Elevated expressions of SHP2 and GAB2 correlated with VEGF in eutopic and ectopic endometrium of women with ovarian endometriosis

Abstract

Aims: Protein tyrosine phosphatase Src-homology-2-domain-containing phosphatase 2 (SHP2) and adaptor protein Grb2-associated binding protein 2 (GAB2) can bind to each other in various signal transduction. However, the expression of SHP2 and GAB2 have not been investigated in endometriosis. The aim of the study was to evaluate the expressions of SHP2 and GAB2, and explore the correlation with Ki67 and VEGF in ovarian endometriosis.

Materials and methods: The protein expressions and localizations were assessed immunohistochemically in ectopic, eutopic endometrium and normal endometrium from patients with (n = 30) and without (n = 30) ovarian endometriosis.

Results: SHP2 was mainly present in the endometrial glandular epithelium, with increased expression in eutopic endometrium and even higher expression in ectopic endometrium compared to control endometrium (p < .05). GAB2 was immunolocalized in endometrial epithelium and stroma, increasing its expression from control endometrium to eutopic and ectopic endometrium (p < .05). Positive correlation was found between SHP2 and GAB2 in endometrium (p < .01). SHP2 and GAB2 both positively correlated with VEGF (p < .05), but not Ki67 in endometrium.

Conclusions: We provide the first evidence that the protein expressions of SHP2 and GAB2 were elevated in ectopic and eutopic endometrium, suggesting GAB2-SHP2 axis regulating VEGF might contribute to the pathomechanism of endometriosis.

摘要

目的：蛋白酪氨酸磷酸酶含 Src 同源区 2 结构域磷酸酶 2 (SHP2) 和接头蛋白Grb2相关结合蛋白2 (GAB2) 可以在多种信号转导中相互结合。然而, SHP2和GAB2在子宫内膜异位症中的表达尚未见报道。本研究的目的旨在评价SHP2、GAB2在卵巢子宫内膜异位症中的表达, 并探讨其与Ki67、VEGF的相关性。

材料和方法：用免疫组织化学方法对卵巢子宫内膜异位症患者 (n=30) 和非卵巢子宫内膜异位症患者 (n=30) 的异位内膜、在位内膜和正常内膜中的蛋白表达和定位进行了评估。

结果：与对照相比, SHP2主要存在于子宫内膜腺上皮, 在在位内膜中表达增强, 异位内膜中表达更高 (p<0.05)。GAB2免疫定位于子宫内膜上皮和间质, 从对照子宫内膜到在位内膜和异位内膜, GAB2的表达逐渐增强 (p<0.05)。SHP2与GAB2在子宫内膜中的表达呈正相关 (p<0.01)。子宫内膜SHP2、GAB2与VEGF呈正相关(p<0.05), 与Ki67无相关性。

结论：首次证实异位内膜和在位内膜中SHP2和GAB2蛋白表达升高, 提示GAB2-SHP2轴调节VEGF可能参与了子宫内膜异位症的发病机制。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• SHP2
• GAB2
• endometriosis
• immunohistochemistry
• VEGF

Disclosure statement

The authors declared no conflicts of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [81671426 and 81901454] and the Medical Health Science and Technology Project of Zhejiang Province under Grant [2019RC045]