Department of Immunotechnology, Lund University, Lund, Sweden.
Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
Br J Haematol. 2020 Dec;191(5):796-805. doi: 10.1111/bjh.17023. Epub 2020 Aug 4.
Survival for patients diagnosed with mantle cell lymphoma (MCL) has improved drastically in recent years. However, patients carrying mutations in tumour protein p53 (TP53) do not benefit from modern chemotherapy-based treatments and have poor prognosis. Thus, there is a clinical need to identify missense mutations through routine analysis to enable patient stratification. Sequencing is not widely implemented in clinical practice for MCL, and immunohistochemistry (IHC) is a feasible alternative to identify high-risk patients. The aim of the present study was to investigate the accuracy of p53 as a tool to identify patients with TP53 missense mutations and the prognostic impact of overexpression and mutations in a Swedish population-based cohort. In total, 317 cases were investigated using IHC and 255 cases were sequenced, enabling analysis of p53 and TP53 status among 137 cases divided over the two-cohort investigated. The accuracy of predicting missense mutations from protein expression was 82%, with sensitivity at 82% and specificity at 100% in paired samples. We further show the impact of p53 expression and TP53 mutations on survival (hazard ratio of 3·1 in univariate analysis for both), and the association to risk factors, such as high MCL International Prognostic Index, blastoid morphology and proliferation, in a population-based setting.
近年来，被诊断为套细胞淋巴瘤 (MCL) 的患者的生存率有了显著提高。然而，携带肿瘤蛋白 p53 (TP53) 突变的患者不能从现代基于化疗的治疗中获益，且预后较差。因此，临床上需要通过常规分析识别错义突变，以便对患者进行分层。测序在 MCL 的临床实践中并未广泛实施，免疫组织化学 (IHC) 是识别高危患者的可行替代方法。本研究旨在调查 p53 作为一种工具来识别具有 TP53 错义突变的患者的准确性，以及在瑞典基于人群的队列中 p53 过表达和突变的预后影响。总共使用 IHC 检测了 317 例病例，并用测序检测了 255 例病例，使在两个队列中分别调查的 137 例病例能够进行 p53 和 TP53 状态分析。从蛋白表达预测错义突变的准确性为 82%，在配对样本中，敏感性为 82%，特异性为 100%。我们进一步显示了 p53 表达和 TP53 突变对生存的影响（单因素分析中的危险比分别为 3.1），并在基于人群的环境中，与高 MCL 国际预后指数、母细胞样形态和增殖等危险因素相关联。
