在中国非小细胞肺癌患者中同时进行 VENTANA IHC 和 RT-PCR 检测 ALK 状态及其对克唑替尼的反应。
Simultaneous VENTANA IHC and RT-PCR testing of ALK status in Chinese non-small cell lung cancer patients and response to crizotinib.
机构信息
Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, No 420, Fuma Road, Fuzhou, 350014, Fujian, People's Republic of China.
Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, People's Republic of China.
出版信息
J Transl Med. 2018 Apr 11;16(1):93. doi: 10.1186/s12967-018-1468-9.
BACKGROUND
ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements.
METHODS
A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent.
RESULTS
Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion.
CONCLUSIONS
VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib.
背景
ALK 重排-晚期 NSCLC 患者对克唑替尼有反应。ALK 重排目前通过 RT-PCR 确定。VENTANA IHC 是识别 NSCLC 中 ALK 蛋白过表达的标准方法；然而，VENTANA IHC 很少用于确定中国 NSCLC 和 ALK 过表达患者对克唑替尼的反应。为了更好地阐明 VENTANA IHC 检测 ALK 重排的临床意义，我们进行了这项研究，以分析在接受 ALK 重排筛查的大量中国 NSCLC 患者中 VENTANA IHC 和 RT-PCR 的结果。
方法
共纳入 1720 例通过 VENTANA IHC 和/或 RT-PCR 检测到 ALK 重排的 NSCLC 患者，对 VENTANA IHC 和 RT-PCR 检测到的 ALK 阳性患者的疗效和生存进行比较。我们使用 NGS 来确定两种方法不一致的患者。
结果
在 1720 例患者中，187 例（10.87%）通过 VENTANA IHC 和/或 RT-PCR 检测到 ALK 阳性，其中 66 例接受了克唑替尼治疗。我们通过 VENTANA IHC 方法确定了 10.27%（172/1674）的患者为 ALK 阳性，通过 RT-PCR 方法确定了 12.73%（41/322）的患者为 ALK 重排。276 例 ALK 阳性患者中的 29 例同时进行了 VENTANA IHC 和 RT-PCR 分析。通过 VENTANA IHC 总缓解率为 65.90%（29/44），通过 RT-PCR 为 55.88%（19/34）。通过 VENTANA IHC 和 RT-PCR 疾病控制率分别为 86.36%（38/44）和 76.47%（26/34）。相比之下，通过 VENTANA IHC 和 RT-PCR 获得的中位无进展生存期分别为 8.5 个月和 9.2 个月。根据 NGS，在 17 例 ALK 阳性患者中，有 6 例的 VENTANA IHC 和 RT-PCR 结果不一致；具体而言，4 例患者有 EML4-ALK 融合，2 例患者有非 EML4-ALK 融合，1 例患者有 KCL1-ALK 融合，1 例患者有 FBXO36-ALK 融合。
结论
VENTANA IHC 是一种可靠且快速的筛选工具，可用于常规病理实验室识别适合接受 ALK 靶向治疗的候选者。VENTANA IHC 具有中等的敏感性，与 ALK 抑制剂治疗反应的相关性略高，一些 VENTANA IHC 阳性但 RT-PCR 阴性的病例可能受益于克唑替尼。
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