RESUMO
Infiltrating ductal breast cancer (IDC) is the principal tumor associated-malignancy in Mexican women. In IDC, the development of intermittent hypoxia leads to an adaptive response coordinated by the transcriptional factor HIF-1α. In the present pilot, retrospective/cross-sectional study, the HIF-1α expression was analyzed in 102 tru-cut biopsies from female patients (51 ± 12 years) without previous clinical treatment and compared to 31 normal breast biopsies. The 102 IDC samples corresponded to 56% of HER2-/HR+; 8% of HER2+/HR-; 22% of triple positive (HER2+/HR+); and 14% of triple negative (TN, HER2-/HR-) subtypes. To assess HIF-1α functionality, proteomic and kinetic analysis of glycolytic as well as mitochondrial enzymes, were determined. Validation of HIF-1α as cancer biomarker was assessed by determining the contents of the commonly used biomarkers c-MYC, Ki67, and H- and K-RAS, as well as metastatic and autophagy proteins. Proteomic analysis revealed that HIF-1α, c-MYC, HER2 and COXIV contents were significantly increased in all IDC subtypes vs. normal tissue. The contents and activities of glycolytic proteins were similar between normal and IDC samples, except for HER2-/HR+ where a substantial increase of HKII was observed. Significant increase in 2OGDH and E-cadherin was detected for TN samples vs. other IDC subtypes and for normal samples. These results clearly indicated that HIF-1α + COXIV + c-MYC (+ HER2 for HER2+ subtype) may be useful to depict a breast cancer metabolic marker pattern for diagnosis, whereas the contents of HIF-1α + c-MYC + 2OGDH + E-cadherin may be an alternative useful and reliable signature for TN subtype cancer prognosis.
Assuntos
Carcinoma Ductal de Mama/genética , Proteômica , Receptor ErbB-2/genética , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patologia , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , México , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/biossíntese , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Breast cancer is the second most frequent tumor in Mexico 30-50% are diagnosed in locally advanced stages requiring neoadjuvant chemotherapy. The overexpression of HER-2/neu has been identified as a chemotherapy response predictor. The objective of our study was to identify response predictive factors to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer. Data were collected from clinical records of patients with neoadjuvant anthracycline-based chemotherapy, for clinical stage III breast cancer from 1992 to 1997. Paraffin blocks were reviewed to determine histologic grade, HER-2/neu expression, and ploidy. Patients were divided in two groups: A, 56 cases responding to chemotherapy and, B, 20 nonresponders. Mean age was 50.1 and 45.4 for groups A and B, respectively (OR 7.02, p = 0.004), and those premenopausal were 43% and 70%, respectively (OR 3.1, p = 0.04). Mean tumor size was 5 cm in responders and 8 cm for nonresponders (OR 4, p = 0.02). Clinical stage III-B 16% and 70% for groups A and B (OR 12.2, p = 0.000); tumors were aneuploid in 39% of responders and 18.7% for nonresponders. HER-2 /neu was overexpressed in 64.2% and 50% for groups A and B (OR 3.6, p = 0.06). On multivariate analysis significance was conserved only for age, clinical stage, and size. HER-2/neu lost significance. Age and size were importantly related to tumor response, a higher percentage of HER-2/neu overexpression was observed in responders, without significance due to small sample size. It would be important to study a larger number of patients to obtain more conclusive results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Retention of barium within appendix following a gastrointestinal tract study may predispose in rare instances to narrowing of appendiceal lumen, thus contributing to development of acute appendicitis. We present the case of a 42-year-old woman in whom this sequence of events was recognized who presented with clinical signs of acute appendicitis 9 days after barium swallow test was performed. Patients must be informed increased chance for development of appendicitis in these cases and be instructed to recognize early symptoms. Surgical treatment is reserved for symptomatic patients and prophylactic appendectomy is not reccommended.
Assuntos
Apendicite/induzido quimicamente , Sulfato de Bário/efeitos adversos , Meios de Contraste/efeitos adversos , Doença Aguda , Adulto , Duodeno/diagnóstico por imagem , Esôfago/diagnóstico por imagem , Feminino , Humanos , Radiografia , Estômago/diagnóstico por imagemRESUMO
Objetivo. Evaluar las diferencias entre pacientes con cáncer de mama sobrevivientes y fallecidas, todas ellas en etapa IV y con metástasis supraclavicular o en axila contralateral al ingreso, con el propósito de identificar los factores que se asociaron a la sobrevida. Métodos. De los expedientes de 13 años (1975-88) se obtuvieron dos grupos de 10 pacientes cada uno: el grupo 1 fue de pacientes vivas sin actividad tumoral y sobrevida mayor a cinco años; el grupo 2 tuvo una sobrevida menor a cinco años y fallecieron por el tumor. En ambos grupos se evaluaron datos clínicos (edad, estado menstrual y tiempo de evolución). Además, se revisaron los factores pronósticos histológicos como tamaño tumoral, estado ganglionar, porcentaje de fibrosis e infiltrado inflamatorio, grado nuclear y necrosis, y se realizaron estudios inmunohistoquímicos de CD34 para angiogénesis, catepsina D, antioncogén p53, oncogén c-erb B2, factor de crecimiento epidérmico, receptores de estrógeno y progesterona y cinética celular; se analizaron curvas de sobrevida en los parámetros que mostraron diferencias intergrupos. Resultados. Los factores asociados a mayor sobrevida fueron: infiltrado inflamatorio escaso (p=0.001), fibrosis escasa (p=0.07), menor expresión de p53 (p=0.03) y tener receptores para estrógenos (p=0.03); hubo otros factores marginales: tener menor de 6 ganglios positivos (p=0.007), y tener receptor de progesterona (p=0.07)