ABSTRACT
Monoclonal therapies could represent baseline-personalized medicine for patients with neoplasia. One of the most successful examples is Trastuzumab, a humanized antibody against epidermal growth factor receptor 2. Human epidermal growth factor receptor 2 (HER2) is a trans-membrane tyrosine kinase coded by the gene HER2/neu and overexpressed in approximately 12% to 20% of infiltrating breast carcinomas. The overexpression of HER2 is an independent adverse prognostic factor in relation to survival and is also predictive of response to treatment. Therefore, the correct evaluation of HER2 status is essential for the management of infiltrating breast carcinoma to determine the response to Trastuzumab. The most common evaluation technique is immunohistochemistry, which is confirmed by fluorescent or chromogenic monochrome or dual-gene in situ hybridization in ambiguous cases (immunohistochemical 2+). Our objective was to evaluate the diagnostic value of a new technique on the basis of HER2 mRNA in situ hybridization (HistoSonda) and study its correlation with immunohistochemistry and dual-chromogenic in situ hybridization (DUO-CISH) in 403 cases of infiltrating breast carcinoma. The percentage of DUO-CISH amplification was 25.8%, HistoSonda positivity was 31.2%, and positivity for Hercep-Test was 48.1%, including (+2) and (+3). Comparisons were made of each of the techniques, HistoSonda to IHQ and HistoSonda to DUO-CISH. The overall concordance between DUO-CISH and HistoSonda was 89%. Our data support the consistency of HistoSonda as a useful tool to determine HER2 status in breast cancer.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , In Situ Hybridization/methods , RNA, Messenger/metabolism , Receptor, ErbB-2/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Diagnostic Errors , Female , Humans , Molecular Diagnostic Techniques , Prospective Studies , RNA, Messenger/genetics , Receptor, ErbB-2/metabolism , Retrospective Studies , SpainABSTRACT
Identifying cellular and molecular mechanisms that direct the formation of circuits during development is thought to be the key to reconstructing circuitry lost in adulthood to neurodegenerative disorders or common traumatic injuries. Here we have tested whether brain regions situated in and around the developing nigro-striatal pathway have particular chemoattractive or chemorepulsive effects on mesencephalic dopamine axons, and whether these effects are temporally restricted. Mesencephalic explants from embryonic day (E)12 rats were either cultured alone or with coexplants from the embryonic, postnatal or adult medial forebrain bundle region (MFB), striatum, cortex, brain stem or thalamus. Statistical analysis of axon growth responses revealed a potent chemoattraction to the early embryonic MFB (i.e. E12-15) that diminished (temporally) in concert with the emergence of chemoattraction to the striatum in the late embryonic period (i.e. E19+). Repulsive responses by dopaminergic axons were obvious in cocultures with embryonic brain stem and cortex, however, there was no effect by the thalamus. Such results suggest that the nigro-striatal circuit is formed via spatially and temporally distributed chemoattractive and chemorepulsive elements that: (i) orientate the circuit in a rostral direction (via brain stem repulsion); (ii) initiate outgrowth (via MFB attraction); (iii) prevent growth beyond the target region (via cortical repulsion); and (iv) facilitate target innervation (via striatal chemoattraction). Subsequent studies will focus on identifying genes responsible for these events so that their products may be exploited to increase the integration of neuronal transplants to the mature brain, or provide a means to (re)establish the nigro-striatal circuit in vivo.
