Taboada Rodrigo, Claro Laura, Felismino Tiago, de Jesus Victor Hugo, Barros Milton, Riechelmann Rachel P
Department of Medical Oncology, A.C.Camargo Cancer Center, São Paulo, Brazil.
Department of Pathology, A.C.Camargo Cancer Center, São Paulo, Brazil.
J Neuroendocrinol. 2022 Apr;34(4):e13099. doi: 10.1111/jne.13099. Epub 2022 Feb 16.
The 2019 Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3 NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3 NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3 NET, with a 23% change in diagnosis. Median overal survival for G3 NET and NEC patients was 55.6 and 11.9 months, respectively (hazard ratio = 2.78 [95% confidence interval = 1.09-7.11], p = .042), which was confirmed by an adjusted analysis (hazard ratio = 2.90 NEC vs. G3 NET; p = .03). NGS was performed in 32 cases: 21 NEC and 11 G3 NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3 NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors.
2019年，世界卫生组织（WHO）根据形态学和增殖情况将3级（G3）胃肠胰（GEP）神经内分泌肿瘤（NEN）重新分类为神经内分泌癌（NEC）或肿瘤（G3 NET）。然而，关于G3 NEN分子特征的数据很少。我们比较了这两组的临床病理和分子特征。我们回顾性分析了连续的G3 GEP NEN患者，对其肿瘤组织进行复查，根据WHO 2019年标准重新分类，并通过二代测序（NGS）进行分析。2000年至2019年期间，43例患者进行了病理复查：29例（67%）为NEC，14例（33%）为G3 NET，诊断改变率为23%。G3 NET和NEC患者的中位总生存期分别为55.6个月和11.9个月（风险比=2.78 [95%置信区间=1.09 - 7.11]，p = 0.042），经校正分析得到证实（风险比=NEC与G3 NET相比为2.90；p = 0.03）。对32例病例进行了NGS检测：21例NEC和11例G3 NET。RB1和PTEN突变仅在NEC中出现。NEC的中位肿瘤突变负荷为每兆碱基5（0 - 67）个突变，G3 NET为4.5（0 - 9）个。3例（14.3%）NEC病例存在微卫星不稳定性。总之，病理复查对于评估预后和制定治疗方案至关重要。G3 GEP NEN通常肿瘤突变负荷较低且可操作的突变较少，但14%的NEC病例微卫星不稳定，可能从免疫检查点抑制剂中获益。
