title: 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.
  
  
  METHODS
  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.
authors: Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Kemal
authors: K
authors: Gungorduk
authors: Department of Obstetrics and Gynecology, Tepecik Education and Research Hospital, Izmir, Turkey. Electronic address: drertas@gmail.com.
authors: Ibrahim Egemen
authors: IE
authors: Ertas
authors: Department of Obstetrics and Gynecology, Bulent Ecevit University, School of Medicine, Zonguldak, Turkey.
authors: Ahmet
authors: A
authors: Sahbaz
authors: Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Seyfettin
authors: S
authors: Ozvural
authors: Department of Histology and Embryology, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors: Yagmur
authors: Y
authors: Sarica
authors: Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Aykut
authors: A
authors: Ozdemir
authors: Department of Pathology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Sevil
authors: S
authors: Sayhan
authors: Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Mehmet
authors: M
authors: Gokcu
authors: Department of Obstetrics and Gynecology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Bulent
authors: B
authors: Yilmaz
authors: Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Muzaffer
authors: M
authors: Sanci
authors: Department of Histology and Embryology, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors: Sevinc
authors: S
authors: Inan
authors: Department of Obstetrics and Gynecology, Bulent Ecevit University, School of Medicine, Zonguldak, Turkey.
authors: Mehmet
authors: M
authors: Harma
authors: Department of Gynecologic Oncology, Tepecik Education and Research Hospital, Izmir, Turkey.
authors: Yusuf
authors: Y
authors: Yildirim
mesh_terms: D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D004714:Endometrial Hyperplasia / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK1/2; Endometrial hyperplasia; Endometrioid endometrial adenocancer; Immunolocalization; Prognosis; p-AKT