Gleeson Ferga C, Levy Michael J, Roden Anja C, Boardman Lisa A, Sinicrope Frank A, McWilliams Robert R, Zhang Lizhi
Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota, United States.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States.
Endosc Int Open. 2018 Oct;6(10):E1278-E1282. doi: 10.1055/a-0650-4447. Epub 2018 Oct 8.
The US FDA recently approved a cancer treatment with pembrolizumab based upon the tumor biomarker status of deficient mismatch repair (dMMR) rather than a specific disease-based approach. We sought to determine if endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) could determine dMMR and quantification of PD-L1 expression to potentially guide the delivery of tumor agnostic immunotherapy. Immunohistochemistry was performed on archived pancreas core biopsy specimens. Tumors with absent nuclear staining of DNA mismatch repair proteins represented dMMR. Tumors were considered to have any or high PD-L1 expression, if expressed in ≥ 1 % or ≥ 50 % of tumor cells. Histologic specimen adequacy for MMR status assessment was satisfactory in 97.2 % of tumors. dMMR and high PD-L1 expression was identified in 3 % and 8.1 % of the cohort. In the setting of tumor type agnostic immunotherapy, it is projected that at least 3 % of malignant pancreas lesions will be sensitive to pembrolizumab and up to 8 % sensitive to the family of immune checkpoint inhibitors. This highlights the expanding role of EUS-FNB in the field of precision immuno-oncology.
美国食品药品监督管理局（US FDA）最近基于错配修复缺陷（dMMR）的肿瘤生物标志物状态而非基于特定疾病的方法，批准了一种使用帕博利珠单抗的癌症治疗方法。我们试图确定内镜超声引导下细针穿刺活检（EUS-FNB）是否能够确定dMMR以及PD-L1表达的定量，以潜在地指导不考虑肿瘤类型的免疫治疗。对存档的胰腺核心活检标本进行免疫组织化学检查。DNA错配修复蛋白细胞核染色缺失的肿瘤代表dMMR。如果肿瘤细胞中≥1%或≥50%表达，则认为肿瘤有任何或高PD-L1表达。97.2%的肿瘤组织学标本对于MMR状态评估是足够的。在该队列中，dMMR和高PD-L1表达分别在3%和8.1%的病例中被发现。在不考虑肿瘤类型的免疫治疗背景下，预计至少3%的恶性胰腺病变对帕博利珠单抗敏感，高达8%对免疫检查点抑制剂家族敏感。这突出了EUS-FNB在精准免疫肿瘤学领域不断扩大的作用。
