RESUMEN
Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.
Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico , Endotelina-1/sangre , Precursores de Proteínas/sangre , Adulto , Anciano , Biomarcadores de Tumor/sangre , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal no Infiltrante/sangre , Carcinoma Intraductal no Infiltrante/diagnóstico , Detección Precoz del Cáncer , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Sensibilidad y EspecificidadRESUMEN
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated human tumor suppressor genes, implicated in cell growth and survival and suppressing tumor formation. Loss of PTEN activity, either at the protein or genomic level, has been related to many primary and metastatic malignancies including breast cancer. The present study investigates the heterozygosity, mutation spectrum and protein expression of PTEN in 43 patients with breast cancer or precursor lesions of the breast and 10 healthy individuals. Microsatellite analysis at the PTEN locus using D10S215, D10S541 and D10S579 markers indicated that the observed heterozygosity (Ho) is lower than the expected heterozygosity (Hs) in benign and malignant breast disease. Mutational analysis in exons 1, 5, 7 and 9 of the PTEN gene revealed several mutations, most of which cause truncation of the PTEN protein and consequently loss of activity. Increased circulating levels of PTEN and phosphorylated PTEN protein were also observed by immunostaining in patients with breast cancer and precursor breast lesions. In support, increased PTEN protein expression was detected in corresponding tissue specimens. Our data suggest an association between breast cancer and PTEN mutations, resulting in the production of truncated forms of the corresponding protein, thus indicating that breast carcinogenesis is potentially related to PTEN loss of activity rather than loss of expression. Peripheral blood sampling may provide an advantageous application for the determination of PTEN gene mutations and its protein expression in human cancer.
Asunto(s)
Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Lobular/genética , Pérdida de Heterocigocidad , Mutación/genética , Fosfohidrolasa PTEN/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Estudios de Casos y Controles , Cromosomas Humanos Par 10/genética , ADN de Neoplasias/genética , Femenino , Humanos , Immunoblotting , Técnicas para Inmunoenzimas , Repeticiones de Microsatélite , Fosfohidrolasa PTEN/metabolismo , Fosforilación , Polimorfismo Conformacional Retorcido-Simple , PronósticoRESUMEN
BACKGROUND: Human leukocyte antigen-G (HLA-G) has been closely associated with diagnosis and prognosis in many types of human cancer. The current study aims to investigate soluble (s) HLA-G expression in patients with breast malignancy. PATIENTS AND METHODS: sHLA-G plasma expression was determined in 120 patients with breast cancer and 40 healthy controls using enzyme-linked immunosorbent assay. RESULTS: Plasma sHLA-G levels were significantly higher in breast cancer patients compared to healthy controls (p<0.001), with an area under the receiver operating characteristic (ROC) curve of 0.735 (95% Confidence interval=0.630-0.841, p<0.001). Significantly increased sHLA-G expression was detected in patients with mixed type of coexisting ductal and lobular breast lesions, compared to patients with pure ductal carcinoma or pure lobular neoplasia (p<0.05). CONCLUSION: sHLA-G expression is closely associated with the histological type of breast cancer. Our findings support the application of sHLA-G as a potential biomarker in body fluids for preoperative breast cancer detection and diagnosis.