Carcinoma mamário ductal invasor: correlação da expressão imunoistoquímica deAXL e ß-catenina com a agressividade tumoral
Barra lateral de artigos
Conteúdo do artigo principal
Resumo
Introdução: O carcinoma ductal invasor corresponde ao tipo histológico mais comum da mama coexistindo com formas diferentes de evolução clínica, graduação histológica, expressão de determinados marcadores teciduais e perfis genômicos que procuram melhor entendimento da doença.
Objetivo: Analisar a correlação dos marcadores ß-catenina e AXL com a agressividade tumoral, tendo como referência a sobrevida global, progressão tumoral e fatores prognósticos histopatológicos.
Método: Foi realizado estudo de 101 amostras de carcinoma mamário ductal invasor. Foram incluídas aquelas com diagnóstico do tipo ductal, submetidas inicialmente à biópsia ou tratamento cirúrgico definitivo. Incluiu-se para fins de controle 20 amostras de carcinoma intraductal, 35 de fibroadenoma mamário e 10 de tecido mamário sem qualquer alteração. Foram excluídos os submetidos à quimioterapia neoadjuvante, que não tivessem amostra tumoral prévia ao tratamento quimioterápico, que perderam o seguimento, e com dados incompletos.
Resultado: Quando analisada a expressão da ß-catenina, foi negativa. Quanto ao AXL foram observados diferentes graus de expressão sem significância estatística entre eles.
Conclusão: Quando analisados adenocarcinoma mamário do tipo ductal invasor em TMA não houve correlação na expressão de ß-catenina e AXL quando comparados a sobrevida global, progressão tumoral e grau histológico.
Detalhes do artigo
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Referências
Wilkes GM. Targeted therapy: attacking cancer with molecular and immunological targeted agents. Asia Pac J Oncol Nurs. 2018;13(2):137-55. https://doi.org/10.4103/apjon.apjon_79_17
Anastasiadi Z, Lianos GD, Ignatiadou E, Harissis HV, Mitsis M. Breast cancer in young women: an overview. Updates Surg. 2017;69:313-7. https://doi.org/10.1007/s13304-017-0424-1
Peregrino AAF, Vianna CM de M, de Almeida CEV, Gonzáles GB, Machado SCF, Costa e Silva FV, et al. Análise de custo-efetividade do rastreamento do câncer de mama com mamografia convencional, digital e ressonância. Cien Saude Colet. 2012;17(1):215-22. https://doi.org/10.1590/S1413-81232012000100023
Majewski JM, Lopes ADF, Davoglio T, Leite JC de C. Quality of life of women recovering from breast cancer after being subjected to mastectomies compared with those who had conservative surgery: a review of the literature. Cien Saude Colet. 2012;17(3):707-16. https://doi.org/10.1590/s1413-81232012000300017
Cosac OM, Soares DA dos S, Daher LMC, Ribeiro-Junior I, Moura LG, Galdino MCA, et al. Surgical treatment of complications resulting from adjuvant radiotherapy: a case report. Rev Bras Cir Plást. 2016;31(4):591-5. https://doi.org/10.5935/2177-1235.2016RBCP0098
Uchôa DM, Cruz DB, Schaefer PG, Pêgas KL, Camcruzzi E. Myofibroblastoma arising in mammary hamartoma: a case report. Patholog Res Int. 2010;1:726829. https://doi.org/10.4061/2010/726829
Matheus VS, Kestelman FP, Canella E de O, Djahjah MCR, Koch HA. Carcinoma medular da mama: correlação anátomo-radiológica. Radiol Bras. 2008;41(6):379-83. https://doi.org/10.1590/S0100-39842008000600007
Oliveira LB, Folgueira MAAK. Biomarcadores no câncer. In: Saito RF, et al. Fundamentos de oncologia molecular. São Paulo: Editora Atheneu; 2015. p. 315-27.
Gopinathk KS, Kumari SJ, Gopinath S, Bhat A, Kundu TK, Swamy S. Chromatin dynamics meet cancer: chromatin protein PC4 in genome organization and breast cancer manifestation. J Clin Oncol. 2014;32(15):e22073. https://doi.org/10.1200/jco.2014.32.15_suppl.e22073
Bahadir EB, Sezgintürk MK. Label-free, ITO-based immunosensor for the detection of a cancer biomarker: receptor for activated C kinase 1. Analyst. 2016;141:5618-26. https://doi.org/10.1039/c6an00694a
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403-10. https://doi.org/10.1111/j.1365-2559.1991.tb00229.x
Elston CW. The assessment of histological differentiation in breast cancer. Aust N Z J Surg. 1984;54:11-5. https://doi.org/10.1111/j.1445-2197.1984.tb06677.x
Zhang R, Chen HJ, Wei B, Zhang HY, Pang ZG, Zhu H, et al. Reproducibility of the Nottingham modification of the Scarff-Bloom-Richardson histological grading system and the complementary value of Ki-67 to this system. Chin Med J (Engl). 2010;123(15):1976-82.
