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

IF 3.1 2区医学 Q3 IMMUNOLOGY

Infectious Agents and Cancer Pub Date : 2024-01-04 DOI:10.1186/s13027-023-00564-1

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

{"title":"The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases","authors":"Stella Meireles Siqueira, Gabriella Campos-do-Carmo, Paulo Ricardo Garcia da Silva, Isabele Ávila Small, Andreia Cristina De Melo","doi":"10.1186/s13027-023-00564-1","DOIUrl":null,"url":null,"abstract":"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. 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. 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%. 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.","PeriodicalId":13568,"journal":{"name":"Infectious Agents and Cancer","volume":"6 1","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infectious Agents and Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13027-023-00564-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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. 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. 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%. 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.

查看原文本刊更多论文

梅克尔细胞癌病例中 PD-L1 表达和多瘤病毒存在的预后作用

梅克尔细胞癌（MCC）是一种罕见的恶性原发性皮肤肿瘤，呈神经内分泌分化。最近，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）的药物已在晚期梅克尔细胞癌患者中证实了客观和持久的肿瘤消退。本研究旨在描述 MCC 患者的社会人口学、临床和组织病理学特征，同时评估 PD-L1 表达和梅克尔细胞多瘤病毒（MCPyV）的流行情况及其预后作用。这项回顾性研究评估了巴西东南部里约热内卢一家参考癌症中心在1996年至2019年期间诊断出的MCC患者的数据。采用免疫组化方法对肿瘤样本进行了MCPyV和PD-L1检测。采用 Kaplan-Meier 法进行生存期分析，并使用对数秩检验比较曲线。采用多重半参数考克斯模型。P<0.05为显著值。研究共纳入了 65 名患者，诊断时的平均年龄为 72 岁（标准差为 13.9）。56.9%（37/65）的患者为男性，86.2%（56/65）为白人，56.9%（37/64）为文盲或小学未毕业。29例（44.6%）患者的MCPyV免疫组化呈阳性，42例（64.6%）患者的PD-L1阳性率≥1%。MCPyV与PD-L1表达≥1%（p = 0.003）和PD-L1表达≥5%（p = 0.005）之间存在显著关联。在多变量分析中，只有受教育程度和晚期MCC分期表明无进展生存期显著缩短。在总生存期（OS）方面，男性、受教育程度和晚期是风险因素。据估计，I期至III期患者60个月的OS为48.9%，IV期患者为8.9%。这是巴西首次对MCC肿瘤中MCPyV的患病率、PD-L1的表达及其相关性进行评估的大型队列。未发现MCPyV感染或PD-L1表达与生存率之间存在相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY

CiteScore

5.80

自引率

2.70%

发文量

期刊介绍： Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.