Validation of the 4B5 rabbit monoclonal antibody in determining Her2/neu status in breast cancer

HER2 overexpression in breast cancer is associated with worse clinical outcome. To select patients for anti-Her2-based therapy immunohistochemistry is commonly performed as a first step to assess Her2 status. However, interobserver and interlaboratory variability can significantly compromise adequate assessment of Her2 status. In addition, immunohistochemistry does not always result in an unambiguous test result requiring additional testing for Her2 gene amplification. This study aimed to improve the reliability of Her2 immunohistochemistry by using rabbit monoclonal antibody 4B5 as an alternative to mouse monoclonal antibody CB11 routinely used in our laboratory. Therefore, 283 breast adenocarcinomas were included in a tissue microarray. Immunohistochemistry using the 4B5 and CB11 antibodies, and fluorescence and chromogenic in situ hybridization (FISH or CISH) were performed. Immunohistochemistry was scored by two independent investigators. We found that 4B5 staining was more distinct than CB11 staining. For CB11 staining, there were 12% (BV) and 5% (JW) 2 + scores compared with 4% (BV) and 2% (JW) for 4B5. There was a strong trend towards higher interobserver agreement for 4B5 compared with CB11 (4B5: kappa 0.87, 95% CI 0.79-0.96; CB11: kappa 0.77, 95% CI 0.66-0.88). There were no significant differences in sensitivity, specificity and predictive values between CB11 and 4B5. Our results indicate that the 4B5 antibody provides more robust assessment of immunohistochemical Her2/neu status and will reduce the number of gene amplification tests compared with CB11. However, for tumours with a 2 + score additional gene amplification measurement using FISH or CISH remains necessary. Modern Pathology (2009) 22, 879-886; doi: 10.1038/modpathol.2009.37; published online 20 March 2009

Primary progressive aphasia: analisys of 16 cases Afasia progressiva primária: análise de 16 casos

Primary progressive aphasia (PPA) is an intriguing syndrome, showing some peculiar aspects that differentiate it from classical aphasic pictures caused by focal cerebral lesions or dementia. The slow and progressive deterioration of language occurring in these cases provides an interesting model to better understand the mechanisms involved in the linguistic process. We describe clinical and neuroimaging aspects found in 16 cases of PPA. Our patients underwent language and neuropsychological evaluation, magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT). We observed a clear distinction in oral expression patterns; patients were classified as fluent and nonfluent. Anomia was the earliest and most evident symptom in both groups. Neuroimaging pointed to SPECT as a valuable instrument in guiding the differential diagnosis, as well as in making useful clinical and anatomical correlations. This report and a comparison to literature are an attempt to contribute to a better understanding of PPA.<br>A afasia progressiva primária (APP) é uma síndrome que tem despertado grande interesse devido a aspectos particulares que a diferenciam das afasias clássicas (secundárias a lesões cerebrais focais) e dos quadros demenciais. A deterioração lenta e progressiva da linguagem presente nesses casos fornece um interessante modelo de observação dos mecanismos subjacentes ao processamento linguístico. Descrevemos as características clínicas e de neuroimagem de 16 casos de APP. Os pacientes foram submetidos a exame de linguagem, neuropsicológico, ressonância magnética (RM) e tomografia computadorizada por emissão de fóton único (SPECT). Clinicamente pudemos observar uma nítida distinção nos padrões de produção oral, sendo os pacientes agrupados em fluentes e não-fluentes. Anomia foi o sintoma mais precoce e evidente nos dois subgrupos. Os achados de neuroimagem permitem destacar a sensibilidade do SPECT como instrumento diagnóstico. O registro e a comparação destes casos aos da literatura são uma tentativa de contribuir para a compreensão da APP