Immunohistochemical expression of phosphatase and tensin homolog in endometrial hyperplasia and carcinoma Afaf T. Elnashar a , Sanaa M. Sotohy a , Eman M.S. Muhammad a , Noha Eldabie a and Mahmoud Sabry b Introduction The phosphatase and tensin homolog (PTEN) gene is localized on chromosome 10q23. It is a tumor suppressor gene that inhibits cell proliferation by regulating intracellular signaling pathways, and this activity can be abolished by mutations of the PTEN gene. PTEN is frequently mutated in a wide range of human tumors. Aim of the study In this study, we evaluated the use of PTEN gene as a diagnostic marker to differentiate between endometrioid adenocarcinoma and premalignant lesions of the endometrium. Materials and methods We used an immunohisto- chemical technique to evaluate the alteration of PTEN in 53 biopsy cases of normal, hyperplastic, and neoplastic endometrial tissue. Results We found that PTEN expression was decreasing from hyperplasia (seven of 12 cases) to atypical hyperplasia (three of six cases), to endometrioid carcinoma (six of 21 cases), with statistically significant relationships. Conclusion PTEN alteration of expression is one of the earliest changes in the process of endometrial tumorigenesis from hyperplasia to the carcinoma stage. Egypt J Pathol 31:2–5  c Egyptian Journal of Pathology Egyptian Journal of Pathology 2011, 31:2–5 Keywords: atypical hyperplasia, endometrioid carcinoma, phosphatase and tensin homolog a Department of Pathology, Sohag University and b Department of Obstetric and Gynecology, Sohag University Hospital, Sohag, Egypt Correspondence to Afaf T. Elnashar, Department of Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt Tel: +2 0164641550; fax: +2 0934602963; e-mail: elnasharafaf@yahoo.com Received 3 December 2010 Accepted 2 February 2011 Introduction Endometrioid endometrial adenocarcinoma accounts for three fourths of the endometrial cancers and are thought to develop after a continuum of premalignant lesions ranging from endometrial hyperplasia without atypia to hyperplasia with atypia and finally to well-differentiated carcinoma (Boruban et al., 2008). Accurate diagnosis of premalignant lesions in routine endometrial biopsies has a great clinical value in their management. Unfortunately, several recent studies have shown that cytological atypia, which is an important criterion for diagnosis of premalignant lesions (atypical hyperplasia), has poor reproducibility. Therefore, new insight into the morphology of biologically defined precancerous lesions of the endometrium is needed (Mutter, 2002). Endometrioid endometrial adenocarcinoma has a variety of genetic alterations, including microsatellite instability, and mutations of phosphatase and tensin homolog (PTEN), K-ras, and B-catenin genes. These molecular genetic alterations have been described in atypical endometrial hyperplasia. PTEN is the most frequently altered gene in endometrioid carcinoma. Up to 50% of all endometrioid adenocarcinomas and 83% of tumors with adjacent premalignant lesions show altered PTEN that is characterized by loss of expression (Liu, 2007; Kapucuoglu et al., 2007). Mutations of PTEN are frequently detected in several cancers such as ovary (Geyer et al., 2009), prostate (Visakorpi, 2003), breast (Bose et al., 2002), glial tumors (Kimura et al., 2004), and endometrium (An et al., 2002). Loss of PTEN expression is detected in a diffuse pattern in endometrial carcinoma, but also may be detected focally in morphologically normal endometrial tissue. This suggests that PTEN alteration occurs in the earliest phase of endometrial carcinogenesis (Lacey et al., 2008). The hypothesis that loss of PTEN expression could be assessed by immunohistochemical method has led to the use of PTEN immunostaining for the diagnosis of malignant and premalignant lesions (Pallares et al., 2005). In this study, we used an immunohistochemical method to evaluate PTEN expression in normal, hyperplasia, and carcinoma of the endometrium. Materials and methods Fifty three samples were retrieved from the Pathology lab of the Sohag University Hospital. They were previously diagnosed as: simple endometrial hyperplasia (8), Com- plex hyperplasia without atypia (12), complex hyperplasia with atypia (6) and endometrioid adenocarcinoma (21). All Grades of endometrial carcinoma were represented (G1-12) (G2-3) and (G3-6). They were all selected from Surgical Pathology files of the Department of pathology, Sohag University Hospital during the period from January 2007 to December 2008. The samples included 32 curettage and 21 excisional biopsies. Hematoxylin and eosin-stained sections from each case were reviewed by two pathologists to con- firm the histological diagnosis according to WHO histo- logical classification. Specimens with any evidences of 2 Original article 1687-4277  c 2011 Egyptian Journal of Pathology DOI: 10.1097/01.XEJ.0000398104.35275.62 Copyright © Egyptian Journal of Pathology. Unauthorized reproduction of this article is prohibited.