ABSTRACT
Background: In colorectal cancer, BRAF and KRAS mutation are mutually exclusive, but both are independent prognostic factors for the disease. Aim: To determine the frequency of BRAF V600E mutation in colorectal cancer. Material and Methods: A KRAS mutation study was carried out in 100 tissue samples of primary and metastatic adenocarcinomas of colon and rectum from patients aged 61.1 ± 62 years (56 women). Negative KRAS mutation cases underwent study of BRAF V600E mutation by restriction fragment length polymorphism (RFLP) and direct sequencing. Results: Primary tumors were located in the colon and rectum in 88 and six cases respectively. Five were liver metastases and in one case, the sample location was undetermined. Forty two samples were KRAS positive (mutated). In 12 of the 58 KRAS negative (wild type) samples, the V600E mutation in codon 15 of the BRAF gene was demonstrated. No differences in the frequency and distribution of mutations, stratified by gender, age, primary tumor versus metastasis, or tumor location were observed. Conclusions: Twelve percent of KRAS negative colorectal cancer samples showed BRAF gene mutation. Considering that 42% of samples have a KRAS mutation, 54% of patients should not respond to therapies with monoclonal antibodies directed against epidermic growth factor (EGFR) pathway.
Subject(s)
Female , Humans , Male , Middle Aged , Adenocarcinoma/genetics , Colorectal Neoplasms/genetics , Mutation/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Genotype , Neoplasm Staging , Polymorphism, Restriction Fragment LengthABSTRACT
Background: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. Aim: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. Material and Methods: One hundred ninety four samples coming from fve medical centers in Chile, were analyzed. DNA extraction was quantifed determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). Results: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Conclusions: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.
Subject(s)
Humans , DNA, Neoplasm/isolation & purification , Gallbladder Neoplasms/genetics , Chile , Cholecystectomy , DNA, Neoplasm/standards , Gallbladder Neoplasms/pathology , Nucleic Acid Amplification Techniques/methods , Pathology Department, Hospital , Polymerase Chain Reaction/methods , Quality Control , Sample SizeABSTRACT
Background:Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies.Aim: To determine the frequency of HER2 gene overexpression and amplificationin advanced gastric cancer. Material and Methods: One hundred nine advancedgastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62± 12 years respectively, were selected. Three histological patterns (diffuse, intestinaland mixed) were recognized. Automated immunohistochemistry was performedwith monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridization (FISH) for HER2 was performed in positive cases. Results: In 39% of cases,immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15,36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal typeand mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISHwas performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification waspositive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance betweenimmunohistochemical staining and in situ hybridization was 85%. Conclusions: Inadvanced gastric cancer, HER2 gene overexpression or amplification was observed in11% and 12% of cases, respectively.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma/genetics , Gene Amplification/genetics , /genetics , Stomach Neoplasms/genetics , Adenocarcinoma/pathology , Gene Expression , In Situ Hybridization, Fluorescence , Stomach Neoplasms/pathology , Tissue Array AnalysisABSTRACT
Background: KRAS oncogene is involved in colorectal carcinogenesis in 22 to 45% of cases. Aim: To determine the frequency, types and distribution of KRAS mutations in colorectal cancer. Material and Methods: KRAS mutations studies were carried out in primary tumors and metastases of colo-rectal cancer from 56 women aged 60 ± 14 years and 53 men aged 61 ± 11 years. Formalin fixed and paraffin embedded tissue samples were evaluated using RFLP (Restriction Fragment Length Polymorphism) and direct sequencing. Results: Primary tumors were located in the colon and rectum in 82 (75.2%) and 24 cases (20%), respectively. In three cases the extraction site of the tumor sample was unknown. In 46 cases (42.2%) KRAS mutations were demonstrated. The main point mutations were located in codon 12 (80.4%), G12D (39.1%), G12V (24.2%), G12S (6.5%), G12A (4.3%); G12C (4.3%), G12R (2.1%) and 19.6% at codon 13 (G13D). No differences were demonstrated in the frequency and distribution of mutations by gender, age, primary versus metastatic tumors or tumor location. Conclusions: In this series, 42% of colorectal cancer tissue samples had KRAS mutations. Their frequency and distribution are similar to those reported in the literature, except for G12C mutation.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma/genetics , Colonic Neoplasms/genetics , Proto-Oncogene Proteins/genetics , Rectal Neoplasms/genetics , ras Proteins/genetics , Chile , Codon , DNA Mutational Analysis , Mutation , Polymorphism, Restriction Fragment LengthABSTRACT
We report a 34-years-old male, with a history of hepatitis B and human immunodeficiency virus (HIV) infection that was admitted to the hospital with malaise, weight loss, frontal behavior and chest pain. Imaging studies showed two frontal cortical/subcortical nodules. A stereotactic cerebral biopsy showed reactive gliosis and a prominent atypical angiocentric and angiodestructive lymphoid infiltrate containing large pleomorphic CD20 and EBV-positive cells consistent with Lymphomatoid granulomatosis. Other studies were negative. The patient was lost from follow up.