Rakha EA, Reis-Filho JS, Baehner F, Dabbs D, Decker T, Eusebi V, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12(4):207. https://doi.org/10.1186/bcr2607
Vukosavljevic ND, Kanjer K, Markicević M, Todorovic-Rakovic N, Vukotic D, Nesković-Konstantinović Z. Natural course of node-negative breast cancer: high risk-related subgroups. J Exp Clin Cancer Res. 2003;22(4):543-9.
Follana P, Barrière J, Chamorey E, Largillier R, Dadone B, Mari V, et al. Prognostic factors in 401 elderly women with metastatic breast cancer. Oncology. 2014;86(3):143-51. https://doi.org/10.1159/000357781
Sun R, Gao CL, Li DH, Li BJ, Ding YH. Expression status of PIWIL1 as a prognostic marker of colorectal cancer. Dis Markers. 2017;2017:1204937. https://doi.org/10.1155/2017/1204937
Akinyemiju T, Wiener H, Pisu M. Cancer-related risk factors and incidence of major cancers by race, gender, and region: analysis of the NIH-AARP diet and health study. BMC Cancer. 2017;17(1):597. https://doi.org/10.1186/s12885-017-3557-1
Hayes DF, Ethier S, Lippman ME. New guideline for reporting tumor marker studies in breast cancer research and treatment. Breast Cancer Res Treat. 2018;100:237-8. https://doi.org/10.1007/s10549-006-9253-5
Cancello G, Maisonneuve P, Mazza M, Montagna E, Rotmensz N, Viale G, et al. Pathological features and survival outcomes of very young patients with early breast cancer: how much is "very young"? Breast. 2013;22:1046-51. https://doi.org/10.1016/j.breast.2013.08.006
Han W, Kang SY, Korean Breast Cancer Society. Relationship between age at diagnosis and outcome of premenopausal breast cancer: age less than 35 years is a reasonable cut-off for defining young age-onset breast cancer. Breast Cancer Res Treat. 2010;119(1):193-200. https://doi.org/10.1007/s10549-009-0388-z
Sabiani L, Houvenaeghel G, Heinemann M, Reyal F, Classe JM, Cohen M, et al. Breast cancer in young women: pathologic features and molecular phenotype. Breast. 2016;29:109-16. https://doi.org/10.1016/j.breast.2016.07.007
Colleoni M, Rotmensz N, Robertson C, Orlando L, Viale G, Renne G, et al. Very young women (<35 years) with breast cancer: features of disease at presentation. Ann Oncol. 2002;13:273-9. https://doi.org/10.1093/annonc/mdf039
Han W, Kim SW, Park IA, Kang D, Kim SW, Yuon YK, et al. Young age: an independent risk factor for disease-free survival in women with operable breast cancer. BMC Cancer. 2004;4:82. https://doi.org/10.1186/1471-2407-4-82
Gnerlich JL, Deshpande AD, Jeffe DB, Sweet A, White N, Margenthaler JA. Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg. 2009;208:341-7. https://doi.org/10.1016/j.jamcollsurg.2008.12.001
Morrison DH, Rahardja D, King E, Peng Y, Sarode VR. Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer. Br J Cancer. 2012;107(2)382-7. https://doi.org/10.1038/bjc.2012.219
Fredholm H, Magnusson K, Lindstrom LS, Tobin NP, Lindman H, Bergh J, et al. Breast cancer in young women and prognosis: how important are proliferation markers? Eur J Cancer. 2017;84:278-89. https://doi.org/10.1016/j.ejca.2017.07.044
Martinez MT, Oltra SS, Peña-Chilet M, Alonso E, Hernando C, Burgues O, et al. Breast cancer in very young patients in a Spanish cohort: age as an independent bad prognostic indicator. Breast Cancer Basic Clin Res. 2019;13:1178223419828766. https://doi.org/10.1177/1178223419828766
Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua MG, Pruneri G, et al. Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol. 2010;10:1974-81. https://doi.org/10.1093/annonc/mdq072
Pang H, Lu H, Song H, Meng Q, Zhao Y, Liu N, et al. Prognostic values of osteopontin-c, E-cadherin and β-catenin in breast cancer. Cancer Epidemiol. 2013;37(6):985-92. https://doi.org/10.1016/j.canep.2013.08.005
Li S, Li S, Sung Y, Li L. The expression of β-catenin in different subtypes of breast cancer and its clinical significance. Tumour Biol. 2014;7693-8. https://doi.org/10.1007/s13277-014-1975-0
Xu J, Prosperi JR, Choudhury N, Olopade OI, Goss KH. β-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells. PLoS ONE. 2015;10(2):e0117097. https://doi.org/10.1371/journal.pone.0117097
Sun M, Zhao H, Xiao Q, Yu Z, Song Z, Yao W, et al. Combined expression of aldehyde dehydrogenase 1A1 and β-catenin is associated with lymph node metastasis and poor survival in breast cancer patients following cyclophosphamide treatment. Oncol Rep. 2015;34(6):3163-73. https://doi.org/10.3892/or.2015.4273
Cuello-Carrión FD, Shortrede JE, Alvarez-Olmedo D, Cayado-Gutiérrez N, Castro GN, Zoppino FCM, et al. HER2 and β-catenin protein location: importance in the prognosis of breast cancer patients and their correlation when breast cancer cells suffer stressful situations. Clin Exp Metastasis. 2015;32(2):151-68.
Kovacs G, Billfeldt NK, Farkas N, Dergez T, Javorhazy A, Banyai D, et al. Cytoplasmic expression of β-catenin is an independent predictor of progression of conventional renal cell carcinoma: a simple immunostaining score. Histopathology. 2017;70(2):273-80. https://doi.org/10.1111/his.13059
Kim Y, Jin D, Lee BB, Cho EY, Han J, Shim YM, et al. Overexpression of β-catenin and cyclin D1 is associated with poor overall survival in patients with stage IA-IIA squamous cell lung cancer irrespective of adjuvant chemotherapy. J Thorac Oncol. 2016;11(12):2193-201. https://doi.org/10.1016/j.jtho.2016.07.021
Jaffer S, Bleiweiss IJ. Beyond hematoxylin and eosin: the role of immunohistochemistry in surgical pathology. Cancer Invest. 2004;22(3):445-65. https://doi.org/10.1081/cnv-200034896
Leong A, Wright J. The contribution of immunohistochemical staining in tumor diagnosis. Histopathology. 1987;11(12):1295-305. https://doi.org/10.1111/j.1365-2559.1987.tb01874.x
Helander K. Kinetic studies of formaldehyde binding in tissue. Biotech Histochem. 1994;69:177-9. https://doi.org/10.3109/10520299409106282
Mason J, O'Leary TJ. Effects of formaldehyde fixation on protein secondary structure: a calorimetric and infrared spectroscopic investigation. J Histochem Cytochem. 1991;39:225-9. https://doi.org/10.1177/39.2.1987266
Hafizi S, Dahlbäck B. Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev. 2006;17:295-304. https://doi.org/10.1016/j.cytogfr.2006.04.004
Corno C, Gatti L, Lanzi C, Zaffaroni N, Colombo D, Perego P. Role of the receptor tyrosine Axl and its targeting in cancer cells. Curr Med Chem. 2016;23:1496-512. https://doi.org/10.2174/0929867323666160405112954
Graham DK, DeRyckere D, Davies KD, Earp HS. The TAM family: phosphatidylserine-sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 2014;14:769-85. https://doi.org/10.1038/nrc3847
Yu H, Liu R, Ma B, Yen HY, Zhou Y, Krasnoperov V, et al. Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma. Br J Cancer. 2015;113:616-25. https://doi.org/10.1038/bjc.2015.237
Lozneanu L, Pinciroli P, Ciobanu DA, Carcangiu ML, Canevari S, Tomassetti A, et al. Computational and immunohistochemical analyses highlight AXL as a potential prognostic marker for ovarian cancer patients. Anticancer Res. 2016;36:4155-63.
Cassinelli G, Zuco V, Gatti L, Lanzi C, Zaffaroni N, Colombo D, et al. Targeting the Akt kinase to modulate survival, invasiveness and drug resistance of cancer cells. Curr Med Chem. 2013;20(15):1923-45. https://doi.org/10.2174/09298673113209990106
Ahmed L, Nalwoga H, Arnes JB, Wabinga H, Micklem DR, Akslen LA. Increased tumor cell expression of Axl is a marker of aggressive features in breast cancer among African women. APMIS. 2015;123:688-96. https://doi.org/10.1111/apm.12403
Jin G, Wang Z, Wang J, Zhang L, Chen Y, Yuan P, et al. Expression of Axl and its prognostic significance in human breast cancer. Oncol Lett. 2017;13:621-8. https://doi.org/10.3892/ol.2016.5524
Goyette MA, Duhamel S, Aubert L, Pelletier A, Savage P, Thibault MP, et al. The receptor tyrosine kinase Axl is required at multiple steps of the metastatic cascade during HER2-positive breast cancer progression. Cell Rep. 2018;23:1476-90. https://doi.org/10.1016/j.celrep.2018.04.019
D’Alfonso TM, Hannah J, Chen Z, Liu Y, Zhou P, Shin SJ. Axl receptor tyrosine kinase expression in breast cancer. J Clin Pathol. 2014;67:690-6. https://doi.org/10.1136/jclinpath-2013-202161
Berclaz G, Altermatt HJ, Rohrbach V, Kieffer I, Dreher E, Andres AC. Estrogen-dependent expression of the receptor tyrosine kinase Axl in normal and malignant human breast. Ann Oncol. 2001;12:819-24. https://doi.org/10.1023/a:1011126330233