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1.
Tumour Biol ; 35(11): 11621-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25139094

RESUMO

Dystroglycan (DG), a multifunctional protein dimer of non-covalently linked α and ß subunits, is best known as an adhesion and transduction molecule linking the cytoskeleton and intracellular signaling pathways to extracellular matrix proteins. Loss of DG binding, possibly by degradation or disturbed glycosylation, has been reported in a variety of cancers. DG is abundant at astroglial endfeet forming the blood-brain barrier (BBB) and glia limitans; so, we examined if loss of expression is associated with glioma. Expression levels of α-DG and ß-DG were assessed by immunohistochemistry in a series of 78 glioma specimens to determine the relationship with tumor grade and possible prognostic significance. α-DG immunostaining was undetectable in 44 of 49 high-grade specimens (89.8%) compared to 15 of 29 low-grade specimens (51.72%) (P<0.05). Moreover, loss of α-DG expression was an independent predictor of shorter disease-free survival (DFS) (hazards ratio (HR) = 0.142, 95% confidence interval (CI) 0.033-0.611, P=0.0088). Reduced expression of both α-DG and ß-DG was also a powerful negative prognostic factor for DFS (HR=2.556, 95% CI 1.403-4.654, P=0.0022) and overall survival (OS) (HR=2.193, 95% CI 1.031-4.666, P=0.0414). Lack of α-DG immunoreactivity is more frequent in high-grade glioma and is an independent predictor of poor clinical outcome. Similarly, lack of both α-DG and ß-DG immunoreactivity is a strong independent predictor of clinical outcome.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Distroglicanas/metabolismo , Glioma/metabolismo , Recidiva Local de Neoplasia/metabolismo , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
2.
Breast Cancer (Auckl) ; 6: 1-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22259247

RESUMO

BACKGROUND: Recent studies have shown that androgen displays an inhibitory effect on breast cancer cell lines that express androgen receptor (AR) but not estrogen receptor (ER) and progesterone receptor (PR). We have previously reported that approximately 1/3 of ER negative high grade invasive ductal carcinomas express AR. Thus, AR can serve as a potential therapeutic target for this group of patients. AIM: Here we investigated AR expression patterns in 980 consecutive breast carcinomas. RESULTS: We found that (1) AR was expressed more frequently (77%) than ER (61%) and PR (60%) in breast carcinomas; (2) AR expression was associated with ER and PR expression (P < 0.0001), small tumor size (P = 0.0324) and lower Ki-67 expression (P = 0.0013); (3) AR expression was found in 65% of ER negative tumors; (4) AR expression was associated with PR and Ki-67 in ER negative tumors, but not in ER positive tumors; (5) AR expression was higher in ER positive subtypes (Luminal A, Luminal B and Luminal HER2 subtypes, 80%-86%) and lower in ER negative subtypes [HER2, triple negative (TN), and TN EFGR positive subtypes; 52%-66%], with over 50% of TN tumors expressing AR. CONCLUSION: More breast carcinomas express AR than ER and PR, including significant numbers of ER negative and TN tumors, for which AR could serve as a potential therapeutic target.

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