Takayanagi Daisuke, Hirose Sou, Kuno Ikumi, Asami Yuka, Murakami Naoya, Matsuda Maiko, Shimada Yoko, Sunami Kuniko, Komatsu Masaaki, Hamamoto Ryuji, Kato Mayumi Kobayashi, Matsumoto Koji, Kohno Takashi, Kato Tomoyasu, Shiraishi Kouya, Yoshida Hiroshi
Division of Genome Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-19-18, Nishishinbashi, Minato-ku, Tokyo 105-8471, Japan.
Cancers (Basel). 2021 Mar 10;13(6):1215. doi: 10.3390/cancers13061215.
Neuroendocrine carcinoma of the cervix (NECC) is a rare and highly aggressive tumor with no efficient treatment. We examined genetic features of NECC and identified potential therapeutic targets. A total of 272 patients with cervical cancer (25 NECC, 180 squamous cell carcinoma, 53 adenocarcinoma, and 14 adenosquamous carcinoma) were enrolled. Somatic hotspot mutations in 50 cancer-related genes were detected using the Ion AmpliSeq Cancer Hotspot Panel v2. Human papillomavirus (HPV)-positivity was examined by polymerase chain reaction (PCR)-based testing and in situ hybridization assays. Programmed cell death-ligand 1 (PD-L1) expression was examined using immunohistochemistry. Somatic mutation data for 320 cases of cervical cancer from the Project GENIE database were also analyzed. NECC showed similar (, 32%; , 24%) and distinct (, 20%; , 16%; , 12%; , 12%) alterations compared with other histological types. The GENIE cohort had similar profiles and mutations in 27.6% of NECC cases. Eleven (44%) cases had at least one actionable mutation linked to molecular targeted therapies and 14 (56%) cases showed more than one combined positive score for PD-L1 expression. HPV-positivity was observed in all NECC cases with a predominance of HPV-18. We report specific gene mutation profiles for NECC, which can provide a basis for the development of novel therapeutic strategies.
宫颈神经内分泌癌（NECC）是一种罕见且侵袭性很强的肿瘤，目前尚无有效的治疗方法。我们研究了NECC的基因特征并确定了潜在的治疗靶点。共纳入了272例宫颈癌患者（25例NECC、180例鳞状细胞癌、53例腺癌和14例腺鳞癌）。使用Ion AmpliSeq癌症热点Panel v2检测50个癌症相关基因中的体细胞热点突变。通过基于聚合酶链反应（PCR）的检测和原位杂交分析来检测人乳头瘤病毒（HPV）阳性情况。使用免疫组织化学检测程序性细胞死亡配体1（PD-L1）的表达。还分析了来自GENIE数据库的320例宫颈癌的体细胞突变数据。与其他组织学类型相比，NECC显示出相似（，32%；，24%）和不同（，20%；，16%；，12%；，12%）的改变。GENIE队列具有相似的特征，27.6%的NECC病例存在突变。11例（44%）病例至少有一个与分子靶向治疗相关的可操作突变，14例（56%）病例的PD-L1表达显示多个联合阳性评分。在所有NECC病例中均观察到HPV阳性，以HPV-18为主。我们报告了NECC的特定基因突变谱，可为开发新的治疗策略提供依据。
