Tumor-associated macrophages, epidermal growth factor receptor correlated with the triple negative phenotype in endometrial endometrioid adenocarcinoma

Abstract

It has been well established that tumor-associated macrophages (TAMs) play a tumor-promoting role in endometrial endometrioid adenocarcinoma (EEC). However, the association with TAMs and the triple-negative phenotype (TNP) in EEC has not yet been reported. We used immunohistochemistry to examine the expression of CD68, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in 186 cases of EEC. Fluorescent in situ hybridization (FISH) was also used for HER2 amplification, and the association with TAMs count, EGFR expression, and triple-negative phenotype was analyzed. Twenty-eight of 186 patients (15.05%) had the TNP. It was associated with advanced stage disease (P<0.0001), high grade disease (P<0.0001), depth of myometrial invasion (P=0.003), pelvic lymph node metastasis (P<0.001), lymphovascular space invasion (P=0.001), and EGFR expression (P=0.032). Margin TAMs count was also significantly increased in the TNP-positive group, the EGFR-positive group, and the PR-negative group (P<0.001, respectively). The TNP was associated with a significantly worse overall survival (OS) (log rank test, P=0.018). The estimated 5-year OS of patients with TNP was 59.1%, while that without TNP was 78.5%. Multivariate analysis showed high margin TAMs, and the histopathological grades were significantly associated with OS. The TNP in EEC is associated with poor prognostic surgical–pathological factors, worse prognosis, as well as with high margin TAMs and overexpression of EGFR, which may serve as potential targeted therapies for the special phenotype in EEC.