Central Animal Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Sci Rep. 2023 May 25;13(1):8511. doi: 10.1038/s41598-023-35703-6.
Patient-derived xenograft (PDX) tumor models are known to maintain the genomic and phenotypic profiles, including the histopathological structures, of the parental tumors. On the other hand, unique enrichment of single-nucleotide variants or copy number aberrations has been reported in several types of tumors. However, an understanding of endometrial carcinoma PDXs is limited. The purpose of the present study was to clarify the presence or absence of the molecular properties of endometrial carcinomas in PDXs passaged up to eight times. Established PDXs of endometrioid carcinomas maintained their histopathological characteristics, but those of carcinosarcomas predominantly consisted of sarcomatous components when compared to the parental tumors. Alterations in the proportion of cells with positive/negative immunohistochemical staining for estrogen receptor, PTEN, PAX8, and PAX2 were observed, whereas the proportions of cells with AE1/AE3, TP53, ARID1A, PMS2, and MSH6 staining were unchanged. Variants of cancer-associated genes were compared between PDXs and parental tumors. Mutations in POLE and a frameshift deletion in BRCA1 were observed in the parental tumor tissue in each of the six cases, and additional genomic alterations, which were not apparently related to histopathological and immunohistochemical alterations, were found in the PDXs of these cases. The genomic and phenotypic alterations observed between endometrial carcinoma PDXs and parental tumors were partly associated with endometrial cancer-specific characteristics related to cellular differentiation and gene mutations.
患者来源异种移植（PDX）肿瘤模型被认为保持了亲本肿瘤的基因组和表型特征，包括组织病理学结构。另一方面，已经在几种类型的肿瘤中报道了单核苷酸变异或拷贝数异常的独特富集。然而，对子宫内膜癌 PDX 的了解有限。本研究的目的是阐明 PDX 传代至 8 次时是否存在子宫内膜癌的分子特性。建立的子宫内膜样癌 PDX 保持了其组织病理学特征，但与亲本肿瘤相比，癌肉瘤的 PDX 主要由肉瘤成分组成。观察到雌激素受体、PTEN、PAX8 和 PAX2 的免疫组织化学染色阳性/阴性细胞比例的改变，而 AE1/AE3、TP53、ARID1A、PMS2 和 MSH6 染色的细胞比例不变。比较了 PDX 与亲本肿瘤之间癌症相关基因的变异。在这 6 个病例中的每个病例的亲本肿瘤组织中都观察到 POLE 的突变和 BRCA1 的框移缺失，并且在这些病例的 PDX 中还发现了其他与组织病理学和免疫组织化学改变无关的基因组改变。在子宫内膜癌 PDX 与亲本肿瘤之间观察到的基因组和表型改变部分与与细胞分化和基因突变相关的子宫内膜癌特异性特征有关。
