Document Type : Original Research


1 Department of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Neurology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran



Background & Objective: Transitional cell carcinoma (TCC) is the world's seventh most common tumor and forms more than 90% of urinary bladder tumors. Invasive tumors have had a poor prognosis, even with surgical treatment and chemotherapy. Some studies have found that an increase of mast cells in TCC is related to the tumor grade and its aggressiveness. This study investigated the relationship between mast cell density (MCD) and features of TCC (tumor stage, grade, prognosis, and recurrence).
 Materials & Methods: Fifty-one cases with TCC were selected, and MCD was determined by immunohistochemistry (IHC) and Giemsa staining. Mortality rate and tumor recurrence were recorded.
 Results: The MCD mean was higher in high-grade tumors than in low-grade tumors (in IHC method: 9.127 vs 5.296; in Giemsa method: 5.512 vs 2.608).  Also, the MCD mean in dead patients was higher than in survived patients (in IHC method: 11.390 vs 6.211; in Giemsa method: 7.460 vs 3.35). Patients with tumor recurrence had a higher MCD mean than those without recurrence (in IHC method: 9.395 vs 5.475; in Giemsa method: 5.715 vs 2.931).
Conclusion:  Using mast cell tryptase and Giemsa, MCD has a positive correlation with tumor grade in TCC. Correlations between MCD, recurrence, prognosis, and tumor stage are probably caused by the effect of tumor grade (all with p <0.05).


  • Transitional Cell Carcinoma (TCC) is the world's seventh most common tumor, and invasive tumors have a bad prognosis, even with aggressive treatment.
  • Analysis of new effective factors on the grade, stage, and prognosis of the tumor has critical value in the treatment of the tumor; and one of this factors is mast cell.
  • This study investigates the relationship between mast cell density and features of transitional cell carcinoma.
  • The MCD mean was higher in high-grade tumors, in dead patients, and in the patients with tumor recurrence.
  • The MCD -using mast cell tryptase and Giemsa - has a positive correlation with tumor grade in TCC.


Main Subjects

Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. European urology. 2017;71(1):96-108. [DOI:10.1016/j.eururo.2016.06.010]

Rafiemanesh H, Lotfi Z, Bakhtazad S, Ghoncheh M, Salehiniya H. The epidemiological and histological trend of bladder cancer in Iran. Journal of cancer research and therapeutics. 2018;14(3):532-6. [DOI:10.4103/0973-1482.172134]

Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, et al. Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. The Journal of urology. 2017;198(3):552-9. [DOI:10.1016/j.juro.2017.04.086]

Abern MR, Dude AM, Tsivian M, Coogan CL. The characteristics of bladder cancer after radiotherapy for prostate cancer. Urologic oncology. 2013;31(8):1628-34. [DOI:10.1016/j.urolonc.2012.04.006]

Cho DS, Hong SY, Kim YK, Kim SI, Kim SJ. Prognostic factors in transitional cell carcinoma of the upper urinary tract after radical nephroureterectomy. Korean journal of urology. 2011;52(5):310-6. [DOI:10.4111/kju.2011.52.5.310]

Lee JY, Joo HJ, Cho DS, Kim SI, Ahn HS, Kim SJ. Prognostic Significance of Substaging according to the Depth of Lamina Propria Invasion in Primary T1 Transitional Cell Carcinoma of the Bladder. Korean journal of urology. 2012;53(5):317-23. [DOI:10.4111/kju.2012.53.5.317]

Rezaianzadeh A, Mohammadbeigi A, Mobaleghi J, Mohammadsalehi N. Survival analysis of patients with bladder cancer, life table approach. Journal of mid-life health. 2012;3(2):88-92. [DOI:10.4103/0976-7800.104468]

Hallgren J, Gurish MF. Mast cell progenitor trafficking and maturation. Advances in experimental medicine and biology. 2011;716:14-28. [DOI:10.1007/978-1-4419-9533-9_2]

Bourn J, Pandey S, Uddin J, Marnett L, Cekanova M. Detection of tyrosine kinase inhibitors-induced COX-2 expression in bladder cancer by fluorocoxib A. Oncotarget. 2019;10(50):5168-80. [DOI:10.18632/oncotarget.27125]

Kim JH, Kang YJ, Kim DS, Lee CH, Jeon YS, Lee NK, et al. The relationship between mast cell density and tumour grade in transitional cell carcinoma of the bladder. The Journal of international medical research. 2011;39(5):1675-81. [DOI:10.1177/147323001103900509]

Sari A, Calli A, Cakalagaoglu F, Altinboga AA, Bal K. Association of mast cells with microvessel density in urothelial carcinomas of the urinary bladder. Annals of diagnostic pathology. 2012;16(1):1-6. [DOI:10.1016/j.anndiagpath.2011.07.001]

