Immunolocalization of ERK1/2 and p-AKT in normal endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer and their prognostic significance in malignant group

Abstract

Objective: To analyze the expression patterns of extracellular signal-regulated kinase (ERK1/2) and phosphorylated (p)-AKT in the tissues of non-pathologic endometrium, endometrial hyperplasia, and early and advanced stage endometrioid endometrial adenocancer using indirect immunohistochemistry, and also to investigate the effect of ERK1/2 and p-AKT expression patterns on prognosis in endometrioid adenocancer.

Study design: Immunolocalization of ERK1/2 and p-AKT was examined in six different types of endometrial tissues: proliferative endometrium (PE; n=10, 11.2%), secretuar endometrium (SE; n=10, 11.2%), simple hyperplasia (SH; n=15, 16.9%), complex hyperplasia (CH; n=3, 3.4%) and atypical complex hyperplasia (ACH; n=10, 11.2%), which were obtained from endometrial biopsies, curettage materials, and hysterectomy specimens and classified as the benign group; and both early stage endometrioid (n=21, 23.6%) and advanced stage endometrioid adenocancer (AC; n=20, 22.5%), which were obtained from complete surgical staging materials and classified as the malignant group. All specimens were fixed in 10% formalin and processed using routine paraffin protocols. Immunostaining intensities were evaluated as negative or weak (assigned as low expression) and moderate or strong (assigned as high expression).

Results: In the malignant group, 23 of 41 patients (56.1%) had high ERK1/2 and p-AKT expression, whereas only three of 48 patients in the benign group (6.3%) had high ERK1/2 and p-AKT expression (P<0.0001 and P<0.0001, respectively). p-AKT expression was significantly higher in women with positive lymph nodes (OR 9.0; 95% CI: 1.2-100.0; P=0.03). Higher expression of p-AKT was significantly associated with poor progression-free survival (PFS) and overall survival (OS). In contrast, ERK1/2 expression was not associated with PFS or OS.Conclusions ERK1/2 and p-AKT can be useful in the differential diagnosis of benign vs. malignant endometrial lesions, as well as early vs. advanced stage endometrioid endometrial adenocancer. Additionally, higher p-AKT expression could be used as a marker of poor prognosis in the management of patients with endometrioid endometrial adenocancer.

Keywords: ERK1/2; Endometrial hyperplasia; Endometrioid endometrial adenocancer; Immunolocalization; Prognosis; p-AKT.