Comparison of immunohistochemistry with PCR for assessment of ER, PR, and Ki-67 and prediction of pathological complete response in breast cancer

Background: Proliferation may predict response to neoadjuvant therapy of breast cancer and is commonly assessed by manual scoring of slides stained by immunohistochemistry (IHC) for Ki-67 similar to ER and PgR. This method carries significant intra- and inter-observer variability. Automatic scoring of Ki-67 with digital image analysis (qIHC) or assessment of MKI67 gene expression with RT-qPCR may improve diagnostic accuracy. Methods: Ki-67 IHC visual assessment was compared to the IHC nuclear tool (AperioTM) on core biopsies from a randomized neoadjuvant clinical trial. Expression of ESR1, PGR and MKI67 by RT-qPCR was performed on RNA extracted from the same formalin-fixed paraffin-embedded tissue. Concordance between the three methods (vIHC, qIHC and RT-qPCR) was assessed for all 3 markers. The potential of Ki-67 IHC and RT-qPCR to predict pathological complete response (pCR) was evaluated using ROC analysis and non-parametric Mann-Whitney Test. Results: Correlation between methods (qIHC versus RT-qPCR) was high for ER and PgR (spearman´s r = 0.82, p < 0.0001 and r = 0.86, p < 0.0001, respectively) resulting in high levels of concordance using predefined cut-offs. When comparing qIHC of ER and PgR with RT-qPCR of ESR1 and PGR the overall agreement was 96.6 and 91.4%, respectively, while overall agreement of visual IHC with RT-qPCR was slightly lower for ER/ESR1 and PR/PGR (91.2 and 92.9%, respectively). In contrast, only a moderate correlation was observed between qIHC and RT-qPCR continuous data for Ki-67/MKI67 (Spearman’s r = 0.50, p = 0.0001). Up to now no predictive cut-off for Ki-67 assessment by IHC has been established to predict response to neoadjuvant chemotherapy. Setting the desired sensitivity at 100%, specificity for the prediction of pCR (ypT0ypN0) was significantly higher for mRNA than for protein (68.9% vs. 22.2%). Moreover, the proliferation levels in patients achieving a pCR versus not differed significantly using MKI67 RNA expression (Mann-Whitney p = 0.002), but not with qIHC of Ki-67 (Mann-Whitney p = 0.097) or vIHC of Ki-67 (p = 0.131). Conclusion: Digital image analysis can successfully be implemented for assessing ER, PR and Ki-67. IHC for ER and PR reveals high concordance with RT-qPCR. However, RT-qPCR displays a broader dynamic range and higher sensitivity than IHC. Moreover, correlation between Ki-67 qIHC and RT-qPCR is only moderate and RT-qPCR with MammaTyper® outperforms qIHC in predicting pCR. Both methods yield improvements to error-prone manual scoring of Ki-67. However, RT-qPCR was significantly more specific

Os adolescentes infratores e o empobrecimento da rede social quando do retorno à comunidade Adolescent transgressors and the weakening of their social network when they return to the community

O objetivo deste estudo foi compreender o sucesso ou não do cumprimento da medida de ICPAE (Interno com Possibilidade de Atividade Externa) na Fase-RS (Fundação de Atendimento Sócio-Educativo do Rio Grande do Sul), à luz das características da rede social desses jovens infratores, bem como da percepção do funcionamento de sua família. Foram investigados quatro adolescentes, no começo e ao final do cumprimento desta medida, através da metodologia de estudo de caso. Utilizou-se o mapa da rede social e, para a avaliação do funcionamento familiar, foi utilizada a escala GARF (Global Assessment of Relational Functioning Scale). Houve uma tendência geral de empobrecimento da rede social desses jovens em relação ao primeiro mapa, bem como de centralização na família. A segunda avaliação do cumprimento da medida de ICPAE teve uma piora significativa em relação à primeira, excetuando-se o adolescente que teve a rede social mais completa, em ambos os momentos.<br>The goal of this case study was to understand the success (or failure) of the ICPAE initiative (from Portuguese: Intern with possibility of External Activity) of the Foundation for Social-Educative Services of Rio Grande do Sul in the light of the characteristics of the social network of these young transgressors and of their perception of the functioning of their family. Five adolescents were investigated in the beginning and in the end of the ICPAE experience. We used a social network map, and for evaluating the functioning of the family we used the GARF scale (Global Assessment of Relational Functioning Scale). It was observed that the social network of these youths tended to be poorer than in the first map and also that they were centered on the family. The second ICPAE assessment revealed significantly worse results in comparison to the first, except in the case of one adolescent who had the most complete social network in both moments