Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
Sci Rep. 2023 Mar 3;13(1):3587. doi: 10.1038/s41598-023-30624-w.
Anal squamous cell carcinoma (ASCC) is a rare tumor of the gastrointestinal tract. We aimed to compare the genetic backgrounds and their effect on clinical outcomes between Japanese and Caucasian patients with ASCC. Forty-one patients diagnosed with ASCC at the National Cancer Center Hospital were enrolled and evaluated for clinicopathological features, human papillomavirus (HPV) infection, HPV genotypes, p16 expression, PD-L1, and association of p16 status with the efficacy of concurrent chemoradiotherapy (CCRT). Target sequencing for hotspot mutations in 50 cancer-related genes was performed using genomic DNA from 30 available samples. Of 41 patients, 34 were HPV-positive (among them, HPV 16 was predominant; 73.2%); 38 patients were p16-positive (92.7%); and 39 patients received CCRT, of whom 36 were p16-positive and three p16-negative. p16-positive patients showed better complete response than p16-negative patients. Among 28 samples, 15 showed mutations in PIK3CA, FBXW7, ABL1, TP53, and PTEN; no difference in mutation profiles between the Japanese and Caucasian cohorts was observed. Actionable mutations were detected in both Japanese and Caucasian patients with ASCC. Genetic backgrounds, such as the HPV 16 genotype and PIK3CA mutations, were common regardless of ethnicity. p16 status may be a prognostic biomarker for CCRT in Japanese patients with ASCC.
肛门鳞状细胞癌 (ASCC) 是一种罕见的胃肠道肿瘤。我们旨在比较日本和高加索人群 ASCC 患者的遗传背景及其对临床结局的影响。在国家癌症中心医院，我们纳入并评估了 41 例 ASCC 患者的临床病理特征、人乳头瘤病毒 (HPV) 感染、HPV 基因型、p16 表达、PD-L1，并分析了 p16 状态与同期放化疗 (CCRT) 疗效的关系。使用 30 例可获得的样本的基因组 DNA 对 50 个与癌症相关基因的热点突变进行了靶向测序。在 41 例患者中，34 例为 HPV 阳性 (其中 HPV16 占优势；73.2%)；38 例为 p16 阳性 (92.7%)；39 例接受了 CCRT，其中 36 例为 p16 阳性，3 例为 p16 阴性。p16 阳性患者的完全缓解率优于 p16 阴性患者。在 28 个样本中，有 15 个样本检测到 PIK3CA、FBXW7、ABL1、TP53 和 PTEN 突变；日本和高加索队列之间的突变谱没有差异。在日本和高加索 ASCC 患者中均检测到了可操作的突变。无论种族如何，HPV16 基因型和 PIK3CA 突变等遗传背景都很常见。p16 状态可能是日本 ASCC 患者 CCRT 的预后生物标志物。
