Análise quantitativa de neutrófilos, mastócitos e eosinófilos no adenocarcinoma prostático humano
DOI:
https://doi.org/10.11606/issn.1679-9836.v102i5e-208256Palavras-chave:
Câncer de próstata, Inflamação, Neutrófilos, Mastócitos, EosinófilosResumo
Objetivo: Avaliar a relação entre a hiperplasia prostática benigna (HPB) e o adenocarcinoma prostático (AP) por meio da quantificação de neutrófilos, eosinófilos e mastócitos e correlacionar com o grau histopatológico da neoplasia. Metodologia: Este estudo é observacional transversal. Biópsias catalogadas de pacientes foram seccionadas em cortes de 5µm, coradas e analisadas no microscópio de luz. Nessas secções, as células foram quantificadas e comparadas entre as condições HPB e AP por meio de análises estatísticas. Resultados: Foram analisadas biópsias de 47 pacientes, sendo 28 (59,6%) com HPB e 19 (40,4%) com AP. A mediana da idade do grupo com HPB foi 69 anos (intervalo: 54 – 77 anos) e o com AP foi 66 anos (intervalo: 59 – 92 anos). Na análise estatística, foi observado um maior número de neutrófilos extravasculares (p <0,001) e totais (p <0,05) no AP em relação à HPB, porém não houve diferença estatística entre neutrófilos intravasculares, mastócitos e eosinófilos entre os grupos. Ao correlacionar o Escore de Gleason e o influxo de células inflamatórias, foi observado que maiores escores estão associados a menor influxo de neutrófilos e mastócitos intactos. Além disso, foi observado que o volume e o peso prostático com AP podem estar associados com o infiltrado inflamatório. Conclusão: Nesse estudo, foi possível sugerir que o câncer de próstata possui relação com a resposta imune inata pelo influxo exacerbado de neutrófilos no microambiente tumoral e pela influência dessas células no Escore de Gleason e nos valores de peso e volume prostático. Entretanto, novos estudos são necessários para melhor ilustrar o papel dos neutrófilos na tumorigênese.
Downloads
Referências
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. https://doi.org/10.3322/caac.21660
Brasil. Instituto Nacional de Câncer José Alencar Gomes da Silva. Estimativa 2023: incidência do Câncer no Brasil [recurso eletrônico]. Rio de Janeiro (RJ): INCA; 2022 [citado 2023 Ago 07]. Disponível em: https://www.inca.gov.br/publicacoes/livros/estimativa-2023-incidencia-de-cancer-no-brasil.
Bancroft EK, Raghallaigh HN, Page EC, Eeles RA. Updates in Prostate Cancer Research and Screening in Men at Genetically Higher Risk. Curr Genet Med Rep. 2021;9(4):47-58. https://doi.org/10.1007/s40142-021-00202-5.
Pernar CH, Ebot EM, Wilson KM, Mucci LA. The Epidemiology of Prostate Cancer. Cold Spring Harb Perspect Med. 2018;8(12). https://doi.org/10.1101/cshperspect.a030361.
Aaron L, Franco OE, Hayward SW. Review of Prostate Anatomy and Embryology and the Etiology of Benign Prostatic Hyperplasia. Urol Clin North Am. 2016;43(3):279-88. https://doi.org/10.1016/j.ucl.2016.04.012.
Srougi M, Ribeiro LA, Piovesan AC, Colombo JR, Nesrallah A. Doenças da próstata. Rev Med (São Paulo). 2008;87(3). https://doi.org/10.11606/issn.1679-9836.v87i3p166-177.
Humphrey PA. Histopathology of Prostate Cancer. Cold Spring Harb Perspect Med. 2017;7(10). https://doi.org/10.1101/cshperspect.a030411.
Sehn JK. Prostate Cancer Pathology: Recent Updates and Controversies. Mo Med. 2018;115(2):151-5. Disponível em: https://pubmed.ncbi.nlm.nih.gov/30228708/.
Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am J Surg Pathol. 2016;40(2):244-52. https://doi.org/10.1097/PAS.0000000000000530.
Tuong ZK, Loudon KW, Berry B, Richoz N, Jones J, Tan X, et al. Resolving the immune landscape of human prostate at a single-cell level in health and cancer. Cell Rep. 2021;37(12):110132. https://doi.org/10.1016/j.celrep.2021.110132.
Abbas AK, Lichtman AH, Pillai S. Imunologia celular e molecular. Rio de Janeiro: Elsevier; 2015. 552 p.
De Wever O, Mareel M. Role of tissue stroma in cancer cell invasion. J Pathol. 2003;200(4):429-47. https://doi.org/10.1002/path.1398.
