ABSTRACT
BACKGROUND: Genomic DNA methylation, mutations and allelic deletions explain the inactivation of genes involved in cell proliferation and cell cycle control mechanisms. AIM: To analyze the methylation pattern of important genes related to different carcinogenic mechanisms in patients with breast cancer and the relationship with its biological behavior. MATERIAL AND METHODS: Seventy fresh-frozen breast cancer samples were selected. The methylation specific PCR (MSP) test was used to analyze promoter methylation status for genes CDKN2A (p16), hMLH1, APC, CDH1 (Cadherin E) and FHIT. RESULTS: We found methylation in at least one of the genes studied in 88% of cases and in 3 or more genes in 40.5% of cases. The frequencies of promoter hypermethylation of CDKN2A, hMLH1, APC, CDH1 and FHT were 41.4%, 11.4%, 52.9%, 70% and 42.9%, respectively. We found a relationship between CDKN2A methylatlon and better survival (p=0.002). CDH1 methylation and poor histological differentiation (p=0.007), hMLH1 methylation and non-Mapuche ethnicity (p=-0.03), APC methylation and larger tumor size (p<0.05), FHIT methylatton and lack of estrogen rectptor IHC expression (p<0.05). CONCLUSIONS: The high frequency of promoter methylation in patients with breast cancer confirms its role in breast carcinogenesis. The finding of alterations in the methylation pattern of genes studied and its association with prognostic factors is a helpful tool in the search of new criteria for clinical and therapeutic decision making.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Promoter Regions, Genetic , Carcinoma, Ductal, Breast/genetics , Genes, Tumor Suppressor , DNA Methylation , Breast Neoplasms/genetics , Gene Amplification/genetics , Cadherins/genetics , Carcinoma, Ductal, Breast/pathology , Case-Control Studies , Genes, APC , Acid Anhydride Hydrolases/genetics , Breast Neoplasms/pathology , Nuclear Proteins/genetics , Neoplasm Proteins/genetics , Carrier Proteins , Polymerase Chain Reaction/methodsABSTRACT
BACKGROUND: Subserous gallbladder carcinoma is difficult to diagnose and treat. There are no tissue markers with prognostic value in this type of tumor. AIM: To study the immunohistochemical expression of E-cadherin alpha and beta catenin in subserous gallbladder carcinoma. PATIENTS AND METHODS: One hundred seventeen subjects (103 women and 14 men aged 62 and 69 years as a mean, respectively), were studied. Thirty five gallbladder samples without evidence of cancer were used as controls. Expression of markers was studied with standard immunohistochemical techniques for formalin fixed and paraffin embedded tissue. RESULTS: Ninety seven percent of tumors were adenocarcinoma. A lower or absent expression of E-cadherin, alpha catenin and beta catenin was observed in 26, 33 and 29 per cent, respectively. Actuarial five years survival was 37 per cent. No association between macroscopic features of the tumor and survival was observed. Well differentiated tumors had a 73 per cent survival, whereas less differentiated tumors had a 30 per cent survival. Tumors with a normal expression of the markers had a slightly better survival, although not significant (p = 0.06). CONCLUSIONS: Approximately 30 per cent of subserous gallbladder carcinoma have an abnormal expression of E-cadherin, alpha catenin and beta catenin. This abnormal expression has no relationship with prognosis and is probably secondary to the aberrant genic expression of the tumor.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Cytoskeletal Proteins , Cadherins/metabolism , Cystadenocarcinoma, Serous/metabolism , Biomarkers, Tumor/metabolism , Gallbladder Neoplasms/metabolism , Immunohistochemistry , Survival Analysis , Analysis of Variance , Cystadenocarcinoma, Serous/immunology , Gallbladder Neoplasms/immunology , Prognosis , Trans-Activators/metabolismABSTRACT
Con el propósito de conocer características del cáncer vesicular en jóvenes, estudiamos un grupo de pacientes menores de 40 años en relación a pacientes de mayor edad de igual patología. Desde enero de 1980 a diciembre de 1991, se diagnosticaron 286 pacientes portadores de cáncer vesicular, de los cuales 28(8,7 por ciento ) fueron menores de 40 años. Estos pacientes se compararon a un grupo de 42 pacientes mayores de 40 años. Entre los jóvenes el cáncer se detectó en estadios más precoces, lo que permitió efectuar una colecistectomía más frecuente (p<0,05). A pesar de que los jóvenes tenían enfermedad menos avanzada al momento del diagnóstico, durante las reintervenciones efectuadas fue más frecuente observado el compromiso metastásico en el grupo de pacientes jóvenes. Del mismo modo, las curvas de sobrevida de ambos grupos no variaron e incluso cuando los grupos fueron analizados de acuerdo a diferentes niveles de invasión, el grupo de pacientes jóvenes tuvo un peor comportamiento. Como conclusión del trabajo podemos resaltar la importancia de este tipo de tumor en la población menor de 40 años y su probable mayor malignidad en relación a pacientes de mayor edad