Germline and Somatic mutations in postmenopausal breast cancer patients

OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Anticorpos contra citoplasma de neutrófilos (ANCA) em portadores vasculites / Antibodies against neutrophil cytoplasm (ANCA) in bearing of vasculitis

A granulomatose de Wegener é uma vasculite sistêmica cujo diagnóstico se baseia em dados clínicos, radiológicos e histopatológicos. Recentemente foi descrito nesses pacientes a presença de anticorpos contra citoplasma de neutrófilos normais (ANCA) e sua detecçäo seria de valor no diagnóstico e na avaliaçäo de atividade de doença. Estudamos a freqüência desses anticorpos utilizando técnicas de ELISA e imunofluorescência indireta (IFI) em 103 pacientes com vasculites primárias ou secundárias a doenças difusas do tecido conjuntivo. Observamos positividade do ANCA por IFI em sete de 17 pacientes com granulomatose de Wegener (GW), quatro de 24 portadores de PAN, sendo que três desses apresentaram padräo atípico de IF, houve positividade microscópica e um paciente, vasculite näo caracterizada. Pela técnica de ELISA, houve positividade do ANCA em cinco de 24 casos de PAN, quatro de 17 casos de GW, um de 16 casos de polimialgia reumática, um caso de arterite microscópica e em uma, vasculite näo determinada. Esses dados confirmam o valor da detecçäo do ANCA em vasculites sistêmicas primárias, particularmente a GW

Anticorpos anticardiolipina em vasculites / Antiocardiolipin antibodies in vasculitis

Os autores estudaram os anticorpos anticardiolipina (aCL) em pacientes com vasculites. Esses anticorpos foram detectados em seis de 15 pacientes com vasculite reumatóide, três de 29 com poliarterite nodosa, dois de nove com síndrome de Behcet, dois de quatro com arterite de células gigantes, um de seis com vasculite de Churg-Strauss e nenhum dos pacientes com granulomatose de Wegener ou púrpura de Henoch-Schönlein. Os autores discutem os possíveis mecanismos patogênicos desses anticorpos