A new molecular analysis tool has been used to detect the level of an important target for immunotherapy in early-stage breast cancers, researchers at Yale University report in the journal Clinical Cancer Research (Clin Cancer Res; 20(10); 2773 82).
Blockade of the PD-1/PD-L1 pathway is an important axis for new oncology therapies against melanoma, breast, ovarian, colorectal and other cancers. Levels of tumour PD-L1 expression are indicative of tumour survival and response to treatment. Development of accurate reproducible PD-L1 test is imperative in the pharmaceutical and R&D healthcare setting. However measurement of PD-L1 protein levels is limited by lack of standardisation of tests and variable performance of antibodies.
The new diagnostic test, developed in the Rimm laboratory at Yale University Department of Pathology using RNAScope, measures the amount of PD-L1 mRNA in cancer tissues. It is devoid of many of the technical issues that plague antibody-based detection methods that have yielded conflicting results in the past. In their published study analysing PD-L1 mRNA in 636 breast cancers, nearly 60% of tumours were positive for PD-L1 mRNA. Furthermore, PD-L1 mRNA levels are significantly associated with tumour infiltrating lymphocytes, breast cancer ER negative status and improved recurrence free survival.
These observations support the evaluation of PD-1/PD-L1 targeted therapies in breast cancer and offer new hope for the development of a robust clinical test for patient stratification.
Source: K. A. Schalper, V. Velcheti, D. Carvajal, H. Wimberly, J. Brown, L. Pusztai, D. L. Rimm. In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clinical Cancer Research, 2014; 20 (10): 2773 DOI: 10.1158/1078-0432.CCR-13-2702
Pathology Diagnostics Ltd (pathologydiagnostics.com) is an independent GCLP accredited histopathology research organisation delivering high-quality tissue laboratory & diagnostics services to industry Research & Development scientists engaged in drug and biomarker development.
Specialising in the provision of clinical diagnostics and quantitative image analysis on human tissues for studies ranging from early discovery to clinical trials, Pathology Diagnostics offers a range of services from traditional histopathology techniques to advanced digital pathology, whole slide scanning, central biorepository services and quantitative image analysis of biomarkers.