Yuce Tuna Han, Ak Guntulu, Metintas Selma, Dundar Emine, Roe Oluf Dimitri, Panou Vasiliki, Metintas Muzaffer
Department of Chest Diseases, Eskisehir Osmangazi University Medical Faculty, Eskisehir, Turkey.
Lung and Pleural Cancers Research and Clinical Center, Eskisehir Osmangazi University, Eskisehir, Turkey.
J Cancer Res Clin Oncol. 2024 Jan 27;150(2):38. doi: 10.1007/s00432-023-05565-6.
There are currently no methods to predict response to chemotherapy in pleural mesothelioma (PM). The aim of this study is to investigate the predictive and prognostic role of BAP1, WT1 and calretinin expression and their combinations in pre-treatment tumor samples by immunohistochemical (IHC) staining.
The study included consecutive PM patients treated with chemotherapy alone at a University hospital between 2009 and 2020. BAP1 analyses were performed on formalin-fixed, paraffin-embedded tumor tissue samples of the patients, while WT1 and calretinin information were obtained from the histopathological diagnosis records.
Of the total 107 patients included, 64% had loss of BAP1 expression, whereas 77% had WT1 and 86% had calretinin expression. Patients with the presence of BAP1 expression, one or both of the other two markers, or loss of expression of all three markers (unfavorable status) were more likely to not respond to chemotherapy than those with the presence of all three markers or loss of BAP1 expression and expression of one or two other markers (favorable status) (p = 0.001). Median survival time of patients with favorable and unfavorable status was 15 ± 1.7 and 8.0 ± 2.4 months, respectively (p = 0.027). After adjustment for histopathology and stage, loss of BAP1 (HR = 0.54, 95%CI 0.35-0.83), WT1 (1.75, 1.06-2.90), calretinin (2.09, 1.14-3.84) expression and favourable panel (0.50, 0.27-0.92) was associated with prognosis.
The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.
目前尚无预测胸膜间皮瘤（PM）化疗反应的方法。本研究旨在通过免疫组织化学（IHC）染色研究BAP1、WT1和钙视网膜蛋白表达及其组合在治疗前肿瘤样本中的预测和预后作用。
该研究纳入了2009年至2020年期间在一家大学医院接受单纯化疗的连续性PM患者。对患者福尔马林固定、石蜡包埋的肿瘤组织样本进行BAP1分析，而WT1和钙视网膜蛋白信息则从组织病理学诊断记录中获取。
在纳入的107例患者中，64%的患者BAP1表达缺失，而77%的患者有WT1表达，86%的患者有钙视网膜蛋白表达。与具有所有三种标志物或BAP1表达缺失及一种或两种其他标志物表达（有利状态）的患者相比，具有BAP1表达、其他两种标志物中的一种或两种或所有三种标志物表达缺失（不利状态）的患者对化疗无反应的可能性更高（p = 0.001）。有利和不利状态患者的中位生存时间分别为15±1.7个月和8.0±2.4个月（p = 0.027）。在对组织病理学和分期进行调整后，BAP1表达缺失（HR = 0.54，95%CI 0.35 - 0.83）、WT1（1.75，1.06 - 2.90）、钙视网膜蛋白（2.09，1.14 - 3.84）表达及有利组合（0.50，0.27 - 0.92）与预后相关。
用于PM常规诊断的IHC生物标志物BAP1、WT1和钙视网膜蛋白及其组合，是首批与化疗反应相关的生物标志物，可能是为PM患者选择一线铂类培美曲塞治疗患者的有用工具。正在进行大型队列研究的验证。
