Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.
Pediatr Surg Int. 2021 Feb;37(2):287-291. doi: 10.1007/s00383-020-04806-w. Epub 2021 Jan 4.
The majority of relapsed neuroblastomas have mitogen-activated protein kinase (MAPK) pathway activating mutations. We previously showed the in vitro and in vivo anti-tumor effects of MAPK/ERK kinase (MEK) inhibitors in MAPK-activated neuroblastoma. We herein assessed the correlation between MAPK activation and the prognosis in neuroblastoma patients using phosphorylated extra-cellular signal-regulated kinase (pERK) immunohistochemistry to establish the protocol for the clinical administration of MEK inhibitors.
Neuroblastoma samples from patients treated in our hospital were immunostained with pERK. The clinical outcomes were retrospectively collected from medical records. The correlation between pERK positivity and the prognosis was analyzed.
Regarding pre-chemotherapeutic specimens, there were no differences in the pERK status between tumors with a good and bad prognosis in both the nuclei and cytoplasm. Regarding post-chemotherapeutic specimens, one of eight tumors with a good prognosis and four of six tumors with a poor prognosis showed pERK-positive nuclear staining (p = 0.0909) and five of eight tumors with a good prognosis and four of six tumors with a poor prognosis showed pERK-positive cytoplasmic staining (p > 0.9999).
These findings suggested post-chemotherapeutic-not pre-chemotherapeutic-nuclear pERK-positive neuroblastoma tends to be associated with a poor prognosis and may be a potential therapeutic target for MEK inhibitor treatment.
大多数复发性神经母细胞瘤具有丝裂原活化蛋白激酶（MAPK）通路激活突变。我们之前已经证明了 MAPK/ERK 激酶（MEK）抑制剂在 MAPK 激活的神经母细胞瘤中的体外和体内抗肿瘤作用。我们在此使用磷酸化细胞外信号调节激酶（pERK）免疫组化来评估 MAPK 激活与神经母细胞瘤患者预后之间的相关性，以建立 MEK 抑制剂临床给药方案。
用 pERK 对我院治疗的神经母细胞瘤样本进行免疫染色。从病历中回顾性收集临床结果。分析 pERK 阳性与预后的相关性。
关于化疗前标本，在细胞核和细胞质中，预后良好和不良的肿瘤之间的 pERK 状态没有差异。关于化疗后标本，8 个预后良好的肿瘤中有 1 个和 6 个预后不良的肿瘤中有 4 个显示 pERK 阳性核染色（p=0.0909），8 个预后良好的肿瘤中有 5 个和 6 个预后不良的肿瘤中有 4 个显示 pERK 阳性细胞质染色（p＞0.9999）。
这些发现表明化疗后而非化疗前的神经母细胞瘤核 pERK 阳性与预后不良相关，可能是 MEK 抑制剂治疗的潜在治疗靶点。
