Gungorduk K.Ertas I.E.Sahbaz A.Ozvural S.Sarica Y.Ozdemir A.Sayhan S.Gokcu M.Yilmaz B.Sanci M.Inan S.Harma M.Yildirim Y.2024-07-222024-07-22201403012115http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/16950Objective: 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. © 2014 Elsevier Ireland Ltd. All rights reserved.EnglishAdultAgedCarcinoma, EndometrioidDisease-Free SurvivalEndometrial HyperplasiaEndometrial NeoplasmsEndometriumExtracellular Signal-Regulated MAP KinasesFemaleFollow-Up StudiesHumansImmunohistochemistryMiddle AgedPhosphorylationPrognosisProto-Oncogene Proteins c-aktformaldehydemitogen activated protein kinase 1mitogen activated protein kinase 3paraffinprotein kinase Bmitogen activated protein kinaseprotein kinase Badultadvanced canceradvanced stage endometrioid endometrial adenocancerarticlecancer prognosiscancer stagingcancer survivalclinical articlecontrolled studyearly cancerearly stage endometrioid endometrial adenocancerendometrioid carcinomaendometrioid endometrial adenocancerendometriumendometrium biopsyendometrium carcinomaendometrium hyperplasiaenzyme phosphorylationfemalefollow uphumanhuman tissuehysterectomyimmunohistochemistryimmunolocalizationlymph nodelymph node metastasislymph vessel metastasismenopausemetastasismiddle agedmyometrial invasionoverall survivalpriority journalprogression free survivalprotein expressiontumor volumeadvanced cancerArticlecancer classificationcancer diagnosiscancer prognosiscancer surgerycurettagedifferential diagnosisendometrioid carcinomaendometriumendometrium carcinomaendometrium hyperplasiaageddisease free survivalendometrioid carcinomaendometrium hyperplasiaendometrium tumormetabolismpathologyphosphorylationprognosisArticle10.1016/j.ejogrb.2014.05.040