Immunohistochemical staining of phosphorylated-ERK in post-chemotherapeutic samples is a potential predictor of the prognosis of neuroblastoma
Immunohistochemical staining of phosphorylated-ERK in post-chemotherapeutic samples is a potential predictor of the prognosis of neuroblastoma
复制标题
化疗后样本中磷酸化 ERK 的免疫组织化学染色是神经母细胞瘤预后的潜在预测因子
DOI：
10.1007/s00383-020-04806-w
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发表时间：
2021
影响因子：
1.8
通讯作者：
Tajiri Tatsuro
中科院分区：
文献类型：
--
作者：
Tanaka Tomoko;Togashi Yuichi;Takeuchi Yuki;Higashi Mayumi;Fumino Shigehisa;Tajiri Tatsuro
目的：大多数复发性神经母细胞瘤存在丝裂原活化蛋白激酶(MAPK)通路激活突变。我们先前研究了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。本研究采用磷酸化细胞外信号调节激酶(PERK)免疫组织化学方法，探讨MAPK活性与神经母细胞瘤患者预后的关系，为临床应用MEK抑制剂提供依据。临床结果从病历中进行回顾性收集。结果在化疗前标本中，预后良好和预后差的肿瘤在胞核和胞浆中的PERK状态无明显差异。在化疗后标本中，8例预后良好的肿瘤中有1例PERK阳性，6例预后不良的肿瘤中有4例PERK阳性(p= 0.0909)，8例预后良好的肿瘤中有5例PERK阳性，6例预后不良的肿瘤中有4例PERK阳性(p>； 0.9999)。
PurposeThe 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.MethodsNeuroblastoma 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.ResultsRegarding 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).ConclusionThese 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.