Abstract #5394: MicroRNA-based assay for differential diagnosis of squamous from non-squamous non small cell lung carcinoma

Background: Lung cancer is the leading cause of cancer mortality in the USA. Recent advances in biologically directed therapies for non-small cell lung carcinoma (NSCLC) emphasize the need for more accurate sub-classification of NSCLC, as treatment may be dictated by histologic subtype. In particular, squamous histology can be a counter-indication for treatment by VEGF inhibitors. MicroRNAs are involved in a variety of biological and pathological processes, and have been demonstrated to be highly tissue-specific biomarkers with potential clinical applicability for defining cancer type and origin. MicroRNAs are well preserved in formalin fixed tissue, making them ideal candidates for molecular markers for use in routinely processed material. Here we report on the development and performance of a microRNA-based assay for the differential diagnosis of squamous from non-squamous NSCLC. Methods: The first phase compared microRNA expression profiles for hundreds of microRNAs in more than a hundred samples of squamous and adenocarcinomas of the lung. This screen identified a strong squamous-specific biomarker, that was verified by qRT-PCR in additional samples. A diagnostic assay was developed that utilized microRNA qRT-PCR to measure the normalized level of this marker in FFPE samples. The performance of this assay was assessed in an independent, blinded test set. Results: The microRNA-based assay that was developed reached sensitivity and specificity exceeding 90% in the identification of squamous cell lung carcinomas in an independent blinded validation set. Conclusions: MicroRNAs are becoming an important tool for classification of cancers. A diagnostic assay based on the specificity of a single microRNA accurately identifies squamous from non-squamous NSCLC. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5394.