Analysis of Predictive Biomarkers in Patients With Lung Adenocarcinoma From Southern Brazil Reveals a Distinct Profile From Other Regions of the Country.

PURPOSE: Adenocarcinoma is the most common histologic subtype of non-small-cell lung cancer, representing 40% of all diagnoses. Several biomarkers are currently used to determine patient eligibility for targeted treatments, including analysis of molecular alterations in EGFR and ALK, as well as programmed death-ligand 1 (PD-L1) protein expression. Epidemiologic data reporting the frequency of these biomarkers in Brazilian patients with lung adenocarcinoma (LUAD) are limited, and existing studies predominantly included patients from the southeast region of the country. MATERIALS AND METHODS: The goal of this study was to investigate the frequency of somatic mutations in the EGFR, KRAS, NRAS, and BRAF genes, ALK, and PD-L1 expression in a series of Brazilian patients diagnosed with LUAD predominantly recruited from centers in southern Brazil. Molecular analysis of the EGFR, KRAS, NRAS, and BRAF genes was performed by next-generation sequencing using DNA extracted from tumor tissue. Immunohistochemistry was used to detect ALK and PD-L1 expression. RESULTS: Analysis of 619 tumors identified KRAS mutations in 189 (30.2%), EGFR mutations in 120 (19.16%), and BRAF mutations in 19 (3%). Immunohistochemistry demonstrated ALK and PD-L1 expression in 4% and 35.1% of patients, respectively. CONCLUSION: To our knowledge, this is the first study investigating the molecular epidemiology of patients with LUAD from southern Brazil and the largest assessing the frequency of multiple predictive biomarkers for this tumor in the country. The study also reveals a distinct mutation profile compared with data originating from other regions of Brazil.

P53 and BCL-2 as prognostic markers in endometrial carcinoma.

The objective of this study was to verify the frequency of p53 and BCL-2 immunohistochemical expression in patients with endometrial carcinoma and to correlate it with histological factors (histological type, tumor grade, depth of myometrial invasion, lymph node involvement and surgical staging) and survival. Forty-eight patients with endometrial carcinoma who were submitted to primary surgical treatment were assessed. p53 and BCL-2 immunohistochemical expression was determined using paraffin blocks containing the tumor area. p53 and BCL-2 expression was detected in 39.6% and 58.3% of the tumors, respectively. No significant difference was found regarding the frequency of p53 expression when analyzing histological type (33.3% in endometrioid tumors, 58.3% in non-endometrioid tumors; p = 0.176), depth of myometrial invasion (p = 0.632) and surgical staging (I-11.1%, II-66.7%, III-57.1%; p = 0.061). p53 expression was significantly more frequent in undifferentiated tumors (p = 0.007) and in those showing lymph node involvement (p = 0.030). Univariate analysis showed a positive association with death (RR, 3.358; CI, 1.386-8.134; p = 0.005) and short-term survival. The present study did not reveal any correlation between BCL-2 expression and histopathologic markers or survival. In conclusion, this study showed that p53 expression is directly correlated with undifferentiated tumors, lymph-node involvement and risk of death. On the other hand, BCL-2 expression was not correlated with any known histological factors.

Clinical outcomes of eradication of Helicobacter pylori in nonulcer dyspepsia in a population with a high prevalence of infection: results of a 12-month randomized, double blind, placebo-controlled study.

Ninety-one Helicobacter pylori-positive patients with nonulcer dyspepsia were randomized to receive either lansoprazole, amoxicillin, and clarithromycin or lansoprazole and placebo. A validated questionnaire assessed dyspeptic symptoms at baseline and at 3, 6, and 12 months. Endoscopies and biopsies were performed at baseline and at 3 and 12 months. There was an overall trend, although not statistically significant, for a benefit of H. pylori eradication. Of the patients in the antibiotics group, 16 of 46 (35%) had symptomatic improvement, versus 9 of 43 (21%) in the control group (P = 0.164). In a secondary analysis, it was found that of the patients without endoscopic gastric erosions, 15 of 34 (44%) in the antibiotics group and 5 of 33 (15%) of controls had symptomatic improvement (P = 0.015). Helicobacter pylori eradication did not prove to be clinically beneficial, although a tendency to symptomatic benefit was detected. Further studies are necessary to confirm the implications of endoscopic gastric erosions in these patients.

