ERM/ETV5 and RUNX1/AML1 expression in endometrioid adenocarcinomas of endometrium and association with neoplastic progression

Abstract

The majority of endometrioid endometrial carcinomas (EEC) is diagnosed at stage I. Among these, 30% present myometrial invasion (stage IB), which is associated with tumor spread and relapse after primary treatment. Although an increased expression of RUNX1/AML1 and ERM/ETV5 in EEC have been suggested to be associated with early events of myometrial infiltration, there is no data regarding its expression along the evolution of EEC and possible associations with other clinicopathological parameters. Therefore, ERM/ETV5 and RUNX1/AML1 protein and gene expression profiles were assessed in different EEC stages to evaluate their role in endometrial carcinogenesis. RUNX1/AML1 and ERM/ETV5 proteins were analyzed by immunohistochemistry in 219 formalin fixed paraffin embedded endometrioid tumors and in 12 normal atrophic and proliferative endometrium samples. RUNX1/AML1 and ERM/ETV5 genes expression were analyzed by RT-qPCR. RUNX1/AML1 and ERM/ETV5 expression were decreased with increasing EEC stage, with a positive correlation between protein and gene expression for ERM/ETV5, but not for RUNX1/AML1. Both proteins were present in the nucleus of the tumor cells, whereas RUNX1/AML1, but not ERM/ETV5, was expressed in 7 out of 12 normal endometrial samples, with its expression being restricted to the cytoplasm of the positive cells. We concluded that there is a higher expression of ERM/ETV5 in early stages of EEC, whereas there seems to be a RUNX1/AML1 translocation from cytoplasm to nucleus in EEC neoplastic transformation.

ETS variant 5 promotes colorectal cancer angiogenesis by targeting platelet‐derived growth factor BB

“…It has been reported that high levels of ETV5 facilitate tumor cell proliferation, epithelial-mesenchymal transition (EMT), and metastasis in ovarian and prostate cancers. 26,27 ETV5 has also been shown to trigger the transcription of MMP-2, TIMP, and other proteinases to modify the extracellular matrix in human chondrosarcoma. 28 Additionally, previous studies have indicated that other ETS members, such as ETS1, ETS2, ETV2 and ETV4 regulate tumor angiogenesis.…”

An active RUNX1-ID1/ID3 axis governs differentiation and chemoresistance of cancer stem cell population in epithelial ovarian cancer cells

“…Runt related transcription factor 1 (RUNX1), an important molecule in etiology of leukemogenesis has been shown to play important role in tumor initiation and progression of solid tumors such as pancreatic cancer (Cheng et al, 2017;Liu et al, 2020), gastric cancer (Mitsuda et al, 2018), uterine cancer (De Sousa et al, 2014;Planaguma et al, 2011), ovarian cancer (Ge et al, 2014;Keita et al, 2013), triple-negative breast cancer (Ferrari et al, 2014), oral and skin squamous cell carcinoma (Sarper et al, 2018;Scheitz et al, 2012). RUNX1 is known to promote tumor metastasis by activating Wnt/β-catenin pathway in colorectal cancer (Li et al, 2019).…”

FN1 promotes prognosis and radioresistance in head and neck squamous cell carcinoma: From radioresistant HNSCC cell line to integrated bioinformatics methods

“…In HNSCC, Study from Yoon et al ( Yoon et al, 2015 ) proved that SOX4 may serve as an oncogene and causes radioresistance. E26 transformation-specific (ETS) transcription factors including ETV5, play important roles in tumor cell invasion, differentiation and angiogenesis ( de Sousa et al, 2014 ). It has been reported that high levels of ETV5 facilitate tumor cell proliferation, epithelial-mesenchymal transition, and metastasis in ovarian and colorectal cancers ( Llauradó et al, 2012 ; Cheng et al, 2019 ).…”