Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, No. 241 West Huaihai Road, Shanghai, 200030, China.
Burning Rock Biotech, Guangdong Province, Guangzhou, China.
BMC Cancer. 2020 Mar 24;20(1):248. doi: 10.1186/s12885-020-06748-x.
This study was designed to investigate the clinicopathologic features of pulmonary blastomatoid carcinosarcoma and explore the genomic profiles of epithelial and mesenchymal components in this tumor.
Three cases of pulmonary blastomatoid carcinosarcoma were enrolled in this study. Clinicopathologic information and prognostic data were retrospectively reviewed. Diagnostic immunohistochemistry was performed. The epithelial and mesenchymal components were microdissected to investigate the genomic profiles by performing capture-based targeted next generation sequencing.
The epithelial components in patient one consisted of low-grade and high-grade fetal lung adenocarcinoma. Low-grade epithelial cells showed nuclear expression of β-catenin and missense mutation of CTNNB1. The epithelial components in another two patients consisted of high-grade fetal lung adenocarcinoma/enteric adenocarcinoma. The epithelial cells showed membrane staining of β-catenin and harbored no mutation of CTNNB1. The mesenchymal components in all three tumors were composed of primitive round/spindle cells without definite differentiation and showed cytoplasmic dot positive of β-catenin and no corresponding mutation. Within a tumor, both components exhibited relatively comparable molecular profile. In patient one, 4 mutations: RB1, FAT3, PTCH1 and LRP1B were shared by both epithelial and mesenchymal components. Epithelial component had additional mutations in BCOR, CTNNB1, CTCF, FAT1 and DICER1. In patient two, 12 mutations were shared. The epithelial component had BRCA2 mutation and the mesenchymal had mutations in CREBBP, ALK, DNMT3A, ASXL2, MYCN and RICTOR. Patient three had 6 shared mutations. The epithelial component had an additional mutation in KAT6A and the mesenchymal had an additional mutation in APC. Collectively, we observed heterogeneity between epithelial and mesenchymal components of the same tumor.
Blastomatoid carcinosarcoma showed characteristic morphology and immunophenotype. Parallel detection of genetic abnormalities in epithelial and mesenchymal components could provide further evidence for tumor differentiation, molecular targeting and differential diagnosis.
本研究旨在探讨肺胚细胞瘤样癌肉瘤的临床病理特征，并探讨该肿瘤上皮和间充质成分的基因组特征。
本研究纳入了 3 例肺胚细胞瘤样癌肉瘤。回顾性分析了临床病理资料和预后数据。进行了诊断免疫组织化学检测。通过基于捕获的靶向下一代测序对上皮和间充质成分进行微切割，以研究基因组特征。
患者 1 的上皮成分包括低级别和高级别胎儿肺腺癌。低级别上皮细胞表现为β-连环蛋白核表达和 CTNNB1 错义突变。另外 2 例患者的上皮成分均由高级别胎儿肺腺癌/肠型腺癌组成。上皮细胞表现为β-连环蛋白膜染色，且 CTNNB1 无突变。所有 3 例肿瘤的间充质成分均由原始圆形/梭形细胞组成，无明确分化，细胞质点状阳性β-连环蛋白，无相应突变。在一个肿瘤内，两种成分均表现出相对可比的分子特征。在患者 1 中，4 个突变：RB1、FAT3、PTCH1 和 LRP1B 同时存在于上皮和间充质成分中。上皮成分还存在 BCOR、CTNNB1、CTCF、FAT1 和 DICER1 的突变。患者 2 中有 12 个突变共享。上皮成分存在 BRCA2 突变，间充质成分存在 CREBBP、ALK、DNMT3A、ASXL2、MYCN 和 RICTOR 突变。患者 3 有 6 个共享突变。上皮成分存在 KAT6A 突变，间充质成分存在 APC 突变。总的来说，我们观察到同一肿瘤的上皮和间充质成分之间存在异质性。
胚细胞瘤样癌肉瘤具有特征性的形态和免疫表型。在上皮和间充质成分中平行检测遗传异常可为肿瘤分化、分子靶向和鉴别诊断提供进一步证据。
