RESUMEN

Mammaglobin B (MGB2) and mammaglobin A (MGB1) are proteins expressed in metastatic breast cancers. The early detection of circulating tumor cells (CTCs) in breast cancer patients is crucial to decrease mortality rate. Herein, novel aptamers were successfully selected and characterized against MGB2 and MGB1 proteins using a hybrid SELEX approach. The potential use of the selected aptamers in breast CTC detection was studied using spiked breast cancer cells in whole blood lysate. The results obtained from this study showed that the selected aptamers (MAMB1 and MAMA2) bind to their target breast cancer cell lines with high affinity (low nanomolar Kd values) and specificity. They also bind to their free recombinant target proteins and show minimal non-specific binding to normal and other cancer cell lines. Additionally, they were able to distinguish a low number of breast cancer cells spiked in whole blood lysate containing normal blood cells. The results obtained in this study indicate the great potential for the use of aptamers to detect MGB1 and MGB2 protein biomarkers, expressed on the surface of breast CTCs.

Asunto(s)

Aptámeros de Nucleótidos , Neoplasias de la Mama/sangre , Mamoglobina A/sangre , Mamoglobina B/sangre , Células Neoplásicas Circulantes/metabolismo , Técnica SELEX de Producción de Aptámeros , Biomarcadores de Tumor/sangre , Línea Celular , Biología Computacional , Citometría de Flujo , Pruebas Hematológicas/métodos , Humanos , Microscopía Fluorescente , Técnica SELEX de Producción de Aptámeros/métodos , Sensibilidad y Especificidad

RESUMEN

Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p=0.0019). The maximal expression level was in the samples T1 (p=0.013), stage I BC (p=0.037), GI (p=0.0019). The MGB1 expression positively correlated with expression of estrogen (p = 0,034) and progesterone (p=0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6% and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method.

Asunto(s)

Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Mamoglobina A/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Mamoglobina A/genética , Mamoglobina A/metabolismo , Persona de Mediana Edad , ARN Mensajero/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo

RESUMEN

Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study.

Asunto(s)

Neoplasias de la Mama/sangre , Metástasis Linfática/genética , Mamoglobina A/sangre , Uteroglobina/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Femenino , Humanos , Mamoglobina A/biosíntesis , Pronóstico , ARN Mensajero/biosíntesis , ARN Mensajero/sangre

RESUMEN

Mammaglobin A is a protein that belongs to the secretoglobin superfamily. It has highly specific expression in cells from most breast cancers and may be used to detect circulating or disseminated tumor cells. In addition, mammaglobin A is currently under inves tigation as a potential therapeutic target for immune therapies that target breast cancer. The present review will highlight our current understanding of mammaglobin A at the genetic and protein level and its potential clinical applications. Characteristics of breast cancer and methods used to isolate and detect circulating tumor cells will also be presented.

Asunto(s)

Neoplasias de la Mama/patología , Mamoglobina A/sangre , Células Neoplásicas Circulantes , Biomarcadores de Tumor , Femenino , Humanos , Mamoglobina A/química , Mamoglobina A/genética , Micrometástasis de Neoplasia , Reacción en Cadena en Tiempo Real de la Polimerasa

RESUMEN

AIM: To evaluate the value of peripheral blood mammaglobin (MG) gene expression for diagnosis and prediction of metastasis in breast cancer patients. METHODS: MG expression was detected by nested reverse-transcription polymerase chain reaction in the peripheral blood of 46 females (32 breast cancer, 12 benign breast lesions, 2 no breast abnormalities). In total 28 breast cancer patients were followed up through a period of 34 months for the development of metastasis. RESULTS: MG expression was detected in 16/32 (50%) breast cancer patients but not in patients with benign lesions or healthy participants. Five patients had metastasis at diagnosis. During the 34 months of follow up, five more MG-positive patients showed metastatic lesions and none of the MG negative patients who were followed up developed metastasis. CONCLUSION: The study suggests blood MG expression is a specific molecular marker for detection of occult mammary carcinoma cells of patients with operable breast cancer. It might be of value as a predictor of subsequent metastasis. Large-scale studies and longer follow-up periods are needed.

