RESUMO
Multiplexed analysis of multiple biomarkers in a tissue sample requires use of reporter dyes with specific spectral properties that enable discrimination of signals. Conventional chromogens with broad absorbance spectra, widely used in immunohistochemistry (IHC), offer limited utility for multiplexed detection. Many dyes with narrow absorbance spectra, eg rhodamines, fluoresceins, and cyanines, potentially useful for multiplexed detection are well-characterized; however, generation of a chromogenic reagent useful for IHC analysis has not been demonstrated. Studies reported herein demonstrate utility of tyramine-chemistry for synthesis of a wide variety of new chromogenic dye conjugates useful for multiplexed in situ analysis using conventional light microscopes. The dyes, useful individually or in blends to generate new colors, provide signal sensitivity and dynamic range similar to conventional DAB chromogen, while enabling analysis of co-localized biomarkers. It is anticipated that this new paradigm will enable generation of a wide variety of new chromogens, useful for both research and clinical biomarker analysis that will benefit clinicians and patients.
Assuntos
Biomarcadores/análise , Compostos Cromogênicos/química , Corantes/química , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , 3,3'-Diaminobenzidina/química , Biomarcadores/química , Compostos Cromogênicos/síntese química , Corantes/síntese química , Humanos , Modelos Químicos , Estrutura Molecular , Reprodutibilidade dos Testes , Tiramina/químicaRESUMO
Recurrent prostate cancer following primary treatment is common, and the population of men with biochemical recurrence is complex. Conventional management of recurrent prostate cancer involves nontargeted and/or systemic therapies, without defining an individual patient's specific disease. However, recent advances in imaging enable a shift in the management of recurrent prostate cancer to targeted, patient-specific approaches. Specifically, MRI can detect and define local prostate cancer recurrence early in the course of disease, and prostate-specific PET imaging greatly improves nodal staging and can detect previously unknown distant metastases. The significant advances in the imaging of both local and distant tumor recurrences allows for specific selection of treatment options tailored to patients and their disease with less associated morbidity.