Feasibility of two-step approach for screening NTRK fusion in two major subtypes of non-small cell lung cancer within a large cohort

IF 2.7 2区医学 Q2 PATHOLOGY

Human pathology Pub Date : 2024-06-10 DOI:10.1016/j.humpath.2024.06.003

Kun Dong, Yanli Zhu, Xinying Liu, Wei Sun, Xin Yang, Kaiwen Chi, Ling Jia, Xinting Diao, Xiaozheng Huang, Lixin Zhou, Dongmei Lin

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引用次数: 0

Abstract

Our objective is to investigate a cost-effective approach to screen for NTRK fusion in the major subtypes of non-small cell lung cancer (NSCLC). Evaluate the concordance between immunohistochemistry (IHC) and next-generation sequencing (NGS), as well as between fluorescence in situ hybridization (FISH) and NGS, to detect any discrepancies in methodological consistency between lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC). Analyze the factors influencing IHC results. A cohort of 1654 patients with NSCLC underwent screening for NTRK fusion using whole slide IHC. The positive cases were analyzed by both FISH and NGS. Totally, 57 tested positive for pan-TRK, with positivity rates of 0.68% (10/1467) for LADC and 29.01% (47/162) for LSCC. FISH showed separate NTRK1 and NTRK3 rearrangements in two pan-TRK-positive LADCs, while all LSCCs tested negative. NGS confirmed functional NTRK fusion in two FISH-positive cases: one involving TPM3-NTRK1 and the other involving SQSTM1-NTRK3. A non-functional fusion of NTRK2-XRCC1 was detected in LSCC, while FISH was negative. According to our approach, the prevalence of NTRK fusion in NSCLC is 0.12%. The concordance rate between IHC and RNA-based NGS was 20% (2/10) in LADC and 0% (0/162) in LSCC. When the positive criteria increased over 50% of tumor cells showing strong staining, the concordance would be 100% (2/2). A concordance rate of 100% (2/2) was observed between FISH and RNA-based NGS in LADC. The expression of pan-TRK was significantly correlated with the tumor proportion score (TPS) of PD-L1 (p < 0.05) and transcript per million (TPM) values of NTRK2 (p < 0.05). We recommend using IHC with strict criteria to screen NTRK fusion in LADC rather than LSCC, confirmed by RNA-based NGS directly. When the NGS results are inconclusive, FISH validation is necessary.

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在大型队列中筛查非小细胞肺癌两大亚型中 NTRK 融合的两步法的可行性

我们的目标是研究一种具有成本效益的方法，用于筛查非小细胞肺癌（NSCLC）主要亚型中的 NTRK 融合。评估免疫组织化学（IHC）和新一代测序（NGS）之间以及荧光原位杂交（FISH）和 NGS 之间的一致性，以发现肺腺癌（LADC）和肺鳞癌（LSCC）在方法一致性方面的差异。分析影响 IHC 结果的因素。对 1654 例 NSCLC 患者进行了全切片 IHC NTRK 融合筛查。对阳性病例进行了 FISH 和 NGS 分析。共有 57 例检测出泛 TRK 阳性，LADC 阳性率为 0.68%（10/1467），LSCC 阳性率为 29.01%（47/162）。FISH显示，两例泛TRK阳性LADC中分别存在NTRK1和NTRK3重排，而所有LSCC的检测结果均为阴性。NGS 证实了两个 FISH 阳性病例中的 NTRK 功能性融合：一个涉及 TPM3-NTRK1，另一个涉及 SQSTM1-NTRK3。在 LSCC 中检测到了 NTRK2-XRCC1 的非功能性融合，而 FISH 呈阴性。根据我们的方法，NSCLC中NTRK融合的发生率为0.12%。在 LADC 中，IHC 与基于 RNA 的 NGS 的吻合率为 20%（2/10），在 LSCC 中为 0%（0/162）。当显示强染色的肿瘤细胞的阳性标准增加到 50%以上时，吻合率将达到 100%（2/2）。在 LADC 中，FISH 和基于 RNA 的 NGS 的一致性为 100%（2/2）。泛TRK的表达与PD-L1的肿瘤比例评分（TPS）（P＜0.05）和NTRK2的百万转录本（TPM）值（P＜0.05）显著相关。我们建议使用具有严格标准的 IHC 筛查 LADC 中的 NTRK 融合，而非 LSCC，并直接通过基于 RNA 的 NGS 确认。当 NGS 结果不确定时，有必要进行 FISH 验证。

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来源期刊

Human pathology 医学-病理学

CiteScore

5.30

自引率

6.10%

发文量

206

审稿时长

21 days

期刊介绍： Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.