Subject(s)
Adult , Humans , Male , Brain Neoplasms/pathology , Brain/pathology , HIV Seropositivity/complications , Lymphoma, AIDS-Related/pathology , Lymphomatoid Granulomatosis/pathology , Biopsy , Magnetic Resonance Imaging , PrognosisABSTRACT
A pesar de que la mastalgia es una de las causas más frecuentes de consulta de la especialidad, aún no se dispone de un esquema terapéutico razonable. Dada la alta frecuencia de los efectos colaterales significativos con las terapias usuales, teniendo en cuenta que nuevas investigaciones han establecido que la mastopatía fibroquística no tiene un carácter de enfermedad preneoplásica y considerando que no hay una explicación fisiopatológica para la mayoría de las mastalgias, se ha propuesto que el tratamiento de primera línea de esta condición debería ser sintomático, en base a antiinflamatorios no esteroidales. Con el fin de evaluar la utilidad de la Nimesulida en el tratamiento sintomático de las mastalgia funcional se realiza un estudio experimental doble ciego, comparando el efecto de la droga con placebo en 100 pacientes voluntarias, con mastalgia funcional de moderada a grave. En los controles realizados a los 15 días y 30 días por un mismo evaluador se observó que la reducción de la mastalgia, medida en una escala analógica de dolor, fue altamente significativa en el grupo tratado con Nimesulida y no en el grupo tratado con placebo, lo que determinó una diferencia significativa en el comportamiento de ambos grupos. Lo mismo ocurrió con el dolor mamario objetivado durante el examen físico. Se concluye que la Nimesulida resulta ser un tratamiento eficaz de la mastalgia funcional en pacientes con dolor moderado a grave.
Subject(s)
Humans , Female , Anti-Inflammatory Agents, Non-Steroidal , Pain/drug therapy , Breast Diseases/drug therapy , Sulfonamides/therapeutic use , PlacebosABSTRACT
Actinomices es una bacteria oportunista gram positiva no formadora de esporas que aparece ocasionalmente en los genitales femeninos. La infección pélvica es infrecuente, de difícil diagnóstico y se ha demostrado asociación con uso de dispositivos intrauterinos. Material y Método: Se analizaron 36 casos entre 1995 y 2002. Se consideraron edad, tipo y subtipo de método anticonceptivo usado, tiempo de uso del mismo y presencia de síntomas. Resultados: La edad media fue 42 años, con 69 por ciento entre los 36 y los 47. 92 por cineto usuarias de DIU que presentaron un tiempo medio de uso de 11 años, 52 por ciento eran usuarias de Lippes y 48 por ceinto de T de Cobre. Sólo 44 por ciento presentaron algún síntomas. Conclusiones: La detección de Actinomices ocurre casi exclusivamente en usuarias de DIU, más frecuentemente en aquellas entre 35 y 47 años y que presentan un tiempo de uso menor a 15 años. La presencia de síntomas, no parece ser un elemento clínico relevante. No se encontraron diferencias entre usuarias de Lippes y T de Cu en este estudio.