University Hospital of Saint Etienne, North Hospital, Department of Pathology, Saint Etienne, France; University Hospital of Saint Etienne, North Hospital, Plateforme de Biologie Moléculaire des Tumeurs Solides, Saint Etienne, France; Corneal Graft Biology, Engineering, and Imaging Laboratory, BiiGC, EA2521, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France.
University Hospital of Saint Etienne, North Hospital, Department of Pathology, Saint Etienne, France.
Pathology. 2021 Oct;53(6):728-734. doi: 10.1016/j.pathol.2021.01.010. Epub 2021 May 6.
The prognostic impact of tumour grading, cytological and architectural patterns and stromal features in diffuse pleural malignant epithelioid mesothelioma (MEM) has been partly studied but not correlated to molecular features. We performed a retrospective study on 92 MEM in our department in order to assess the prognostic role of architectural and stromal patterns, especially tumour to stroma ratio. Secondly, based on The Cancer Genome Atlas (TCGA) database, we analysed the differentially expressed genes in prognostic groups of interest. Our results showed that tumour grading, tumour to stroma ratio and predominant pattern were related to overall survival, p≤0.001, p=0.01 and p=0.001, respectively. In univariate analysis, for high grade tumours hazard ratio (HR) was 4.75 (2.47-9.16), for stroma poor tumours HR=0.016, for predominant tubular or tubulopapillary pattern HR=0.044. In multivariate analysis, high grade tumours were related to overall survival [HR=3.09 (1.50-6.35), p=0.002] and predominant tubular or tubulopapillary pattern [HR=0.56 (0.32-0.99), p=0.045]. In TCGA analysis, after grading of diagnostic slides, we showed that KRTDAP and CXRCR1 expression was higher in low grade tumours, unlike PDZD7 and GPR176 expression which was higher in high grade tumours. FAM81B had a higher expression in stroma poor tumours. We did not find any differentially expressed genes in the architectural patterns group. Our work suggests that tumour grading is an important parameter in MEM with an underlying genomic basis. The role of tumour to stroma ratio needs to be investigated and might also have a genomic basis.
弥漫性胸膜上皮样恶性间皮瘤（MEM）的肿瘤分级、细胞学和结构模式以及基质特征的预后影响已部分研究，但与分子特征无关。我们在我们的科室对 92 例 MEM 进行了回顾性研究，以评估结构和基质模式的预后作用，特别是肿瘤与基质的比值。其次，基于癌症基因组图谱（TCGA）数据库，我们分析了在感兴趣的预后组中差异表达的基因。我们的结果表明，肿瘤分级、肿瘤与基质的比值和主要模式与总生存率相关，p≤0.001、p=0.01 和 p=0.001。在单因素分析中，高级别肿瘤的危险比（HR）为 4.75（2.47-9.16），基质差的肿瘤 HR=0.016，主要管状或小管乳头状模式 HR=0.044。在多因素分析中，高级别肿瘤与总生存率相关[HR=3.09（1.50-6.35），p=0.002]和主要管状或小管乳头状模式[HR=0.56（0.32-0.99），p=0.045]。在 TCGA 分析中，在对诊断切片进行分级后，我们发现 KRTDAP 和 CXRCR1 的表达在低级别肿瘤中较高，而 PDZD7 和 GPR176 的表达在高级别肿瘤中较高。FAM81B 在基质差的肿瘤中表达较高。我们在结构模式组中没有发现任何差异表达的基因。我们的工作表明，肿瘤分级是 MEM 的一个重要参数，具有潜在的基因组基础。肿瘤与基质的比值的作用需要进一步研究，也可能具有基因组基础。
