ADVANCED CELL DIAGNOSTICS, INC. — Department of Health and Human Services SBIR Phase II: 102

Description

DESCRIPTION provided by applicant Immunoglobulin Ig light chain restriction LCR detection is an important molecular diagnostic tool in the differential diagnosis that includes lymphoid hyperplasia atypical lymphoid hyperplasia chronic inflammation and B cell neoplasms LCR can be detected by flow cytometry FCM as an abnormal kappa lambda ratio on the cell surface However FCM requires fresh unfixed tissue Some B cell lymphomas lack surface Ig expression detectable by FCM some demonstrate nonspecific antibody binding Often only formalin fixed paraffin embedded FFPE tissue is available for pathologic evaluation Current methods of LCR identification in FFPE tissue include immunohistochemistry IHC and conventional chromogenic in situ hybridization CISH which measure kappa or lambda protein and mRNA respectively However both IHC and conventional CISH lack sufficient sensitivity to detect LCR in many non Hodgkin lymphoma NHL including the most common NHL variants follicular lymphoma diffuse large B cell lymphoma small B lymphocytic lymphoma and extranodal marginal zone lymphoma of MALT type RNAscope is a novel RNA in situ hybridization technology which has single molecule detection sensitivity and is fully compatible with FFPE tissue using either chromogenic or fluorescent detection We have developed a manual bright field kappa and lambda duplex RNA ISH assay for LCR which has demonstrated broad applicability to all NHL subtypes In this project we will develop a fully automated duplex RNAscope LCR assay with digital pathology interpretation which should greatly facilitate clinical adoption of this novel assay PUBLIC HEALTH RELEVANCE The diagnosis of lymphoma can be difficult based on morphology alone Detection of restricted immunoglobulin light chain expression is a molecular ancillary tool to resolve ambiguous lymphoproliferative disorders The proposed product is a fully automated RNA in situ hybridization assay for light chain mRNAs based on the RNAscope technology which will provide superior sensitivity to current methods