Asunto(s)

Adenocarcinoma/diagnóstico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Lobular/diagnóstico , Carcinoma Medular/diagnóstico , Carcinoma Papilar/diagnóstico , Mamoglobina A/sangre , Adenocarcinoma/sangre , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/sangre , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/sangre , Carcinoma Lobular/genética , Carcinoma Medular/sangre , Carcinoma Medular/genética , Carcinoma Papilar/sangre , Carcinoma Papilar/genética , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Mamoglobina A/genética , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/sangre , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto Joven

RESUMEN

Different treatment outcomes and prognoses in patients with breast cancer can be observed with similar clinical predictors; this is because the biology of breast cancer is complex and heterogenous, involving multiple unknown contributing factors. We looked for plasma human mammaglobin (hMAM) mRNA by RT-PCR in 82 Korean patients with breast cancer to determine if there is an association between the presence of plasma hMAM mRNA in these patients and known prognostic factors. The prognostic usefulness of detection of plasma hMAM mRNA expression in these patients was also evaluated by determining overall survival and event-free survival. A significant difference was observed in the rate of positivity of plasma hMAM mRNA between the early stages of cancer (stages I-II, 23.4%) and advanced stages (stages III-IV, 82.9%). The expression rates of estrogen receptor, progesterone receptor, and HER-2/neu in the breast tissue of these patients, by immunohistochemistry, were 69.5, 75.6, and 20.7%, respectively. In the univariate analysis, plasma hMAM expression was significantly correlated with high histological and nuclear grades, nodal metastasis, and negative estrogen receptor and progesterone receptor status. Patients negative for plasma hMAM mRNA had significantly higher rates of event-free survival compared to the patients positive for plasma hMAM mRNA. However, no significant association with overall survival was observed for expression of plasma hMAM mRNA (P = 0.16). Qualitative detection of plasma hMAM mRNA appears to be associated with unfavorable prognostic factors and lower rates of event-free survival in patients with breast cancer.

Asunto(s)

Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Mamoglobina A/sangre , Mamoglobina A/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Persona de Mediana Edad , ARN Mensajero/sangre , ARN Mensajero/genética

RESUMEN

OBJECTIVE: A one-tube nested RT-PCR protocol was set up and used to detect mammaglobin A (MGA) expression in blood samples from breast cancer patients. The correlation of MGA detection with prognostic factors was analyzed. DESIGN AND METHODS: Total RNA from nucleated blood cells was extracted from 65 breast cancer patients (before surgery and after the treatments) and 18 healthy subjects and used to detect MGA expression by a modified nested RT-PCR. RESULTS: MGA expression was detected in 38.4% of patients before surgery, and in 50% and 36.8% of post-treatment samples from patients that expressed MGA or were MGA negative before surgery, respectively. MGA detection was associated with the absence of tumor estrogen receptors (p=0.004). CONCLUSIONS: MGA detection by the modified nested RT-PCR is a specific marker for circulating tumor cells in patients with breast carcinoma and a negative prognostic factor for the disease.

Asunto(s)

Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Carcinoma Ductal de Mama/sangre , Carcinoma Lobular/sangre , Mamoglobina A/sangre , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Carcinoma Lobular/terapia , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Metástasis Linfática , Mamoglobina A/genética , Persona de Mediana Edad , Células Neoplásicas Circulantes , Reacción en Cadena de la Polimerasa , Adulto Joven

RESUMEN

The levels of the RNA oncomarkers, telomerase (hTERT), cytokeratin-19 (CK-19) and mammaglobin (MAM) have been investigated in capillary blood of female patients with mammary ductal carcinoma. The study revealed overexpression of all three factors in patients with this pathology. This overexpression was not found in healthy donors and female patients with mammary fibroadenoma. Levels of the RNA oncomarkers return to the normal level within 10 days after successful tumor resection. These results have been used for the development of diagnostic kits, which may be applicable for differential diagnostics, screening and postoperation monitoring of patients with malignant breast tumors

Asunto(s)

Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Carcinoma Ductal de Mama/sangre , Fibroadenoma/sangre , ARN Neoplásico/sangre , Biomarcadores de Tumor/genética , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Diagnóstico Diferencial , Femenino , Fibroadenoma/cirugía , Humanos , Queratina-19/sangre , Queratina-19/genética , Mamoglobina A/sangre , Valor Predictivo de las Pruebas , ARN Neoplásico/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Telomerasa/sangre , Telomerasa/genética