Strasner A, Karin M. Immune Infiltration and Prostate Cancer. Front Oncol. 2015;5:128. https://doi.org/10.3389/fonc.2015.00128.
Nakai Y, Nonomura N. Inflammation and prostate carcinogenesis. Int J Urol. 2013;20(2):150-60. https://doi.org/10.1111/j.1442-2042.2012.03101.x.
Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860-7. https://doi.org/10.1038/nature01322.
Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. Curr Opin Immunol. 2007;19(2):209-16. https://doi.org/10.1016/j.coi.2007.01.001.
Hempel HA, Cuka NS, Kulac I, Barber JR, Cornish TC, Platz EA, et al. Low Intratumoral Mast Cells Are Associated With a Higher Risk of Prostate Cancer Recurrence. Prostate. 2017;77(4):412-24. https://doi.org/10.1002/pros.23280.
Shiao SL, Chu GC, Chung LW. Regulation of prostate cancer progression by the tumor microenvironment. Cancer Lett. 2016;380(1):340-8. https://doi.org/10.1016/j.canlet.2015.12.022.
Zhang E, Dai F, Mao Y, He W, Liu F, Ma W, et al. Differences of the immune cell landscape between normal and tumor tissue in human prostate. Clin Transl Oncol. 2020;22(3):344-50. https://doi.org/10.1007/s12094-019-02128-5.
Zhang Y, Zhou CK, Rencsok EM, Fall K, Lotan TL, Loda M, et al. A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer. Cancer Epidemiol Biomarkers Prev. 2019;28(12):2047-54. https://doi.org/10.1158/1055-9965.EPI-19-0713.
Wu SQ, Su H, Wang YH, Zhao XK. Role of tumor-associated immune cells in prostate cancer: angel or devil? Asian J Androl. 2019;21(5):433-7. https://doi.org/10.4103/aja.aja_47_19.
Galdiero MR, Varricchi G, Loffredo S, Mantovani A, Marone G. Roles of neutrophils in cancer growth and progression. J Leukoc Biol. 2018;103(3):457-64. https://doi.org/10.1002/JLB.3MR0717-292R.
Bekes EM, Schweighofer B, Kupriyanova TA, Zajac E, Ardi VC, Quigley JP, et al. Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation. Am J Pathol. 2011;179(3):1455-70. https://doi.org/10.1016/j.ajpath.2011.05.031.
Melegh Z, Oltean S. Targeting Angiogenesis in Prostate Cancer. Int J Mol Sci. 2019;20(11). https://doi.org/10.3390/ijms20112676.
Xiong S, Dong L, Cheng L. Neutrophils in cancer carcinogenesis and metastasis. J Hematol Oncol. 2021;14(1):173. https://doi.org/10.1186/s13045-021-01187-y.
Kuang AG, Nickel JC, Andriole GL, Castro-Santamaria R, Freedland SJ, Moreira DM. Both acute and chronic inflammation are associated with less perineural invasion in men with prostate cancer on repeat biopsy. BJU Int. 2019;123(1):91-7. https://doi.org/10.1111/bju.14428.
Davidsson S, Fiorentino M, Andren O, Fang F, Mucci LA, Varenhorst E, et al. Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(10):2280-7. https://doi.org/10.1158/1055-9965.EPI-11-0373.
Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja p, Ocana A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124. https://doi.org/10.1093/jnci/dju124.
Kawahara T, Kato M, Tabata K, Kojima I, Yamada H, Kamihira O, et al. A high neutrophil-to-lymphocyte ratio is a poor prognostic factor for castration-resistant prostate cancer patients who undergo abiraterone acetate or enzalutamide treatment. BMC Cancer. 2020;20(1):919. https://doi.org/10.1186/s12885-020-07410-2.
Guan Y, Xiong H, Feng Y, Liao G, Tong T, Pang J. Revealing the prognostic landscape of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: a meta-analysis. Prostate Cancer Prostatic Dis. 2020;23(2):220-31. https://doi.org/10.1038/s41391-020-0209-3.
Rulando M, Siregar GP, Warli SM. Correlation between neutrophil-to-lymphocyte ratio with Gleason score in patients with prostate cancer at Adam Malik Hospital Medan 2013 - 2015. Urol Ann. 2021;13(1):53-5. https://doi.org/10.4103/UA.UA_1_20.
Theoharides TC, Stewart JM. Genitourinary mast cells and survival. Transl Androl Urol. 2015;4(5):579-86. https://doi.org/10.3978/j.issn.2223-4683.2015.10.04.
