Institute of Pathology and Neuropathology, University of Tuebingen, Liebermeisterstraße 8, 72076, Tuebingen, Germany.
Institute of Pathology, Ludwigs-Maximilians University of Munich, Thalkirchner Straße 36, 80337, Munich, Germany.
Virchows Arch. 2019 Oct;475(4):479-488. doi: 10.1007/s00428-019-02647-0. Epub 2019 Aug 27.
Recent studies have shown that re-expression of stem cell factors contribute to pathogenesis, therapy resistance, and recurrent disease in ovarian carcinomas. In this study, we compare the expression and co-expression of stem cell markers ALDH1 and SOX2 in different types of serous ovarian tumors. A total of 215 serous ovarian tumors (161 high-grade serous carcinomas (HGSC), 17 low-grade serous carcinomas (LGSC), 37 atypical proliferative serous tumors (APST)), and 10 cases of serous tubal intraepithelial carcinoma (STIC) were analyzed. Double immunostaining experiments addressed the association of cell proliferation (Ki67) with ALDH1 and the potential co-expression of SOX2 and ALDH1. The prognostic effect was analyzed in the cohort of HGSC. Expression of ALDH1and/or SOX2 was detected with increased frequency in HGSC (88.8%), compared with LGSC (70.5%) and APST (36.4%), while ALDH1 alone was significantly more frequently expressed in LGSC. The majority of all tumor types showed expression of ALDH1 and SOX2 in different cells. Only a minority of HGSC (4.6%) and STIC (20%) showed SOX2/ALDH1 co-expression in > 10% of tumor cells. Double staining also revealed that ALDH1 is associated with the non-proliferating Ki67-negative fraction consistent with a stem cell phenotype. Co-expression of ALDH1 and SOX2 or ALDH1 and Ki67 has no effect on survival. Expression of stem cell factors ALDH1 and/or SOX2 shows increased frequency in high-grade serous ovarian carcinomas compared to low-grade carcinomas and borderline tumors, supporting the concept that stem cell markers play different biological roles in low-grade versus high-grade serous neoplasia of the ovary.
最近的研究表明，干细胞因子的重新表达有助于卵巢癌的发病机制、治疗抵抗和疾病复发。在这项研究中，我们比较了不同类型浆液性卵巢肿瘤中干细胞标志物 ALDH1 和 SOX2 的表达和共表达。共分析了 215 例浆液性卵巢肿瘤（161 例高级别浆液性癌（HGSC）、17 例低级别浆液性癌（LGSC）、37 例非典型增生性浆液性肿瘤（APST））和 10 例浆液性输卵管上皮内癌（STIC）。双免疫染色实验研究了细胞增殖（Ki67）与 ALDH1 的关联以及 SOX2 和 ALDH1 的潜在共表达。在 HGSC 队列中分析了预后效应。与 LGSC（70.5%）和 APST（36.4%）相比，HGSC 中 ALDH1 和/或 SOX2 的表达频率增加（88.8%），而 LGSC 中 ALDH1 单独表达更为频繁。所有肿瘤类型的大多数均显示出 ALDH1 和 SOX2 在不同细胞中的表达。只有少数 HGSC（4.6%）和 STIC（20%）在>10%的肿瘤细胞中显示 SOX2/ALDH1 共表达。双染色还表明，ALDH1 与非增殖 Ki67 阴性部分相关，与干细胞表型一致。ALDH1 和 SOX2 或 ALDH1 和 Ki67 的共表达对生存没有影响。与低级别癌和交界性肿瘤相比，高级别浆液性卵巢癌中干细胞因子 ALDH1 和/或 SOX2 的表达频率增加，支持干细胞标志物在卵巢低级别和高级别浆液性肿瘤中发挥不同生物学作用的概念。
