非小细胞肺癌中 ALK 重排的鉴定和治疗评估。
Identification and therapeutic evaluation of ALK rearrangements in non-small-cell lung cancer.
机构信息
Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China.
Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, PR China.
出版信息
J Pathol Clin Res. 2022 Nov;8(6):538-549. doi: 10.1002/cjp2.289. Epub 2022 Jul 18.
This study aimed to present a comprehensive assessment of anaplastic lymphoma kinase (ALK) rearrangements evaluated by DNA/RNA-based next-generation sequencing (NGS) and Ventana immunohistochemistry (IHC) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the therapeutic outcomes of ALK tyrosine kinase inhibitor (TKI) treatment. We investigated ALK gene fusions in 14,894 patients with NSCLC using Ventana IHC and NGS, including 12,533 cases detected via DNA-based NGS and 2,361 cases using RNA-based NGS. The overall percentage agreement (OPA), positive percentage agreement (PPA), and negative percentage agreement (NPA) were calculated when comparing the results between NGS and IHC. The therapeutic responses to ALK-TKIs were also evaluated. In total, 3.50% (439/12,533) of specimens were NGS ALK-positive (NGS-p) in the DNA-based NGS cohort and 3.63% (455/12,533) were IHC ALK-positive (IHC-p). The OPA of NGS was 99.60%, whereas its PPA and NPA were 92.75 and 99.86%, respectively. In the adenocarcinoma (ADC) subcohort, the PPA was 95.69%. In the RNA-based NGS cohort, 2.20% (52/2,361) of specimens were NGS-p and 2.63% (62/2,361) were IHC-p. The OPA of NGS was 99.49%; its PPA and NPA were 82.26 and 99.96%, respectively. Thirteen patients with discordant results received ALK-TKI treatment. In the seven NGS-p/IHC-negative (IHC-n) patients, the overall response rate (ORR) was 85.4% (6/7) and the disease control rate (DCR) was 100%. In the six NGS-negative/IHC-p patients, the ORR was 66.7% (4/6) and the DCR was 100%. In summary, a high concordance of ALK gene fusion detected via NGS and IHC was observed in this study. DNA-based NGS had a higher OPA, PPA, and PPA in the ADC subcohort, whereas RNA-based NGS had a higher NPA. Overall, the results suggest that the combination of NGS and IHC can improve the accuracy of ALK fusion detection; hence, a result determination algorithm for clinical detection of ALK gene fusion was also proposed.
本研究旨在全面评估非小细胞肺癌（NSCLC）患者中基于 DNA/RNA 的下一代测序（NGS）和 Ventana 免疫组织化学（IHC）检测到的间变性淋巴瘤激酶（ALK）重排，并评估 ALK 酪氨酸激酶抑制剂（TKI）治疗的疗效。我们使用 Ventana IHC 和 NGS 检测了 14894 例 NSCLC 患者的 ALK 基因融合，其中 12533 例通过 DNA 基 NGS 检测，2361 例通过 RNA 基 NGS 检测。当比较 NGS 和 IHC 的结果时，计算了总体百分比一致性（OPA）、阳性百分比一致性（PPA）和阴性百分比一致性（NPA）。还评估了对 ALK-TKI 的治疗反应。在 DNA 基 NGS 队列中，3.50%（439/12533）的标本为 NGS ALK 阳性（NGS-p），3.63%（455/12533）的标本为 IHC ALK 阳性（IHC-p）。NGS 的 OPA 为 99.60%，而其 PPA 和 NPA 分别为 92.75%和 99.86%。在腺癌（ADC）亚组中，PPA 为 95.69%。在 RNA 基 NGS 队列中，2.20%（52/2361）的标本为 NGS-p，2.63%（62/2361）的标本为 IHC-p。NGS 的 OPA 为 99.49%；其 PPA 和 NPA 分别为 82.26%和 99.96%。有 13 名结果不一致的患者接受了 ALK-TKI 治疗。在 7 名 NGS-p/IHC-阴性（IHC-n）患者中，总缓解率（ORR）为 85.4%（6/7），疾病控制率（DCR）为 100%。在 6 名 NGS 阴性/IHC-p 患者中，ORR 为 66.7%（4/6），DCR 为 100%。综上所述，本研究观察到 NGS 和 IHC 检测到的 ALK 基因融合具有很高的一致性。DNA 基 NGS 在 ADC 亚组中具有更高的 OPA、PPA 和 PPA，而 RNA 基 NGS 具有更高的 NPA。总体而言，结果表明 NGS 和 IHC 的结合可以提高 ALK 融合检测的准确性；因此，还提出了一种用于临床检测 ALK 基因融合的结果确定算法。
Zotero 插件