Tumor budding and E-Cadherin expression in endometrial carcinoma: Are they prognostic factors in endometrial cancer? Meral Koyuncuoglu a , Emre Okyay b, ⁎, Bahadir Saatli b , Safak Olgan b , Mustafa Akin c , Ugur Saygili b a Dokuz Eylul University School of Medicine, Department of Pathology, Izmir, Turkey b Dokuz Eylul University School of Medicine, Department of Obstetrics and Gynecology, Izmir, Turkey c Mustafa Kemal University School of Medicine, Department of Pathology, Hatay, Turkey abstract article info Article history: Received 31 August 2011 Available online 22 December 2011 Keywords: Endometrial carcinoma Budding E-cadherin Prognosis Objective. To evaluate the prognostic value of tumor budding (TB) in endometrioid (EEC) and non- endometrioid endometrial cancers (NEEC) and to determine its correlation with expression of E-cadherin. Methods. Ninety-five patients with primary endometrial carcinoma were examined statistically. All pa- tients were diagnosed, treated, and given follow-up care at Dokuz Eylul University Faculty of Medicine. Tumor budding detected by either H&E-stained sections and anticytokeratin-staining C11. The tissue block with the largest invasive front was chosen for budding counting and immunostaining. E-cadherin expression was examined by immunohistochemistry using the primary antibodies against to it. Results. Tumor budding was low-grade in 73 and high-grade in 22 cases. E-cadherin expression loss was identified in 48 patients. The high-grade TB was significantly higher in patients with advanced stage and deep myometrial invasion (p = 0.032 and 0.018, respectively). E-Cadherin expression was significantly lower in NEECs than EECs (p = 0.032). The negative expression of E-cadherin was associated with advanced stage and poor differentiation (p = 0.001 and p = 0.024, respectively). We determined that tumor budding ad- versely correlated with the presence of E-cadherin expression but not statistically significant. Based on the results of multivariate analysis, TB has an independent impact on cumulative overall survival. We found no statistically significant difference between E-cadherin expression and survival. Conclusions. TB is associated with undifferentiated tumor, advanced stage and decreased postoperative survival in endometrial cancer. It might be a valuable prognostic clinicopathologic factor which can be appli- cable in routine examination. © 2011 Elsevier Inc. All rights reserved. Introduction Endometrial cancer is the most common malignancy of the female reproductive tract in developed countries and overall survival is rela- tively higher compared with other gynecologic malignancies [1]. It can be classified into two major clinicopathologic types; endome- trioid carcinomas (EECs) and non-endometrioid endometrial carcino- mas (NEECs), including papillary, serous or clear cell histology. The patients with NEECs have a worse prognosis due to increased tenden- cy of these tumors to extend out of uterus at the time of diagnosis. In contrast, the majority of endometrioid endometrial carcinomas (EECs) are confined to the uterus and their prognosis are usually well [2]. Tumor budding is a histopathological feature that can be easily identified by using routine pathologic examination, which is observed in the front of invasive margin of the tumor. It is described as an iso- lated single cancer cell or microscopic small cell clusters composed of b 5 cells found outside the invasive margin of a tumor [3]. It has been proposed as one of potential prognostic biological variables in various cancers. In previous studies, it has been determined that this patho- logic entity is related to lymph node status, local recurrence and poor prognosis, particularly in colorectal carcinomas, as well as anal, lung and esophageal carcinomas [4–7]. However, there was no estab- lished precise standard criteria for the assessment of tumor budding. While some researchers have classified the tumor budding as none, mild, moderate and severe, the other ones as according to presence or absence, or marked and non-marked [7–9]. This entity appears to be associated with two main events in invasion and metastasis of tumor; abnormal cell differentiation and loss of cell–cell adhesion [10]. Cell to cell adhesion is mainly mediated by cadherins which are transmembrane glycoproteins that join adjacent epithelial cells using a calcium-dependent binding mechanism [11]. Also it has been found that the loss of cell to cell adhesion is associated with de- creased E-cadherin expressions in epithelial tumor cells [12]. Al- though, there are different molecular alterations between two types of endometrial cancer, more aggressive behaviors of NEECs might be due to decreased intercellular cohesiveness in these tumors. Many studies showed that decreased expression of cadherin facilitated Gynecologic Oncology 125 (2012) 208–213 ⁎ Corresponding author at: Department of Obstetrics and Gynecology, Dokuz Eylul University School of Medicine, 35340, Balcova, Izmir, Turkey. Fax: + 90 232 412 2198. E-mail address: dremreokyay@hotmail.com (E. Okyay). 0090-8258/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2011.12.433 Contents lists available at SciVerse ScienceDirect Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno