RESUMO
PURPOSE: The objective of this study was to examine the association of EZH2 and paxillin expression and DNA ploidy status with pathological parameters of breast cancer, aiming to correlate tumor phenotype with its malignant behavior. METHODS: EZH2 and paxillin expression and DNA ploidy were evaluated in imprint smear samples obtained from 105 breast tumors after surgical removal. RESULTS: Increased expression of paxillin was associated with p53 expression (p=0.005), Ki-67 expression (p=0.018) and EZH2 expression (p<0.0001). EZH2 expression correlated with estrogen receptor (ER) and progesterone receptor (PR) status (p=0.01 and p=0.035, respectively), and expression of p53 and Ki-67 (p=0.007 and p<0.0001, respectively). Aneuploid tumors were significantly correlated with poor differentiation (p=0.000), stage of disease (p=0.000), size of the primary tumor (p=0.015), presence of nodal metastasis (p=0.001), ER status (p=0.008), cerbB2 status (p=0.012), and expression of Ki-67 (p=0.001) and EGFR (p=0.018). Multivariate analysis of ploidy results using paxillin and EZH2 expression as dependent variables revealed that aneuploid tumors were associated with disease stage and grade of differentiation, cerbB2 expression and EZH2 expression. CONCLUSION: Our results show that aneuploid tumors, EZH2 expression and paxillin expression correlate with more aggressive phenotype of breast cancer.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/química , Carcinoma Lobular/genética , Paxilina/análise , Ploidias , Complexo Repressor Polycomb 2/análise , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Diferenciação Celular , Distribuição de Qui-Quadrado , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Modelos Logísticos , Metástase Linfática , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Fatores de Risco , Carga TumoralRESUMO
INTRODUCTION: The immunocytochemical expression of topoisomerase II alpha (TOP2A), enhancer of zeste homologue 2 (EZH2) and paxillin has recently gained increasing attention. Although previous studies have commented on the clinical usefulness of these markers, their role remains controversial. AIM: The purpose of the study was to investigate the expression of TOP2A, EZH2 and paxillin in relation to classic prognostic parameters and their significance as prognostic markers in imprints of resected breast carcinomas. METHODS: Imprint smears from 55 patients who underwent surgical treatment for primary carcinoma in our department between 2005 and 2006 were studied immunocytochemically with the use of TOP2A, EZH2 and paxillin antibodies. RESULTS: The expression of TOP2A correlated with higher histologic grade, tumor size and negative PR expression. High intensity staining for EZH2 expression was associated with higher histologic grade, negative ER and PR expression and positive Ki-67 expression. The expression of paxillin showed no correlation with estrogen/progesterone and HER2 expression nor with tumor grade and stage. CONCLUSION: Our data indicate that TOP2A and EZH2 expression are related to a more aggressive tumor phenotype. The expression of paxillin failed to correlate with any of the studied clinicopathologic factors. Further studies are needed to verify these results.
Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Paxilina/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose , Complexo Repressor Polycomb 2 , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
BACKGROUND: Aromatase Inhibitor (AI) induced arthralgia is one of the most frequent side effects in breast cancer hormonal therapy, which may become severe in some cases affecting patients' quality of life. The purpose of this study is to investigate alternative treatment of arthralgia, as current treatment options may often prove to be inadequate. MATERIAL-METHODS: According to Morales et al, AI-associated arthralgia syndrome is characterized by tenosynovial changes in MRI, including fluid in tendon sheaths and joints. Initially, furosemide (20 mg per two days) was prescribed by our team, in order to minimize peripheral edema in women receiving aromatase inhibitors. The data collected demonstrated that 16 out of 18 patients had benefited from the addition of a diuretic agent in their adjuvant AI treatment as far as AI induced arthralgia is concerned as well. In this retrospective study, data from 288 women receiving an AI for non-metastatic breast cancer are analyzed in order to define whether chronic diuretic therapy could affect the impact of arthralgia on those patients. RESULTS: 42/288 Patients were receiving chronic diuretic therapy for heart disease or hypertension (Group A), while 246/288 patients had never received any diuretic medication (Group B). At 43.03 months of mean follow up, in Group A arthralgia was developed in 3/42 patients (6.97%) as opposed to 39/246 patients in Group B (15.85%) -p value: 0.01. Other parameters that could affect the impact of arthralgia in both Groups are also analyzed and taken under consideration. CONCLUSION: Despite the low number of patients and the retrospective nature of the study, there was a clear trend to a lower incidence of arthralgia in patients receiving chronic diuretic therapy. We believe that based on this hypothesis generating study further research should be done to assess the value of diuretic agents in the treatment of AI-associated arthralgia.