RESUMEN
Epidermal growth factor receptor gene (EGFR) alteration is a common feature in most of glioblastoma multiforme (GBM). Robust response of anti-EGFR treatments has been mostly associated with the EGFR deletion mutant variant III (EGFRvIII) and expression of PTEN. We have performed a prospective trial in order to confirm the efficacy of erlotinib treatment in patients with relapsed GBM who expressed EGFRvIII and PTEN. All patients included in the trial were required to be PTEN (+++), EGFR (+++) and EGFRvIII (+++) positives by immunohistochemistry. This new phase II trial enrolled 40 patients and was design to be stopped in case of fewer than two responses in the first 13 patients. Patient eligibility included histopathology criteria, radiological progression, more than 18 years old, Karnofsky performed status, KPS > 50, and adequate bone marrow and organ function. There was no limit to the number of prior treatments for relapses. No enzyme-inducing antiepileptic drugs were allowed. The primary endpoints were response and progression-free survival at 6 months (PFS6). Thirteen patients (6 men, 7 women) with recurrent GBM received erlotinib 150 mg/day. Median age was 53 years, median KPS was 80, and median prior treatments for relapses were 2. There was one partial response and three stable diseases (one at 18 months). PFS at 6 months was 20 %. Dose reduction for toxicity was not needed in any patient. Dermatitis was the main treatment-related toxicity, grade 1 in 8 patients and grade 2 in 5 patients. No grade 3 toxicity was observed. Median survival was 7 months (95 % IC 1.41-4.7). As conclusion, monotherapy with erlotinib in GBM relapses patients with high protein expression for PTEN (+++), EGFR (+++), and EGFRvlII (+++) showed low toxicity but minimal efficacy and the trial stopped.
Asunto(s)
Neoplasias Encefálicas/terapia , Hemangiopericitoma/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/etiología , Radiocirugia/métodosRESUMEN
BACKGROUND: The presence of the 5569A polymorphism may lead to misdiagnosis of patients susceptible of hereditary hemochromatosis (HH). For that reason, samples containing the Cys282Tyr mutation were revised and the frequency of this polymorphism in our environment was assessed. PATIENTS AND METHOD: Twenty samples were retested and 56 controls were included. The study was performed by PCR-RFLP. RESULTS: The diagnosis was confirmed in 8 cases susceptible of error. However, an amplification deficiency of normal alleles was detected in 2 heterozygous (17%). The allelic frequency of the 5569A polymorphism in the control population was 14.3%. CONCLUSIONS: Although misdiagnosis was not committed, we recommend changing to any primer that does not include the 5569G/A polymorphism in the study of HH.
Asunto(s)
Hemocromatosis/diagnóstico , Intrones/genética , Polimorfismo Genético/genética , ARN de Transferencia de Cisteína/genética , Adulto , Análisis Mutacional de ADN , Femenino , Expresión Génica , Frecuencia de los Genes/genética , Pruebas Genéticas , Antígenos HLA/genética , Hemocromatosis/epidemiología , Humanos , Masculino , Mutación Puntual/genética , España/epidemiologíaRESUMEN
BACKGROUND: To assess the putative prognostic value of K-ras mutations in nonmucinous ovarian tumors, the authors looked for K-ras point mutations at codons 12 and 13 in 144 nonmucinous ovarian tumors. METHODS: A series of 144 consecutive, unselected, archival, nonmucinous ovarian tumors (35 benign, 12 borderline, and 97 malignant) were studied. K-ras mutations at codons 12 and 13 were determined by polymerase chain reaction using the restriction fragment length polymorphism method with mismatched nested primers. Extensive clinicopathologic and follow-up data on all patients were evaluated. RESULTS: The overall prevalence of K-ras mutations at codons 12 and 13 was 30.5% (44/144). In benign tumors, it was 20% (7/35); in borderline tumors, 25% (3/12); and in carcinomas, 35% (34/97). The presence of K-ras point mutations did not correlate with survival. Among the benign tumors, K-ras mutations were detected in three Brenner tumors with a mucinous component. CONCLUSIONS: These results indicate that K-ras mutations are not initial events in the pathogenesis of nonmucinous ovarian tumors and do not appear to be related to survival.
Asunto(s)
Carcinoma/genética , Genes ras/genética , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/genética , Mutación Puntual , Adulto , Anciano , Anciano de 80 o más Años , Codón , ADN de Neoplasias/análisis , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prevalencia , Pronóstico , Análisis de SupervivenciaRESUMEN
K-ras and p53 gene alterations are frequently found in human pancreatic carcinomas and cell lines. The aim of this study was to analyze for the presence of K-ras and p53 gene mutations in hamster pancreatic tumors and cell lines. Mutations at the first coding exon of the K-ras gene and in exons V to VIII of the hamster p53 gene were analyzed in six cell lines (H2T, PC1, PC1.2, PC1.0, WD, and PD) and in N-nitroso-bis(2-oxopropyl)amine-induced pancreatic (n = 9) and extra-pancreatic (n = 4) tumors. K-ras mutations were present in seven of the nine pancreatic tumors and in all extra-pancreatic tumors. No p53 mutations were detected in the tumors. All cell lines analyzed contained K-ras mutations. Moreover, four of the six cell lines contained single amino acid substitutions in the p53 gene. Cell lines derived from nitrosamine-induced pancreatic tumors in the hamster contained K-ras and p53 alterations similar to those found in cell lines derived from human pancreatic carcinomas.
Asunto(s)
Carcinoma Ductal de Mama/genética , Genes p53/genética , Genes ras/genética , Mutación/genética , Neoplasias Pancreáticas/genética , Animales , Carcinógenos , Carcinoma Ductal de Mama/inducido químicamente , Cricetinae , Nitrosaminas , Neoplasias Pancreáticas/inducido químicamente , Polimorfismo Conformacional Retorcido-Simple , Células Tumorales CultivadasRESUMEN
BACKGROUND & AIMS: Mutations at codon 12 of the K-ras gene are present in 65%-100% of carcinomas of human exocrine pancreas and could be used as a potential tumor marker at the tissue level. The purpose of this study was to assess, in large series of patients, the utility of K-ras mutation analysis to evaluate fine-needle aspirates of pancreatic masses. METHODS: One hundred fifteen fine-needle aspirates obtained from 93 patients were evaluated retrospectively. Cytological analysis was based on the review of cell blocks. Mutations were detected by using artificial restriction fragment length polymorphisms using the Hphl and BstNl approaches. RESULTS: The sensitivity and specificity of cell block cytology was 64% and 100%, respectively, for the diagnosis of pancreatic carcinoma. K-ras mutations were detected in 41 pancreatic carcinomas (sensitivity, 59%) and in one mucinous cystic tumor; specificity of ras analysis alone was 100%. The sensitivity of cytology combined with K-ras mutations were 77.6% and 100%, respectively. CONCLUSIONS: The detection of K-ras mutations would have suggested the diagnosis of pancreatic cancer in 14 cases otherwise not detected by cytology alone. K-ras mutation analysis should be restricted to cell blocks containing suspicious, normal-appearing duct cells, or insufficient material in the cytological examination.