Prognostic gene expression signature for high-grade serous ovarian cancer.

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Phenotypic characterization of hereditary epithelial ovarian cancer based on a tissue microarray study.

The pathologic and immunohistochemical features of familial epithelial ovarian cancers are not well understood. We have carried out a comprehensive immunohistochemical study of familial ovarian carcinomas from women with and without BRCA1 or BRCA2 mutations, in order to identify specific and/or common features among these different familial case groups (BRCA1, BRCA2 and non-BRCA1/2) and to identify markers of diagnostic value that might help to select more specific treatments. 73 familial primary ovarian carcinomas were analyzed for the expression of 40 antibodies involved in different genetic pathways using a tissue microarray. Serous carcinomas comprised the majority of all three familial case groups. On the other hand, BRCA1 and BRCA2 carcinomas have similar histopathologic features; i.e. they are often high-grade and are usually diagnosed at a more advanced FIGO stage than non-BRCA1/2 carcinomas. In our series, BRCA1 carcinomas had better clinical evolution and they also more frequently over-expressed PR and P53 than BRCA2 and non-BRCA1/2 carcinomas. Unsupervised cluster analysis and survival analysis identified ERCC1 as a potential marker of better clinical outcome for hereditary epithelial ovarian cancer.

[Tuberculosis in the autopsy. Clinical and pathological study: an analysis of 92 cases of active tuberculosis found in 2,180 autopsies]. / Tuberculosis en la autopsia. Estudio anatomoclínico: análisis de 92 casos encontrados entre 2.180 autopsias.

BACKGROUND AND OBJECTIVE: Tuberculosis is an infectious disease currently having great importance in the daily clinical practice in Spain. Some cases of active tuberculosis are not identified until after the patient had died and an autopsy has been performed. This study has analyzed the clinical and pathological characteristics of patients diagnosed with active tuberculosis in the autopsy. MATERIAL AND METHOD: We reviewed all the autopsies performed in the University Hospital 12 de Octubre of Madrid between 1974 and 2002. The autopsy reports and clinical records were examined in those cases in which active tuberculosis was found. RESULTS: We found 92 cases of active tuberculosis, 57% corresponding to men. Mean age of this group was 64 years. A total of 20% of the patients died within 48 hours after admission. Predisposing factors were identified in 90% of the cases. Dyspnea (24% of cases) and wasting syndrome (23%) were the main symptoms that motivated patients to request medical attention. Up to 30% of cases had normal chest X-ray. Tuberculosis was suspected in only 46% of patients before death. Principal cause of death was tuberculosis in 61% of patients, 52% of patients had pulmonary tuberculosis, 28% suffered from miliary tuberculosis and 20% from extra-pulmonary tuberculosis. The lungs were the most frequently affected organ. Epithelioid granulomas were found in all patients. CONCLUSIONS: Tuberculosis is an uncommon finding in the autopsy as the cause of death. The presence of unspecific symptomatology, insufficient cost-effectiveness of the diagnostic tests and precocious death, are identified as the most frequent causes of undiagnosed tuberculosis.

Tuberculosis en la autopsia. Estudio anatomoclínico: análisis de 92 casos encontrados entre 2.180 autopsias / Tuberculosis in the autopsy. Clinical and pathological study: an analysis of 92 cases of active tuberculosis found in 2.180 autopsies

Fundamento y objetivo. En España, la tuberculosis es una enfermedad con importante relevancia en la práctica clínica diaria. En ocasiones su diagnóstico sorprende como hallazgo en la necropsia. El objetivo de este trabajo ha sido analizar las características clínico-anatomopatológicas que presentan los pacientes diagnosticados de tuberculosis activa en la necropsia. Material y método. Se revisaron retrospectivamente todas las autopsias de adultos realizadas en el Hospital Universitario 12 de Octubre de Madrid entre los años 1974 y 2002. En aquellos pacientes en los que se llegó al diagnóstico de tuberculosis activa se revisó la historia clínica y el informe anatomopatológico según protocolo establecido previamente. Resultados. Se encontraron 92 casos de tuberculosis activa. El 57% correspondía a hombres. La edad media de los pacientes era de 64 años. El 90% de los casos presentaba alguno de los factores predisponentes controlados. El 20% falleció en las primeras 48 horas tras el ingreso. Los motivos de consulta más frecuentes fueron la disnea (24% de los casos) y el síndrome constitucional (23%). Hasta el 30% de los casos presentaba una radiografía de tórax normal a su ingreso. Sólo en el 46% de los casos se sospechó la tuberculosis previa al fallecimiento y en el 61% fue ésta la causa del éxitus. El 52% presentaba una tuberculosis pulmonar, el 28% una tuberculosis miliar y el 20% extrapulmonar. El órgano más frecuentemente afectado fue el pulmón. En los 92 casos se encontraron granulomas epitelioides. Conclusiones. La tuberculosis es en España una causa poco frecuente de muerte en la autopsia. La presencia de sintomatología inespecífica, la escasa rentabilidad de las pruebas diagnósticas y el fallecimiento precoz hacen que un importante porcentaje de casos de tuberculosis lleguen sin diagnóstico a la necropsia (AU)