Galli SJ, Tsai M. Mast cells: versatile regulators of inflammation, tissue remodeling, host defense and homeostasis. J Dermatol Sci. 2008;49(1):7-19. https://doi.org/10.1016/j.jdermsci.2007.09.009.
da Silva EZ, Jamur MC, Oliver C. Mast cell function: a new vision of an old cell. J Histochem Cytochem. 2014;62(10):698-738. https://doi.org/10.1369/0022155414545334
Pittoni p, Colombo MP. The dark side of mast cell-targeted therapy in prostate cancer. Cancer Res. 2012;72(4):831-5. https://doi.org/10.1158/0008-5472.CAN-11-3110.
Komi DEA, Redegeld FA. Role of Mast Cells in Shaping the Tumor Microenvironment. Clin Rev Allergy Immunol. 2020;58(3):313-25. https://doi.org/10.1007/s12016-019-08753-w.
Derakhshani A, Vahidian F, Alihasanzadeh M, Mokhtarzadeh A, Lotfi Nezhad p, Baradaran B. Mast cells: A double-edged sword in cancer. Immunol Lett. 2019;209:28-35. https://doi.org/10.1016/j.imlet.2019.03.011.
Stawerski p, Wagrowska-Danilewicz M, Stasikowska-Kanicka O, Tuka E, Danilewicz M. Augmented mast cell infiltration and microvessel density in prostate cancer. Contemp Oncol (Pozn). 2013;17(4):378-82. https://doi.org/10.5114/wo.2013.37220.
Globa T, Saptefrti L, Ceausu RA, Gaje P, Cimpean AM, Raica M. Mast cell phenotype in benign and malignant tumors of the prostate. Pol J Pathol. 2014;65(2):147-53. https://doi.org/10.5114/pjp.2014.43965.
Wu Z, Chen H, Luo W, Zhang H, Li G, Zeng F, et al. The landscape of immune cells infiltrating in prostate cancer. Front Oncol. 2020;10:517637. https://doi.org/10.3389/fonc.2020.517637.
Hempel Sullivan H, Heaphy CM, Kulac I, Cuka N, Lu J, Barber JR, et al. High extratumoral mast cell counts are associated with a higher risk of adverse prostate cancer outcomes. Cancer Epidemiol Biomarkers Prev. 2020;29(3):668-75. https://doi.org/10.1158/1055-9965.EPI-19-0962.
Wechsler ME, Munitz A, Ackerman SJ, Drake MG, Jackson DJ, Wardlaw AJ, et al. Eosinophils in health and disease: a State-of-the-Art review. Mayo Clin Proc. 2021;96(10):2694-707. https://doi.org/10.1016/j.mayocp.2021.04.025.
Meng J, Liu Y, Guan S, Fan S, Zhou J, Zhang M, et al. The establishment of immune infiltration based novel recurrence predicting nomogram in prostate cancer. Cancer Med. 2019;8(11):5202-13. https://doi.org/10.1002/cam4.2433.
Furbert-Harris p, Parish-Gause D, Laniyan I, Hunter KA, Okomo-Awich J, Vaughn TR, et al. Inhibition of prostate cancer cell growth by activated eosinophils. Prostate. 2003;57(2):165-75. https://doi.org/10.1002/pros.10286.
Furbert-Harris PM, Parish-Gause D, Hunter KA, Vaughn TR, Howland C, Okomo-Awich J, et al. Activated eosinophils upregulate the metastasis suppressor molecule E-cadherin on prostate tumor cells. Cell Mol Biol (Noisy-le-grand). 2003;49(7):1009-16. Disponível em: https://pubmed.ncbi.nlm.nih.gov/14682382/.
Varricchi G, Galdiero MR, Loffredo S, Lucarini V, Marone G, Mattei F, et al. Eosinophils: the unsung heroes in cancer? Oncoimmunology. 2018;7(2):e1393134. https://doi.org/10.1080/2162402X.2017.1393134.
Olsson CA, Lavery HJ, Sebrow D, Akhavan A, Levinson AW, Brajtbord JS, et al. Does size matter? The significance of prostate size on pathologic and functional outcomes in patients undergoing robotic prostatectomy. Arab J Urol. 2011;9(3):159-64. https://doi.org/10.1016/j.aju.2011.10.002.
Freedland SJ, Isaacs WB, Platz EA, Terris MK, Aronson WJ, Amling CL, et al. Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study. J Clin Oncol. 2005;23(30):7546-54. https://doi.org/10.1200/JCO.2005.05.525.
Downloads
Publicado
Edição
Seção
Licença
Copyright (c) 2023 Leonardo Cortez Guerra, Bruna Orbite Garcia, Ana Paula Girol, Thaís Santana Gastardelo Bizotto
Este trabalho está licenciado sob uma licença Creative Commons Attribution-ShareAlike 4.0 International License.
