,et al. Prognostic significance of CD117 expression and TP53 missense mutations in triple-negative breast cancer. Oncol Lett. 2018;15(5):6161-70.
  • Garbe JC, Pepin F, Pelissier FA, et al. Accumulation of multipotent progenitors with a basal differentiation bias during aging of human mammary epithelia. Cancer Res. 2012;72(14):3687-701.
  • WHO. World Health Organization. 2012. http://wwwwhoint/cancer/es/
  • Rajput AB, Turbin DA, Cheang MC, et al. Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast Cancer Res Treat. 2008;107(2):249–57.
  • della Rovere F, Granata A, Familiari D, et al. Mast cells in invasive ductal breast cancer: different behavior in high and minimum hormone-receptive cancers. Anticancer Res. 2007;27(4B):2465–71.
  • West RB, Nuyten DS, Subramanian S, et al. Determination of stromal signatures in breast carcinoma. PLoS Biol. 2005;3:e187
  • Ranieri G, Ammendola M, Patruno R, et al. Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients. Int J Oncol. 2009;35(1):115–20.
  • Fakhrjou A, Naghavi-Behzad M, Montazeri V,et al. The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration. South Asian J Cancer. 2016;5(1):5–7.
  • Keser SH, Kandemir NO, Ece D, et al. Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma. Kaohsiung J Med Sci. 2017;33(4):171–80.
  • Löfdahl B, Ahlin C, Holmqvist M, et al. Inflammatory cells in node-negative breast cancer. Acta Oncol. 2012;51(5):680–6.
  • Norashikin AA, Shau KL, Roslina, Huzlinda H, Comparison of Mast Cell Density and Prognostic Factors in InvasiveBreast Carcinoma: A Single-Centre Study in Malaysia. Malays J Med Sci. 2023;30(5):81–90.
  • Glajcar A, Szpor J, Pacek A, et al. The relationship between breast cancer molecular subtypes and mast cell populations in tumor microenvironment. Virchows Arch. 2017;470(5):505-15.
  • Xiang M, Gu Y, Zhao F, et al. Mast cell tryptase promotes breast cancer migration and invasion. Oncol Rep. 2010;23(3):615–9.
  • Samoszuk M, Kanakubo E, Chan JK. Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts. BMC Cancer. 2005;5(1):121.
There are 30 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Original Article
Authors

Leyla Tekin 0000-0003-1172-5536

Melek Ünçel 0000-0002-0304-2682

Publication Date August 28, 2025
Submission Date March 18, 2025
Acceptance Date July 29, 2025
Published in Issue Year 2025 Volume: 12 Issue: 2

Cite

APA Tekin, L., & Ünçel, M. (2025). Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 12(2), 155-160. https://doi.org/10.47572/muskutd.1660645
AMA Tekin L, Ünçel M. Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer. MMJ. August 2025;12(2):155-160. doi:10.47572/muskutd.1660645
Chicago Tekin, Leyla, and Melek Ünçel. “Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 12, no. 2 (August 2025): 155-60. https://doi.org/10.47572/muskutd.1660645.
EndNote Tekin L, Ünçel M (August 1, 2025) Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 12 2 155–160.
IEEE L. Tekin and M. Ünçel, “Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer”, MMJ, vol. 12, no. 2, pp. 155–160, 2025, doi: 10.47572/muskutd.1660645.
ISNAD Tekin, Leyla - Ünçel, Melek. “Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 12/2 (August2025), 155-160. https://doi.org/10.47572/muskutd.1660645.
JAMA Tekin L, Ünçel M. Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer. MMJ. 2025;12:155–160.
MLA Tekin, Leyla and Melek Ünçel. “Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, vol. 12, no. 2, 2025, pp. 155-60, doi:10.47572/muskutd.1660645.
Vancouver Tekin L, Ünçel M. Inflammation Tumor Microenvironment and Mast Cells in Breast Cancer. MMJ. 2025;12(2):155-60.