免疫组织化学标志物的监督聚类，以区分非典型子宫内膜增生与 1 级子宫内膜癌。

Supervised clustering of immunohistochemical markers to distinguish atypical endometrial hyperplasia from grade 1 endometrial cancer.

机构信息

Service de Gynécologie-Obstétrique, Hôpital Tenon, AP-HP, 4 rue de la Chine, 75020 Paris, France; Institut Universitaire de Cancérologie, Université Pierre et Marie Curie, Paris 6, France.

Service de Gynécologie-Obstétrique, Hôpital Tenon, AP-HP, 4 rue de la Chine, 75020 Paris, France; Institut Universitaire de Cancérologie, Université Pierre et Marie Curie, Paris 6, France; ER2 UPMC, Université Pierre et Marie Curie, Paris 6, France.

出版信息

Gynecol Oncol. 2014 May;133(2):205-10. doi: 10.1016/j.ygyno.2014.02.018. Epub 2014 Feb 17.

DOI:10.1016/j.ygyno.2014.02.018

PMID:24556060

Abstract

OBJECTIVES

Differentiation between grade-1 endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) is crucial to determine optimal surgical management. However, discrepancies exist between preoperative diagnosis of AEH and final histology. Our aim was to establish clusters of immunohistochemical markers to distinguish AEH from grade-1 EC.

METHODS

We studied 13 immunohistochemical markers (steroid receptors, pro/anti apoptotic proteins, metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP), and CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating grade-1 EC from AEH.

RESULTS

From 42 tissue samples (20 ECs and 22 AEHs), we found 3 clusters of co-expressed proteins: Cluster 1 included 3 proteins (over-expression of MMP-9 and under-expression of estrogen receptor (ER) and progesterone receptor (PR) A in grade-1 EC compared to AEH); cluster 2 showed an MMP-9 over-expression and ER under-expression; cluster 3 showed over-expression of MMP-9 and bcl-2 and under-expression of ER, PR A and CD44-v6 variant. These three clusters together predicted grade-1 EC with a misclassification rate of 8%.

CONCLUSION

Supervised clustering of immunohistochemical markers in grade-1 EC and AEH tissue identified proteins acting together and resulted in accurate differentiation between these two histological entities.

摘要

目的

区分 1 级子宫内膜癌（EC）和非典型子宫内膜增生（AEH）对于确定最佳手术治疗至关重要。然而，AEH 的术前诊断与最终组织学之间存在差异。我们的目的是建立免疫组织化学标志物的聚类，以区分 AEH 和 1 级 EC。

方法

我们研究了 13 种免疫组织化学标志物（甾体受体、促凋亡/抗凋亡蛋白、金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）以及 CD44 异构体），这些标志物已知在子宫内膜病理中具有作用。我们使用有监督的聚类确定了最有助于区分 1 级 EC 和 AEH 的共表达蛋白聚类。

结果

从 42 个组织样本（20 个 EC 和 22 个 AEH）中，我们发现了 3 个共表达蛋白聚类：聚类 1 包括 3 种蛋白（与 AEH 相比，1 级 EC 中 MMP-9 过表达，雌激素受体（ER）和孕激素受体（PR）A 表达下调）；聚类 2 显示 MMP-9 过表达和 ER 下调；聚类 3 显示 MMP-9、bcl-2 过表达和 ER、PR A 和 CD44-v6 变体下调。这三个聚类共同预测 1 级 EC 的错误分类率为 8%。