BackgroundThe aim of this study was to compare histomorphometric changes and the results of immunohistochemical tests for VCAM, ICAM-1, CD4 and CD8 in normal placentas from HIV-seropositive pregnant women.MethodsSamples of normal placentas were divided into 2 groups: healthy HIV-seronegative pregnant women (control group = C = 60) and HIV-seropositive women (experimental group = E = 57). Conventional histological sections were submitted to morphometric analysis and evaluated in terms of the immunohistochemical expression of ICAM-1, VCAM, CD4 and CD8.ResultsThe villi in group E were smaller than those in group C. The median for the CD8+ T cell count was higher in group E than in group C (p = 0.03). Immunohistochemical expression of ICAM-1 was observed in 57% of the cases in group E, compared with 21% of those in group C (p = 0.001). There was no difference in VCAM expression or CD4+ cell counts between groups and no correlation between the data for antiretroviral therapy and morphometric or immunohistochemical data.ConclusionsThe morphometric data showed that placentas of HIV-seropositive pregnant women tend to have smaller villi than those of seronegative women. In addition, immunohistochemical testing for infectious agents helped to identify cases that were positive for microorganisms (6/112) that routine pathological examination had failed to detect. The anti-p24 antibody had a limited ability to detect HIV viral protein in this study (2/57). Correlation of immunohistochemical expression of CD8+ T cells and ICAM-1 with the presence of HIV in the placenta revealed that those expressions can act as biomarkers of inflammatory changes. There was no correlation between the data for antiretroviral therapy and morphometric or immunohistochemical data.
Objectives: Approximately 60% of lung adenocarcinomas (LAs) carry mutations that can guide treatment with tyrosine-kinase inhibitors (TKI) and other targeted therapies. Data on activating mutations in EGFR and other tyrosine-kinase receptor (TKR) genes in highly admixed populations, such as that of Brazil, are scarce. In this study, we comprehensively analyzed the actionable alteration profile of LA in Brazilian patients. Materials and Methods: EGFR driver mutation data were collected from a large Brazilian LA cohort covering an 8-year period of molecular testing in a single institution. Tests were performed using three distinct methods, and demographic and histopathological data were analyzed. For a subset of patients, driver mutations in KRAS, NRAS, and BRAF and gene fusions involving TKR genes (before TKI treatment) and EGFR T790M (after TKI treatment) were assessed. Results: EGFR mutations were detected in 25% of 1,316 LAs evaluated, with exon 19 deletions and exon 21 L858R TKI sensitizing mutations representing 72.5% of all mutations. Mutation rates were higher in women and non-smokers (p < 0.001). Next-generation sequencing was very sensitive, with a lower rate of inconclusive results compared with Sanger sequencing and pyrosequencing. EGFR/RAS/BRAF hotspot gene panels were applied in 495 LA cases and detected oncogenic mutations in 51.3% of samples, most frequently in EGFR (22.4%) and KRAS (26.9%). In subgroups of 36 and 35 patients, gene fusions were detected in 11.1% of tumors and EGFR T790M resistance mutations were detected in 59% of plasma samples from patients previously treated with TKI, respectively. Conclusion: This report provides the first comprehensive actionable alteration portrait of LA in Brazil. The high rate of actionable alterations in EGFR and other driver genes in LA reinforces the need to incorporate TKI guided by molecular diagnostics into clinical routines for patients in both public and private healthcare systems.
Introduction: We evaluated overall survival (OS) benefit of complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) using a propensity score-matched (PSM) analysis to balance groups by age, gender and by the International Metastatic RCC Database Consortium prognostic model (IMDC). Methods: We included patients (pts) treated at the AC Camargo Cancer Center between 2007 and 2016. Pairs were matched by age, gender and IMDC. Kaplan-Meier survival estimates and Cox proportional hazard models were used to evaluate OS on CM and no-CM group. Results: We found 116 pts with clear cell mRCC. After PSM, the number was reduced to 74 (37 CM, 37 no-CM). The median OS for CM and no-CM was 98.3 months and 40.5 months, respectively (hazard ratio 0.24 95%CI 0.11-0.53 p < 0.001). The OS benefit of CM was confirmed on favourable and intermediate IMDC but was absent on poor IMDC. The CM group received less systemic therapy than the no-CM group. Ten pts in the CM group still have no evidence of disease (NED). Conclusion: After matching for age, gender and IMDC, we found CM impacts on OS and also diminishes the need for systemic treatment. Survival benefit was confirmed for favourable/intermediate IMDC but not for the poor IMDC prognostic model. Further studies correlating IMDC and metastasectomy are needed to guide clinical decision-making.
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