宫颈小细胞神经内分泌癌（small cell neuroendocrine carcinoma，SCNEC）是一种罕见但高度恶性的肿瘤。虽然高危人乳头瘤病毒（human papillomavirus，HPV）参与许多肿瘤的早期发生阶段，但人们也推测某些其他驱动因子也促进了SCNEC的发展。认识这些致癌因子能够指导肿瘤的靶向治疗。本文报道10例宫颈SCNEC的临床病理特征。利用免疫组织化学方法分析pl6、p53、突触素和嗜铬粒蛋白的表达状况；原位杂交和聚合酶链反应技术评估高危HPV和/或HPV18，以及基于637个组合基因的二代测序技术来检测突变的基因。患者年龄从28岁到68岁不等（平均，45.6岁；中位数，40.5岁）。结果发现，所有肿瘤组织均有pl6和突触素的弥漫性表达。除1例外，嗜铬粒蛋白在其他肿瘤组织内都呈阳性（从局灶性到弥漫性不等）。在6例肿瘤组织中检测到HPV18，而只有1例发现有HPV35阳性。在8例肿瘤组织发现至少1例有驱动因子突变，4例患者检测到有TP53体细胞突变，其中3例伴有异常的p53免疫染色；在3例肿瘤中检测到4个P1K3CA突变（p.G106A、p.N345T、p.E545K和p.E545D），其中2例也伴有TP53基因突变；在4例肿瘤组织内检测到涉及KRAS、Erbb2、c-Myc，NOTCH1、SCL6或NCOA3的肿瘤驱动基因突变，它们也通常伴有抑制因子PTEN、RB1、BRCA1、BRCA2和AR1D1B的突变，从而共同引起肿瘤性病变。靶向二代测序技术检测发现SCNEC的MAPK、PI3K/AKT/mTOR和TP53/BRCA 遗传信号传导途径发生变化。这为SCNEC这种高度恶性肿瘤的个体化靶向治疗提供了可行性。
AmJSurg Pathol 2018；42：750.760
美国外科病理学杂志中文版2019年第一期摘要NO.5
沈士亮翻译/审校
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