Department of Surgical Pathology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Virchows Arch. 2019 Aug;475(2):201-209. doi: 10.1007/s00428-019-02589-7. Epub 2019 May 12.
Papillary proliferation of the endometrium (PPE) is an uncommon lesion that frequently shows mucinous metaplasia. PPE occasionally has concurrent or preceding endometrial hyperplasia and carcinomas, but there is little molecular evidence to support the relationships between PPEs and endometrial neoplasia. In this study, we analyzed the clinicopathological and immunohistochemical features in 30 PPEs (22 simple PPEs and 8 complex papillary hyperplasia (CPH)). Hotspot mutations of KRAS, PI3KCA, AKT1, PTEN (exons 3, 5, and 7), and ARID1A (exons 1 and 14) were detected by pyrosequencing or bidirectional Sanger sequencing. We found that endometrial hyperplasia and carcinoma were more common in CPHs (4/6, 66.7%) than in simple PPEs (4/21, 19.0%) (p < 0.05). Compared with the adjacent normal endometrium, PPEs frequently showed loss of PAX2 (56.7%) and PTEN (10%) expression, diffuse p16 expression (36.7%), decreased PR expression (84.3%), and lower Ki67 labeling index (median 1%, range 1-15%). Simple PPEs and CPHs had similar immunohistochemical features (p > 0.05). KRAS mutations were identified in 14 PPEs and 1 concurrent endometrial carcinoma. The prevalence of KRAS mutations was not statistically different between simple PPEs (10/21, 45.5%) and CPHs (4/8, 50%) (p > 0.05), but was higher in PPEs displaying mucinous metaplasia (12/24, 50%) than in those without (2/6, 33.3%) (p < 0.05). One simple PPE with a KRAS mutation had an AKT1 mutation. No PPEs demonstrated mutations in PI3KCA, PTEN, and ARID1A. In conclusion, both simple PPE and CPH share some common molecular alterations with endometrial neoplasia, in which, KRAS mutations might be a driver.
子宫内膜乳头状增生（PPE）是一种不常见的病变，常伴有黏液样化生。PPE 偶尔与子宫内膜增生和癌并存，但很少有分子证据支持 PPE 与子宫内膜肿瘤之间的关系。在这项研究中，我们分析了 30 例 PPE（22 例单纯 PPE 和 8 例复杂乳头状增生（CPH））的临床病理和免疫组化特征。通过焦磷酸测序或双向 Sanger 测序检测 KRAS、PI3KCA、AKT1、PTEN（外显子 3、5 和 7）和 ARID1A（外显子 1 和 14）的热点突变。我们发现 CPH 中子宫内膜增生和癌更为常见（6/6，66.7%），而单纯 PPE 中则较少见（4/21，19.0%）（p<0.05）。与相邻的正常子宫内膜相比，PPE 常表现出 PAX2（56.7%）和 PTEN（10%）表达缺失、弥漫性 p16 表达（36.7%）、PR 表达减少（84.3%）和 Ki67 标记指数较低（中位数 1%，范围 1-15%）。单纯 PPE 和 CPH 的免疫组化特征相似（p>0.05）。14 例 PPE 和 1 例同时性子宫内膜癌中检测到 KRAS 突变。单纯 PPE（21/10，45.5%）和 CPH（8/4，50%）中 KRAS 突变的发生率无统计学差异（p>0.05），但在有黏液样化生的 PPE（24/12，50%）中高于无黏液样化生的 PPE（6/2，33.3%）（p<0.05）。1 例伴有 KRAS 突变的单纯 PPE 有 AKT1 突变。无 PPE 显示 PI3KCA、PTEN 和 ARID1A 突变。总之，单纯 PPE 和 CPH 与子宫内膜肿瘤具有一些共同的分子改变，其中 KRAS 突变可能是一个驱动因素。