[Clinical features in osteosarcoma and prognostic implications]. / Características clínicas do osteossarcoma na infância e sua influência no prognóstico.

OBJECTIVE: To identify the clinical features in osteosarcoma and to investigate their influence on the prognosis of children and adolescents presenting this disease. MATERIAL AND METHODS: The records of children and adolescents with osteosarcoma treated by the Bone Tumors Group of the state of Rio Grande do Sul, Brazil, between January 1992 and December 2001 were reviewed. RESULTS: Fifty consecutive patients were included in this study. Mean age at diagnosis was 13 years (3-22); 68% of the patients were males. The primary site of disease was the femur in 50% of the patients, tibia in 30%, pelvis in 4%, humerus in 10%, fibula in 2% and other sites in 4%. Nineteen patients presented metastases at diagnosis (38%). All patients received chemotherapy and were treated with three different schemes. As for surgical treatment, 26 patients (52%) had an amputation and 17 (34%) received conservative surgery. Serum lactic dehydrogenase > 1,000 UI/ml (p = 0.0159, log rank), tumor necrosis < 90% and presence of metastases had a negative influence on prognosis. The overall 5-year survival was of 33.2+/-7.2% with mean follow-up of 36 months (6-126). Event-free survival was 29.7+/-7%. The 5-year event-free survival in non-metastatic patients was 45+/-10.7%, and zero in metastatic patients (follow-up of 78.4 and 18.7 months, respectively). Only two out of 19 metastatic patients are alive and free of disease at 18 and 30 months respectively. CONCLUSION: Metastatic disease at diagnosis, serum levels of serum lactic dehydrogenase > 1,000 UI/ml and tumor necrosis < 90% are predictors of unfavorable prognosis. The excessively high incidence of metastatic patients may suggest the presence of an aggressive pattern of disease in our population, or may indicate late diagnosis.

Características clínicas do osteossarcoma na infância e sua influência no prognóstico / Clinical features in osteosarcoma and prognostic implications

OBJETIVOS: Conhecer as características clínicas e determinar os fatores de importância prognóstica de crianças e adolescentes com osteossarcoma. MATERIAIS E MÉTODOS: Foram revisados os prontuários de crianças e adolescentes com diagnóstico de osteossarcoma tratados entre janeiro de 1992 e dezembro de 2001 pelo Grupo de Tumores Osseos do Rio Grande do Sul. RESULTADOS: Foram incluídos no estudo 50 pacientes com idade mediana de 13 anos (3 a 22), sendo 68 por cento pacientes do sexo masculino. Os locais primários foram: 50 por cento fêmur, 30 por cento tíbia, 4 por cento ilíaco, 10 por cento úmero, 2 por cento fíbula e 4 por cento outros . Dezenove pacientes (38 por cento) apresentavam metástases ao diagnóstico. Todos os pacientes foram submetidos a quimioterapia. Quanto ao tratamento cirúrgico, 26 pacientes (52 por cento) foram submetidos a amputação, e 17 a cirurgia conservadora (34 por cento). A desidrogenase láctica maior do que 1.000 UI/ml ao diagnóstico, o índice de necrose inferior a 90 por cento e a presença de metástases influíram negativamente no prognóstico. A probabilidade de sobrevida global em 5 anos foi de 33,2+7,2 por cento, com média de follow-up de 36 meses (6-126); a probabilidade de sobrevida livre de eventos em 5 anos foi de 29,7+7 por cento. A probabilidade de sobrevida livre de eventos em 5 anos dos pacientes não-metastáticos ao diagnóstico foi de 45+10,7 por cento, e a dos metastáticos foi zero (médias de follow-up de 78,4 e 18,7 meses, respectivamente); apenas dois dos 19 pacientes com doença metastática encontram-se fora de tratamento e livres de doença, com follow-up de 18 e 30 meses, respectivamente. CONCLUSAO: A presença de doença metastática e nível sérico de desidrogenase láctica acima de 1.000 UI/ml ao diagnóstico, assim como índice de necrose < 90 por cento, representam fatores prognósticos desfavoráveis. O percentual excessivamente elevado de pacientes com doença metastática ao diagnóstico sugere que se trata de uma população de pacientes com doença biologicamente agressiva ou diagnosticados tardiamente em nosso meio.