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Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants
Thoracic Cancer ( IF 2.3 ) Pub Date : 2023-12-13 , DOI: 10.1111/1759-7714.15168 Yuta Ohishi 1 , Yoko Nakanishi 2 , Yukari Hirotani 2 , Atsuko Suzuki 3 , Tomoyuki Tanino 2 , Haruna Nishimaki-Watanabe 2 , Hiroko Kobayashi 2 , Fumi Nozaki 2 , Sumie Ohni 2 , Xiaoyan Tang 2 , Kentaro Hayashi 4 , Yoshiko Nakagawa 4 , Tetsuo Shimizu 4 , Ichiro Tsujino 4 , Noriaki Takahashi 4 , Yasuhiro Gon 4 , Shinobu Masuda 2
Thoracic Cancer ( IF 2.3 ) Pub Date : 2023-12-13 , DOI: 10.1111/1759-7714.15168 Yuta Ohishi 1 , Yoko Nakanishi 2 , Yukari Hirotani 2 , Atsuko Suzuki 3 , Tomoyuki Tanino 2 , Haruna Nishimaki-Watanabe 2 , Hiroko Kobayashi 2 , Fumi Nozaki 2 , Sumie Ohni 2 , Xiaoyan Tang 2 , Kentaro Hayashi 4 , Yoshiko Nakagawa 4 , Tetsuo Shimizu 4 , Ichiro Tsujino 4 , Noriaki Takahashi 4 , Yasuhiro Gon 4 , Shinobu Masuda 2
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The possibility of stratifying patients according to differences in ROS proto-oncogene 1 (ROS1) fusion partners has been discussed. This study aimed to clarify the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases who had different responses to crizotinib. Cytology and pathology samples from two NSCLC cases with SDC4::ROS1 who were diagnosed and treated with crizotinib at Nihon University Itabashi Hospital were obtained. Case 1 has been well-controlled with crizotinib for over 5 years, but case 2 was worse and overall survival was 19 months. Sequencing analysis of ROS1 fusion genes was performed by reverse-transcription-PCR and Sanger's sequencing methods. In addition, thyroid transcription factor (TTF)-1, ROS-1, Ki67, and phosphorylated extracellular signal-regulated kinase (pERK)1/2 expression were investigated using immunohistochemistry. Sequencing analysis showed SDC4 exon2::ROS1 exon 32 (exon33 deleted) in case 1, and coexistence of SDC4 exon2::ROS1 exon 34 and SDC4 exon2::ROS1 exon35 in case 2. The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same.
中文翻译：
克唑替尼治疗两名具有 SDC4::ROS1 融合变异的非小细胞肺癌患者的不同效果
已经讨论了根据ROS 原癌基因 1 ( ROS1 ) 融合伴侣的差异对患者进行分层的可能性。本研究旨在阐明对克唑替尼有不同反应的两例SDC4::ROS1阳性 NSCLC 病例之间的临床病理差异。获得了在日本大学板桥医院诊断并接受克唑替尼治疗的两例携带SDC4::ROS1的 NSCLC 病例的细胞学和病理学样本。病例 1 使用克唑替尼后病情得到良好控制超过 5 年，但病例 2 情况更糟，总生存期为 19 个月。通过逆转录PCR和Sanger测序方法对ROS1融合基因进行测序分析。此外，还使用免疫组织化学研究了甲状腺转录因子 (TTF)-1、ROS-1、Ki67 和磷酸化细胞外信号调节激酶 (pERK)1/2 的表达。测序分析显示病例1为SDC4 exon2:: ROS1 exon 32（exon33缺失），病例2为SDC4 exon2:: ROS1 exon 34和SDC4 exon2:: ROS1 exon35共存。Ki67指数无差异，但ROS1和pERK1不同病例2的肿瘤细胞中/2表达水平往往高于病例1。ROS1重排NSCLC中克唑替尼的治疗反应和患者预后可能与ROS1信号传导的激活有关，具体取决于ROS1和pERK1/2的过表达状态，即使ROS1融合伙伴是相同的。
更新日期：2023-12-13
中文翻译：
克唑替尼治疗两名具有 SDC4::ROS1 融合变异的非小细胞肺癌患者的不同效果
已经讨论了根据ROS 原癌基因 1 ( ROS1 ) 融合伴侣的差异对患者进行分层的可能性。本研究旨在阐明对克唑替尼有不同反应的两例SDC4::ROS1阳性 NSCLC 病例之间的临床病理差异。获得了在日本大学板桥医院诊断并接受克唑替尼治疗的两例携带SDC4::ROS1的 NSCLC 病例的细胞学和病理学样本。病例 1 使用克唑替尼后病情得到良好控制超过 5 年，但病例 2 情况更糟，总生存期为 19 个月。通过逆转录PCR和Sanger测序方法对ROS1融合基因进行测序分析。此外，还使用免疫组织化学研究了甲状腺转录因子 (TTF)-1、ROS-1、Ki67 和磷酸化细胞外信号调节激酶 (pERK)1/2 的表达。测序分析显示病例1为SDC4 exon2:: ROS1 exon 32（exon33缺失），病例2为SDC4 exon2:: ROS1 exon 34和SDC4 exon2:: ROS1 exon35共存。Ki67指数无差异，但ROS1和pERK1不同病例2的肿瘤细胞中/2表达水平往往高于病例1。ROS1重排NSCLC中克唑替尼的治疗反应和患者预后可能与ROS1信号传导的激活有关，具体取决于ROS1和pERK1/2的过表达状态，即使ROS1融合伙伴是相同的。
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