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Negative prognostic impact of PD-L1 expression in tumor cells of undifferentiated (anaplastic) carcinoma with osteoclast-like giant cells of the pancreas: study of 13 cases comparing ductal pancreatic carcinoma and review of the literature.
Virchows Archiv ( IF 3.4 ) Pub Date : 2020-05-18 , DOI: 10.1007/s00428-020-02830-8
Jan Hrudka 1 , Kateřina Lawrie 2 , Petr Waldauf 3 , Vanda Ciprová 4 , Jana Moravcová 1, 5 , Radoslav Matěj 1, 4, 6
Affiliation  

Pancreatic carcinoma remains one of the leading cancer-related causes of death worldwide and is generally characterized by a dismal prognosis and limited potential for oncologic treatment. A rare subvariant of pancreatic cancer, undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), has an unpredictable prognosis according to many previous studies, with unexpectedly long survival in individual cases. In this study, we collected, retrospectively, 13 cases of well-documented UCOGCs and performed immunohistochemistry focused on the expression of the programmed death-ligand 1 (PD-L1) and several other potential therapeutic and predictive markers (PanTRK, p53, MSH2, PMS2, and the number of tumor-infiltrating lymphocytes), to explore their correlation with the follow-up of the patients. As a control group, we examined 24 cases of conventional pancreatic ductal adenocarcinoma (PDAC). In our results, PanTRK was negative in all 24 cases. P53 did not show any significant differences between UCOGCs and PDACs, and the entire cohort was MSH2, MLH1, PMS2, and MSH6 positive. Significant differences were present in the analysis of PD-L1: UCOGCs were found to express PD-L1 significantly more frequently and have a higher number of tumor-infiltrating lymphocytes than PDAC. The expression of PD-L1 was related to significantly shorter survival in patients with UCOGC and in the entire cohort. Patients with PD-L1 negative UCOGCs displayed surprisingly long survival in comparison to PD-L1 positive UCOGCs and PDACs (both PD-L1+ and PD-L1-). We compared our results with previously published data, and, after statistical analysis, we were able to identify PD-L1 as an effective prognostic marker of UCOGC and suggest a strong need for a clinical trial of immune checkpoint immunotherapy in patients with advanced PD-L1 positive UCOGC.

中文翻译:

PD-L1 表达对胰腺破骨细胞样巨细胞未分化(间变性)癌肿瘤细胞的负面预后影响:13 例胰腺导管癌比较研究及文献复习。

胰腺癌仍然是世界范围内与癌症相关的主要死亡原因之一,通常具有预后差和肿瘤治疗潜力有限的特点。根据先前的许多研究,胰腺癌的一种罕见亚变体,即具有破骨细胞样巨细胞的未分化癌 (UCOGC),具有不可预测的预后,在个别病例中具有出乎意料的长存活期。在这项研究中,我们回顾性地收集了 13 例有据可查的 UCOGC,并进行了免疫组化,重点关注程序性死亡配体 1 (PD-L1) 和其他几种潜在的治疗和预测标志物(PanTRK、p53、MSH2、 PMS2,以及肿瘤浸润淋巴细胞的数量),以探讨其与患者随访的相关性。作为对照组,我们检查了 24 例常规胰腺导管腺癌 (PDAC)。在我们的结果中,PanTRK 在所有 24 例中均为阴性。P53 在 UCOGCs 和 PDACs 之间没有显示出任何显着差异,并且整个队列都是 MSH2、MLH1、PMS2 和 MSH6 阳性。PD-L1 的分析存在显着差异:与 PDAC 相比,发现 UCOGC 表达 PD-L1 的频率显着更高,并且具有更多数量的肿瘤浸润淋巴细胞。PD-L1 的表达与 UCOGC 患者和整个队列的生存期显着缩短有关。与 PD-L1 阳性 UCOGC 和 PDAC(PD-L1+ 和 PD-L1-)相比,PD-L1 阴性 UCOGC 患者显示出惊人的长生存期。我们将我们的结果与之前发布的数据进行了比较,经过统计分析,
更新日期:2020-05-18
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