Background and objective. Tuberculosis is an infectious disease currently having great importance in the daily clinical practice in Spain. Some cases of active tuberculosis are not identified until after the patient had died and an autopsy has been performed. This study has analyzed the clinical and pathological characteristics of patients diagnosed with active tuberculosis in the autopsy. Material and method. We reviewed all the autopsies performed in the University Hospital 12 de Octubre of Madrid between 1974 and 2002. The autopsy reports and clinical records were examined in those cases in which active tuberculosis was found. Results. We found 92 cases of active tuberculosis, 57% corresponding to men. Mean age of this group was 64 years. A total of 20% of the patients died within 48 hours after admission. Predisposing factors were identified in 90% of the cases. Dyspnea (24% of cases) and wasting syndrome (23%) were the main symptoms that motivated patients to request medical attention. Up to 30% of cases had normal chest X-ray. Tuberculosis was suspected in only 46% of patients before death. Principal cause of death was tuberculosis in 61% of patients, 52% of patients had pulmonary tuberculosis, 28% suffered from miliary tuberculosis and 20% from extra-pulmonary tuberculosis. The lungs were the most frequently affected organ. Epithelioid granulomas were found in all patients. Conclusions. Tuberculosis is an uncommon finding in the autopsy as the cause of death. The presence of unspecific symptomatology, insufficient cost-effectiveness of the diagnostic tests and precocious death, are identified as the most frequent causes of undiagnosed tuberculosis (AU)

Metástasis peritoneales en el cáncer de mama: un patrón típico de diseminación del carcinoma lobulillar infiltrante / Peritoneal metastasis in breast cancer: a typical dissemination pattern of infiltrative lobular carcinoma

- Propósito: Descripción del patrón característico de disemimación metastática peritoneal del carcinoma lobulillar infiltrante de mama.- Material y métodos: Describimos tres casos de carcinomatosis peritoneal secundaria a la diseminación metastática de carcinoma lobulillar infiltrante de mama. Dos de nuestras pacientes fueron diagnosticadas de carcinomatosis peritoneal como primera manifestación de un carcinoma lobulillar de mama, y la tercera diesiciete años después de su diagnóstico inicial. - Discusión: Las metástasis peritoneales en una paciente con un carcinoma de mama son poco frecuente, pero cuando aparecen suelen ser secundarias a un carcinoma lobulillar infiltrante de mama con receptores hormonales positivos. La inespecificidad de los síntomas junto a un intervalo normalmente largo, incluso de años después de un diagnóstico inicial del tumor, hace difícil diferenciar desde el punto de vista clínico entre un tumor primario de la cavidad peritoneal o la presencia de metástasis de un carcinoma de mama. Este diagnóstico se vuelve aún más complicado cuando la lesión metastática peritoneal es la primera manifestación del cáncer de mama, como ocurrió en dos de nuestras pacientes. Los estudios de inmunohistoquímica pueden ser útiles para lograr un diagnóstico correcto. Los marcadores más informativos son la proteína 15 del flujo de los quistes mamarios (GCDFP-15:gross cystic disease fluid protein-15), y los receptores de estrógeno y progesterona. La identificación de esta entidad es importante para el oncólogo, condiciona el pronóstico y la elección de modalidades terapéuticas adecuadas que difieren a la de otros tumores que también pueden cursar con carcinomatosis peritoneal en su evolución. La quimioterapia y sobre todo la hormonoterapia, tanto los antiestrógenos como los inhibidores de la enzima aromatasa, en tumores con receptores hormonales positivos, puede ser efectiva con remisiones parciales o completas del tumor, que en algunos casos son prolongadas en el tiempo (AU)