Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University (LMU), Munich, Germany.
PLoS One. 2018 Feb 16;13(2):e0192881. doi: 10.1371/journal.pone.0192881. eCollection 2018.
The objective of this study was to evaluate the prognostic value of ARID1A, p53, p21, p16 and ß-Catenin in endometrioid and clear cell ovarian and endometrial carcinomas.
97 tumors were available for analysis of ARID1A, p53, p21, p16 and ß-Catenin with the techniques of tissue microarray and immunohistochemistry. 32 were ovarian carcinomas and 65 were endometrial carcinomas.
Endometrioid ovarian carcinomas showed negative staining for ARID1A (a) and p21 (b), aberrant expression of p53 (c) and p16 (d) and ß-Catenin positive nuclear expression (e) respectively in 19% (a), 100% (b), 28.6% (c), 52.4% (d) and 4.8% (e) of all cases. In the group of clear cell ovarian carcinomas it was 63.6% (a), 100% (b), 81.8% (c), 54.5% (d) and 0% (e). For endometrioid uterine carcinomas it was 75.7% (a), 94.9% (b), 30.5% (c), 52.1% (d) and 6.8% (e) and for clear cell uterine carcinomas it was 8.6% (a), 100% (b), 50% (c), 100% (d) and 0% (e). Survival analysis showed that negative expression of ARID1A, p53 aberrant expression and ß-Catenin nuclear positive staining are independent negative prognosticators in both, clear cell and endometrioid carcinoma, regardless of ovarian or uterine origin. Cox-Regression analysis showed them again as negative prognostic factors. Furthermore, we found a significant correlation between ARID1A and ß-Catenin expression in endometrioid uterine tumors.
The analyzed gynaecological carcinoma showed a distinct expression scheme of proteins that are associated with tumor suppression. We may conclude that ARID1A, p53 and ß-Catenin are the strongest prognostic factors by analyzing a subgroup of tumor suppressor genes in clear cell and endometrioid subtypes of ovarian and endometrial cancer and may be used along with traditional morphological and clinical characteristics for prognosis.
本研究旨在评估 ARID1A、p53、p21、p16 和 β-连环蛋白在子宫内膜样和透明细胞卵巢和子宫内膜癌中的预后价值。
使用组织微阵列和免疫组织化学技术分析了 97 例 ARID1A、p53、p21、p16 和 β-连环蛋白的肿瘤。其中 32 例为卵巢癌,65 例为子宫内膜癌。
子宫内膜样卵巢癌分别有 19%(a)、100%(b)、28.6%(c)、52.4%(d)和 4.8%(e)的病例表现为 ARID1A(a)和 p21(b)阴性染色、p53(c)和 p16(d)异常表达以及β-连环蛋白阳性核表达(e),而在透明细胞卵巢癌组中,这一比例分别为 63.6%(a)、100%(b)、81.8%(c)、54.5%(d)和 0%(e)。子宫内膜样子宫癌分别有 75.7%(a)、94.9%(b)、30.5%(c)、52.1%(d)和 6.8%(e)的病例有 ARID1A 表达缺失,而透明细胞子宫癌中这一比例分别为 8.6%(a)、100%(b)、50%(c)、100%(d)和 0%(e)。生存分析显示,ARID1A 阴性表达、p53 异常表达和β-连环蛋白阳性核染色是透明细胞癌和子宫内膜样癌中独立的预后不良因素,无论其起源于卵巢还是子宫。Cox 回归分析再次表明它们是预后不良的因素。此外,我们还发现子宫内膜样子宫肿瘤中 ARID1A 与β-连环蛋白表达之间存在显著相关性。
本研究分析的妇科癌显示出与肿瘤抑制相关的独特蛋白表达谱。我们可以得出结论,通过分析透明细胞和子宫内膜样卵巢和子宫内膜癌亚组中的一组肿瘤抑制基因,ARID1A、p53 和β-连环蛋白是最强的预后因素,并可与传统的形态学和临床特征一起用于预后。