Detection of Light Chain Restriction in non-Hodgkin Lymphoma by a Novel RNA In Si

描述（由申请人提供）： 免疫球蛋白（IG）轻链限制（LCR）检测是鉴别诊断的重要分子诊断工具，包括淋巴样增生、非典型淋巴样增生、慢性炎症和B细胞肿瘤。目前在福尔马林固定石蜡包埋（FFPE）组织中鉴定LCR的方法包括免疫组织化学（IHC）和常规显色原位杂交（CISH），分别测量κ或λ蛋白和mRNA。然而，IHC和常规CISH都缺乏足够的灵敏度来检测许多非霍奇金淋巴瘤（NHL）中的LCR，包括最常见的NHL变体-滤泡性淋巴瘤、弥漫性大B细胞淋巴瘤、小B淋巴细胞淋巴瘤和MALT型结边缘区淋巴瘤。RNAscope是一种新型的RNA原位杂交技术，具有单分子检测灵敏度，并且使用显色或荧光检测与FFPE组织完全兼容。我们假设RNAscope将准确和可重复地描绘所有非霍奇金淋巴瘤类型的LCR。我们建议开发一种基于RNAscope的CISH检测方法，用于检测FFPE组织中的LCR。 公共卫生相关性： 淋巴瘤的诊断可能是困难的基础上的形态学。限制性免疫球蛋白轻链表达的检测是一种分子辅助工具，以解决模棱两可的淋巴组织增生性疾病。基于RNAscope的拟议产品将提供比当前方法更优越的上级灵敏度。

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. Current methods of LCR identification in formalin fixed paraffin embedded (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 novel RNA in situ hybridization technology that has single-molecule detection sensitivity and is fully compatible with FFPE tissue using either chromogenic or fluorescent detection. We hypothesize that RNAscope will accurately and reproducibly delineate LCR in all non-Hodgkin lymphoma types. We propose to develop an RNAscope-based CISH assay for kappa and lambda mRNAs for LCR detection in FFPE tissue. 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 based on RNAscope will provide superior sensitivity to current methods.