RESUMEN
The evaluation of disseminated epithelial tumor cells in breast cancer patients has generated considerable interest due to its potential association with disease recurrence. Our work was performed to analyze the usefulness of 5 mucin genes expression (MUC2, MUC3, MUC5B, MUC6 and MUC7), using RT-PCR assays, to detect disseminated cancer cells in patients with operable breast cancer. The highest frequencies of positive RT-PCR tests in breast tumor extracts were observed for MUC5B (7/15) and MUC7 (5/12). The best specificity, negative results on all peripheral blood mononuclear (PBMN) cell samples from healthy donors, were shown for MUC2, MUC5B and MUC6 RT-PCR assays. Thus, we selected MUC5B as a target gene for further evaluation. Using a nested RT-PCR, MUC5B mRNA transcripts were detected in 16/31 primary breast tumors (but not in 36 samples of normal PBMN cells) and in the human MCF-7 breast cancer cell line but not in BT20, MDA, T47D and ZR-75 breast cancer cell lines, indicating that MUC5B mRNA is expressed in a population of breast cancer cells. Using this method, 9/46 patients (19.5%) who underwent curative surgery showed positive MUC5B mRNA in bone marrow aspirates obtained prior to surgery, including 5/24 patients (20.8%) with stage I or II breast cancer, without histopathologic lymph node involvement. These results indicate that MUC5B mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cell dissemination. A comparative evaluation between MUC5B mRNA, cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA in all bone marrow aspirates suggests a putative complementation for molecular detection of disseminated carcinoma cells. Considering that breast cancer is characterized by a great phenotypic heterogeneity, the use of multimarker approach could contribute to tumor cell detection in bone marrow and blood.
Asunto(s)
Médula Ósea/metabolismo , Neoplasias de la Mama/metabolismo , Mucinas/biosíntesis , ARN Mensajero/metabolismo , Células de la Médula Ósea , Cartilla de ADN/farmacología , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Mucina 5B , Mucinas/metabolismo , Metástasis de la Neoplasia , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
A partir de una población de 1.311 mujeres con cáncer de mama diagnosticadas, tratadas y seguidas en un mismo centro de patología mamaria, el Centro de Diagnóstico Mamario (CENDIMA), durante un largo lapso de 230 meses, se realiza el análisis descriptivo, el análisis de sobrevida y el de sobrevida libre de enfermedad correlacionándolo con factores pronósticos conocidos para dicha enfermedad. Los dos parámetros de mayor peso pronóstico con valor estadístico para esta población en relación con el intervalo libre de enfermedad fueron el estatus ganglionar y el estadio; el estatus ganglionar y el score histológico final se constituyeron, asimismo, en las variables principales en lo que hace a la sobrevida global. Los datos finales son comparables a los encontrado en la literatura internacional
Asunto(s)
Humanos , Femenino , Neoplasias de la Mama/epidemiología , Análisis de Supervivencia , Bibliografía Nacional , UruguayRESUMEN
A partir de una población de 1.311 mujeres con cáncer de mama diagnosticadas, tratadas y seguidas en un mismo centro de patología mamaria, el Centro de Diagnóstico Mamario (CENDIMA), durante un lapso de 230 meses, se realiza el análisis descriptivo, el análisis de sobrevida y el de sobrevida libre de enfermedad correlacionándolo con factores pronósticos conocidos para dicha enfermedad. Los dos parámetros de mayor peso pronóstico con valor estadístico para esta población en relación con el intervalo libre de enfermedad fueron el estatus ganglionar y el estadio; el estatus ganglionar y el score histológico final se constituyeron, asimismo, en las variables principales en lo que hace a la sobreviva global. Los datos finales obtenidos son comparables a los encontrados en la literatura internacional.
Asunto(s)
Humanos , Adulto , Femenino , Persona de Mediana Edad , Neoplasias de la Mama , Análisis de SupervivenciaRESUMEN
The evaluation of disseminated epithelial tumor cells in breast cancer patients has generated considerable interest due to its potential association with disease recurrence. Our work was performed to analyze the usefulness of 5 mucin genes expression (MUC2, MUC3, MUC5, MUC6 and MUC7), using RT-PCR assays, to detect disseminated cancer cells in patients with operable breast cancer. The highest frequencies of positive RT-PCR tests in breast tumor extracts were observed for MUC5B (7/15) and MUC/ (5/12). The best specificity, negative results on all peripheral blood mononuclear (PBMN) cell samples from health donors, were shown for MUC2, MUC5B and MUC6 RT-PCR assays. Thus, we selected MUC5B as a target gene for further evaluation. Using a nested RT-PCR, MUC5B mRNA transcripts were detected in 16/31 primary breast tumors (but not in 36 samples of normal PBMN cells) and in the human MCF-7 breast cancer cell line but not in BT20, MDA, T47D and ZR-75 breast cancer cell lines, indicating that MUC5B mRNA is expressed in a population of breast cancer cells. Using this method, 9/46 patients (19.5 percent) who underwent curative surgery showed positive MUC5B mRNA in bone marrow aspirated obtained prior to surgery, including 5/24 patients (20.8 percent) with stage I or II breast cancer, without histopathologic lymph node involvement. These results indicate that MUC5B mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cell dissemination. A comparative evaluation between MUC5B mRNA, cytokeratin 19(CK19) mRNA and carcinoembryonic antigen (CEA) mRNA in all bone marrow aspirates suggests a putative complementation for molecular detection of disseminated carcinoma cells. Considering that breast cancer is characterized by a great phenotypic heterogeneity, the use of multimarker approach could contribute to tumor cell detection in bone marrow and blood