基因君官网
听说了一个重大新闻：
美国基因治疗公司Cancer Genetics采用RNAscope技术发现淋巴瘤PD-L1表达及其免疫应答的精细模式，该研究发表于第59届美国血液学会（ASH）年会。我们一起去看看吧！
Cancer Genetics advances understanding of immune response and measurement in lymphomas by combining PD-L1 expression analysis with RNA analysis
· 该研究发表于第59届美国血液学会（ASH）年会
· 该研究重点关注DLBCL（弥漫性大B细胞淋巴瘤）
· 该研究使用RNAscope技术获得精准医疗信息
转载自CGI公司网页新闻报道：
· RUTHERFORD, N.J., Dec. 11, 2017 (GLOBE NEWSWIRE) — Cancer Genetics, Inc. (Nasdaq:CGIX), a leader in enabling precision medicine for oncology through molecular markers and diagnostics, today announced results of a study demonstrating the potential value of being platform-agnostic and choosing the best diagnostic modality to evaluate an important molecular biomarker, PD-L1, in DLBCL (Diffuse Large B-Cell Lymphomas). The results (abstract 1477) were presented on Sunday, December 10, 2017 at the 59th ASH Annual Meeting in Atlanta.
新泽西州卢瑟福市2017年12月11日电（全球通社） – Cancer Genetics 公司（纳斯达克股票代码：CGIX）–分子诊断技术和肿瘤精准医疗的领导者-今天宣布了一项研究结果。该研究展示了诊断平台研究的潜在价值，筛选出了评估弥漫性大B细胞淋巴瘤中重要分子生物标志物PD-L1的最佳诊断方式。其研究结果（摘要1477）于2017年12月10日（星期日）发表于亚特兰大第59届ASH年会。
· The study compared performance of multiple antibody clones against PD-L1 and the current standard diagnostic modality, immunohistochemistry (IHC), to an in-situ hybridization (ISH), using RNAscope®1 approach to determine the expression of PD-L1 in diffuse large B-cell lymphoma (DLBCL) cells, a particularly aggressive form of lymphoma.
该研究采用RNAscope®1技术检测弥散性大B细胞淋巴瘤（高度恶性淋巴瘤）中的PD-L1，对比了PD-L1多克隆抗体免疫组化（IHC）标准诊断技术和原位杂交（ISH）技术。
· Although the two modalities demonstrated relative concordance related to the identification of PD-L1 expression, there were differences that indicated that RNA-ISH may be the superior approach. First, RNA-ISH appeared to be more sensitive, identifying cases of PD-L1 expression that were negative using IHC. Second, high PD-L1 expression identified by RNA-ISH, but not IHC, was highly correlated with non-germinal center B-cell subtype, gains at the PD-L1/9p24 locus (a predictor of PD-L1 inhibitor response) and demonstrated a trend toward worse overall survival. The study demonstrates that choice and integration of diagnostic modalities can provide key additional information to assist oncologists to more accurately select therapeutic options for their patients.
研究发现，两种方法的检测结果呈现出相对一致性，但存在一些差异，而这些差异恰巧表明使用RNAscope的RNA-ISH技术可能更好:
· 首先，RNA-ISH更敏感，能检测出IHC检测阴性结果病例中的PD-L1。
· 其次，RNA-ISH检测结果表明，PD-L1/9p24位点扩增和高表达的PD-L1（PD-L1抑制的预测因子）与非生发中心B细胞亚型以及整体生存率走低相关，而IHC检测没有体现该结果。
· 该研究表明，选择和整合正确的诊断方式，可以获得关键辅助信息，从而帮助肿瘤学家作出更加精准的治疗方案。
· “Precision oncology is all about better identifying the biomarkers in a patient’s tumor that both assist in diagnosis and drive a treatment plan tailored to the patient’s cancer with the objective of obtaining an optimal clinical outcome,” said Panna Sharma, President and CEO of Cancer Genetics. “This means that companies and laboratories in precision oncology should utilize the platform or platforms that generate the best validated information to drive treatment. This study demonstrates for a particular tumor type, DLBCL, that RNA-ISH generates superior information compared to IHC alone, which has been the standard for many years. We at Cancer Genetics would like to take this approach further to the benefit of the oncology community and the patients they treat.”
