Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) and Institut du Cancer de Montréal, Montreal, Canada.
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada.
J Pathol Clin Res. 2019 Jul;5(3):177-188. doi: 10.1002/cjp2.131. Epub 2019 Apr 20.
The aim of this study was to describe the expression of special AT-rich sequence-binding protein 2 (SATB2) in ovarian endometrioid carcinoma (EC). SATB2 is a nuclear matrix-associated transcription factor that is associated with abnormal expression in certain cancers but has not been reported for ovarian carcinoma. SATB2 mRNA and protein expression was first assessed in a pilot cohort of 26 samples by Affymetrix microarray and by routine immunohistochemistry on a small tissue microarray. A large multicenter validation cohort representing the well-characterized cases of 235 ovarian EC from the Canadian Ovarian Experimental Unified Resource (COEUR) was then used to validate this result and to assess the prognostic impact of SATB2 expression. SATB2 staining was scored as negative, weak, moderate, and strong intensity, and by percentage of stained cells. No SATB2 expression was observed in clear cell carcinomas but 10% (n = 3) of the ECs in the pilot cohort showed SATB2 expression. In the validation cohort, strong expression was observed in 11% of ECs, while weak or moderate expression levels were detected in 12% of cases. Evaluation of SATB2 expression with clinicopathological parameters revealed an association with patient age and Federation International of Gynecology and Obstetrics grade but not with disease stage or postoperative residual disease. Any expression of SATB2, independent of intensity, was also associated with longer survival and improved progression-free survival with hazard ratio (HR) = 0.14 (95% CI 0.03-0.56) and HR = 0.16 (95% CI 0.02-1.24) respectively. A greater beneficial effect was observed in patients with stage III/IV disease compared to patients with stage I/II disease. Furthermore, direct comparison of SATB2 with other reported prognostic biomarkers such as progesterone receptor, CDX2 and β-catenin within this cohort showed that SATB2 had the strongest association with survival. Given the current lack of accurate prognostic factors for these patients, SATB2 has promising clinical utility and warrants further study.
本研究旨在描述特殊富含 AT 序列结合蛋白 2(SATB2)在卵巢子宫内膜样癌(EC)中的表达。SATB2 是一种核基质相关转录因子,与某些癌症中的异常表达有关,但尚未报道用于卵巢癌。首先通过 Affymetrix 微阵列和小型组织微阵列的常规免疫组织化学,在 26 例样本的试点队列中评估了 SATB2 mRNA 和蛋白表达。然后,使用代表来自加拿大卵巢实验统一资源(COEUR)的 235 例卵巢 EC 充分特征病例的大型多中心验证队列来验证该结果,并评估 SATB2 表达的预后影响。SATB2 染色被评为阴性、弱阳性、中度和强阳性,并根据染色细胞的百分比进行评分。在透明细胞癌中未观察到 SATB2 表达,但在试点队列中 10%(n=3)的 EC 显示 SATB2 表达。在验证队列中,11%的 EC 中观察到强表达,而 12%的病例中检测到弱阳性或中度表达水平。评估 SATB2 表达与临床病理参数的关系显示与患者年龄和国际妇产科联合会(FIGO)分级相关,但与疾病分期或术后残留疾病无关。任何 SATB2 表达(独立于强度)也与更长的生存时间和更好的无进展生存期相关,风险比(HR)分别为 0.14(95%CI 0.03-0.56)和 0.16(95%CI 0.02-1.24)。在 III/IV 期疾病患者中观察到更大的有益效果,而在 I/II 期疾病患者中则不然。此外,在该队列中,与其他报道的预后生物标志物(如孕激素受体、CDX2 和β-连环蛋白)直接比较表明,SATB2 与生存的相关性最强。鉴于目前这些患者缺乏准确的预后因素,SATB2 具有有希望的临床应用价值,值得进一步研究。