默克尔细胞癌病例中PD-L1表达及多瘤病毒的存在与预后的关系。

The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases.

作者信息

Siqueira Stella Meireles, Campos-do-Carmo Gabriella, da Silva Paulo Ricardo Garcia, Small Isabele Ávila, De Melo Andreia Cristina

机构信息

Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

Dermatology, Gávea Medical Center, Rio de Janeiro, Brazil.

出版信息

Infect Agent Cancer. 2024 Jan 4;19(1):1. doi: 10.1186/s13027-023-00564-1.

DOI:10.1186/s13027-023-00564-1

PMID:38178185

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10768145/

Abstract

BACKGROUND

Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles.

METHODS

Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan-Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant.

RESULTS

A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%.

CONCLUSIONS

This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.

摘要

背景

默克尔细胞癌（MCC）是一种罕见的原发性皮肤恶性肿瘤，具有神经内分泌分化特征。近来，阻断程序性细胞死亡蛋白1和程序性细胞死亡蛋白配体1通路（PD-1/PD-L1）的药物已在晚期MCC患者中显示出客观且持久的肿瘤消退效果。本研究旨在描述MCC患者的社会人口统计学、临床和组织病理学特征，同时评估PD-L1表达和默克尔细胞多瘤病毒（MCPyV）的患病率及其预后作用。

方法

在一项回顾性研究中，对1996年至2019年间在巴西东南部里约热内卢一家参考癌症中心诊断为MCC的患者数据进行了评估。采用免疫组织化学方法对肿瘤样本进行MCPyV和PD-L1检测。采用Kaplan-Meier方法进行生存分析，并使用对数秩检验比较曲线。使用多元半参数Cox模型。p值<0.05被认为具有统计学意义。

结果

本研究共纳入65例患者，诊断时的平均年龄为72岁（标准差13.9）。患者中56.9%（37/65）为男性，86.2%（56/65）为白人，56.9%（37/64）为文盲或小学未毕业。MCPyV免疫组织化学检测阳性29例（44.6%），PD-L1阳性率≥1%的有42例（64.6%）。MCPyV与PD-L1表达≥1%（p=0.003）和PD-L1表达≥5%（p=0.005）之间存在显著相关性。在多变量分析中，只有教育水平和晚期MCC分期显示出无进展生存期在统计学上显著较差。关于总生存期（OS），男性、教育水平和晚期是危险因素。I至III期60个月时的估计总生存率为48.9%，IV期为8.9%。