Shirodkar SP, Lokeshwar VB. Bladder tumor markers: from hematuria to molecular diagnostics--where do we stand? Expert review of anticancer therapy. 2008;8(7):1111-23. [DOI:10.1586/14737140.8.7.1111]

Keser SH, Kandemir NO, Ece D, Gecmen GG, Gul AE, Barisik NO, et al. Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma. Kaohsiung J Med Sci. 2017;33(4):171-80. [DOI:10.1016/j.kjms.2017.01.005]

Serel TA, Soyupek S, Candir O. Association between mast cells and bladder carcinoma. Urologia internationalis. 2004;72(4):299-302. [DOI:10.1159/000077681]

Ribatti D, Tamma R, Vacca A. Mast Cells and Angiogenesis in Human Plasma Cell Malignancies. International journal of molecular sciences. 2019;20(3). [DOI:10.3390/ijms20030481]

Ribatti D, Crivellato E. Immune cells and angiogenesis. Journal of cellular and molecular medicine. 2009;13(9A):2822-33. [DOI:10.1111/j.1582-4934.2009.00810.x]

Stockmann C, Schadendorf D, Klose R, Helfrich I. The impact of the immune system on tumor: angiogenesis and vascular remodeling. Front Oncol. 2014;4(69):69. [DOI:10.3389/fonc.2014.00069]

Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochimica et biophysica acta. 2012;1822(1):2-8. [DOI:10.1016/j.bbadis.2010.11.010]

Galinsky DS, Nechushtan H. Mast cells and cancer--no longer just basic science. Critical reviews in oncology/hematology. 2008;68(2):115-30. [DOI:10.1016/j.critrevonc.2008.06.001]

Maltby S, Khazaie K, McNagny KM. Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochimica et biophysica acta. 2009;1796(1):19-26. [DOI:10.1016/j.bbcan.2009.02.001]

Xu W, Qian J, Zeng F, Li S, Guo W, Chen L, et al. Protein kinase Ds promote tumor angiogenesis through mast cell recruitment and expression of angiogenic factors in prostate cancer microenvironment. J Exp Clin Cancer Res. 2019;38(1):114. [DOI:10.1186/s13046-019-1118-y]

Ribatti D, Crivellato E. Mast cells, angiogenesis and cancer. Advances in experimental medicine and biology. 2011;716:270-88. [DOI:10.1007/978-1-4419-9533-9_14]

Amini RM, Aaltonen K, Nevanlinna H, Carvalho R, Salonen L, Heikkila P, et al. Mast cells and eosinophils in invasive breast carcinoma. BMC Cancer. 2007;7(1):165. [DOI:10.1186/1471-2407-7-165]

Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunological reviews. 2018;282(1):121-50. [DOI:10.1111/imr.12634]

Ribatti D, Finato N, Crivellato E, Marzullo A, Mangieri D, Nico B, et al. Neovascularization and mast cells with tryptase activity increase simultaneously with pathologic progression in human endometrial cancer. American journal of obstetrics and gynecology. 2005;193(6):1961-5. [DOI:10.1016/j.ajog.2005.04.055]

Marech I, Ammendola M, Gadaleta C, Zizzo N, Oakley C, Gadaleta CD, et al. Possible biological and translational significance of mast cells density in colorectal cancer. World journal of gastroenterology. 2014;20(27):8910-20.

Molderings GJ, Zienkiewicz T, Homann J, Menzen M, Afrin LB. Risk of solid cancer in patients with mast cell activation syndrome: Results from Germany and USA. F1000Research. 2017;6:1889. [DOI:10.12688/f1000research.12730.1]

Eder J, Rogojanu R, Jerney W, Erhart F, Dohnal A, Kitzwogerer M, et al. Mast Cells Are Abundant in Primary Cutaneous T-Cell Lymphomas: Results from a Computer-Aided Quantitative Immunohistological Study. PLoS One. 2016;11(11):e0163661. [DOI:10.1371/journal.pone.0163661]

Marech I, Ammendola M, Sacco R, Capriuolo GS, Patruno R, Rubini R, et al. Serum tryptase, mast cells positive to tryptase and microvascular density evaluation in early breast cancer patients: possible translational significance. BMC Cancer. 2014;14(1):534. [DOI:10.1186/1471-2407-14-534]

Spencer KR, Wang J, Silk AW, Ganesan S, Kaufman HL, Mehnert JM. Biomarkers for Immunotherapy: Current Developments and Challenges. Am Soc Clin Oncol Educ Book. 2016;35(36):e493-503. [DOI:10.14694/EDBK_160766]

Rajput AB, Turbin DA, Cheang MC, Voduc DK, Leung S, Gelmon KA, et al. Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast cancer research and treatment. 2008;107(2):249-57. [DOI:10.1007/s10549-007-9546-3]

Segovia-Mendoza M, Morales-Montor J. Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology. Front Immunol. 2019;10(348):348. [DOI:10.3389/fimmu.2019.00348]