Cancer Genetics总裁兼首席执行官Panna Sharma说：“精准肿瘤学的目标是更精准地检测患者肿瘤细胞中的生物标志物，帮助诊断并制定个性化肿瘤治疗方案，以获得最佳的临床疗效”。“这意味着精准肿瘤学公司和实验室应该利用能够提供最佳验证信息的平台来推动治疗。这项研究表明，对于特定的肿瘤类型，如DLBCL，RNA-ISH技术优于使用多年的标准技术IHC，可提供更多有效信息。Cancer Genetics希望进一步使用这种诊断方法，为肿瘤学界和肿瘤患者谋利。
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Poster and Oral Presentation Title (abst 1477): Precision in PD-L1 Assessment in Diffuse Large B Cell Lymphoma: Greater Biological Insight Using in Situ Hybridization approach
Imran Siddiqi, MD PhD1*, Venkata Thodima, PhD2*, Kishor Bhatia, PhD2*, Jane Houldsworth, PhD3 and Rita Shaknovich, MD, PhD4
1University of Southern California, Los Angeles
2Cancer Genetics Inc, Rutherford, NJ
3Pathology Department, The Mount Sinai Hospital, New York, NY
4Cancer Genetics, Inc., Rutherford, NJ
PD-L1 expression in diffuse large B-cell lymphoma (DLBCL) has been associated with the activated B-cell (ABC) type, gains/ amplifications at the PD-L1/ 9p24 locus, and worse clinical outcome in the setting of conventional (R-CHOP) chemotherapy. Most of the prior studies have evaluated PD-L1 expression by immunohistochemistry (IHC), utilizing a variety of antibody clones and with various cut-offs for determining positivity. IHC methods for evaluating PD-L1 expression are inherently suboptimal due to the differing sensitivities/ specificities of the various clones and staining platforms and the lack of well-established interpretive criteria. Moreover, quantifying levels of PD-L1 expression by percent of positive cells and/or staining intensity are difficult and highly subjective. Alternative, highly sensitive and quantitative approaches for studying PD-L1 expression are available (e.g. gene expression profiling, flow cytometry), but these methods lack the ability to distinguish PD-L1 expression in lymphoma cells from those of the surrounding immune microenvironment.
RNA-based, in situ hybridization on formalin-fixed tissues is a sensitive, specific and more quantitative approach for determining levels of expression on morphologically preserved tissue. We analyzed 69 of DLBCL cases by RNAScope in situ hybridization (Advanced Cell Diagnostics) on an automated Leica platform. PD-L1 expression was quantitated in lymphoma cells using established scoring guidelines from 0 to 4 , where 0 corresponds to no RNA expression detected or only one hybridization signal and 4 corresponds to 10 or more signals per cell. From 69 cases of DLBCLs studied 45% had the score of 0, 17% score of 1, 23% score of 2, 6% score of 3 and 9% score of 4. Results were correlated with IHC (using a variety of commercial antibodies), cell of origin classification and gains/ losses at the 9p24 locus (PD-L1 locus).
We observed that PD-L1 expression quantified by RNAScope highly correlated with IHC (p<0.0001, Chi-square test) method. In the lower range of PD-L1 expression, RNAscope had higher sensitivity and dynamic range with 23 cases demonstrating no PD-L1 expression using IHC (score of 0) revealing low levels of amplification using RNAscope: with 15 cases at score 0, 7 cases at score 1 and 1 case at score 2. We also observed that high RNAScope scores categorized as high (3,4) were strongly correlated with non-GCB type and also with samples showing gain of 9p24 (p=0.0061 Chi-square test, p=0.0002, Chi-square test respectively). Interestingly, PD-L1 expression based protein detection using IHC correlated with EBV infection (p=0.008 Chi-square test), while RNAscope score demonstrated no significant correlation (p=0.6 Chi-square test). Comparison of IHC scores and RNAscope scores in EBV positive cases demonstrated that PD-L1 overexpression was not linked to 9p24 amplification, thus suggesting a different biological mechanism of PD-L1 overexpression in EBV-associated cases.
These findings shed additional light into potential mechanism of PD-L1 overexpression in DLBCLs and offer a complimentary and highly sensitive practical approach of assessing PD-L1 overexpressing tumors in FFPE tissue.
–转载自CGI公司新闻报道
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