Introduction Endometrial carcinoma is one of the most common invasive tumours of the female genital tract and accounts for about 7% of all invasive cancers in women. 1 It is the 5th most common cancer of women worldwide. 2 An earlier retrospective statistical study showed that endometrial carcinoma with 86 out of 2223 cases formed 3.87% of all malignant neoplasms in females. 3 A collective Pakistani cancer registry (1994-2011) reported 707 cases of malignancies of corpus uteri contributing 3.02% of all neoplasms in females above 18 years of age. 4 A hospital-based registry showed that in 2010, out of 76 malignancies of the corpus uteri 65 (85.52%) were endometrial adenocarcinomas. 5 Endometrial carcinomas have been classified into two main types; type 1 and type 2, on the basis of light microscopic appearance, clinical behaviour and epidemiology. Type 1 and type 2 tumours carry mutations of independent set of genes. Endometroid (type 1) endometrial carcinoma is often preceded by a characteristic histopathologic lesion designated endometrial hyperplasia. Endometrial hyperplasia is usually associated with prolonged unopposed oestrogen stimulation and is characterised by increased gland-to-stroma ratio and abnormalities of epithelial growth relative to normal endometrium. The much debated World Health Organisation (WHO) classification of endometrial hyperplasia divides it into 4 types depending on architectural changes and cellular atypia. 6 These are: Simple hyperplasia without atypia; Complex hyperplasia without atypia; Simple hyperplasia with atypia; and Complex hyperplasia with atypia. Atypical hyperplasia has long been considered a precursor lesion for endometrial carcinoma. However endometrial hyperplasias are among the most commonly over-diagnosed lesions in surgical pathology. 7 Whether hyperplasia without atypia poses a potential risk for developing into endometrial carcinoma is still not clear. However, prolonged unopposed oestrogen exposure is seen to confer a 2-10 fold increased risk for endometrial carcinoma. 8-10 In cases of non-atypical hyperplasias, the recommended treatment is cyclical progestins therapy, Vol. 64, No. 10, October 2014 1103 ORIGINAL ARTICLE Differential expression of Phophatase and Tensin Homologue in normal, hyperplastic and neoplastic endometrium Summayya Shawana, 1 Shahnaz Imdad Kehar, 2 Fouzia Shaikh 3 Abstract Objectives: To observe the differential expression of phophatase and tensin homologue in normal proliferative, hyperplastic and malignant endometrial lesions. Methods: .The retrospective study was based on the analysis of endometrial samples, both hysterectomies and curettage, received at the department of pathology Basic Medical Sciences Institute at the Jinnah Postgraduate Medical Centre, Karachi, from January 1, 2006 to December 31, 2010. A total of 55 endometrial samples were analysed for morphological features and results of immunohistochemical staining. Results: Of the 55 samples, 25 (45.45%) were malignant endometrial lesions, 6 (10.9%) complex hyperplasias with atypia, 14 (25.45%) complex hyperplasias without atypia hyperplasia, 6 (10.9%) simple hyperplasias without atypia, and 4 (7.27%) normal proliferative endometrium. Among malignant endometrial lesions, 12 (48%) showed complete loss of phophotase and tensin homologue expression out of which majority were endometroid adenocarcinoma. Five (83.3%) cases of complex hyperplasias with atypia and 9 (64.28%) cases of complex hyperplasia without atypia showed complete loss of or diminished expression of phophotase and tensin homologue. Conclusion: Loss of phophotase and tensin homologue expression was seen in a significant number of well differentiated endometrial adenocarcinomas and complex hyperplasias with atypia suggesting loss of PTEN expression as an early event in endometrial carcinogenesis. Keywords: Endometrial carcinoma, Hyperplasia, PTEN expression, Atypia, Early event. (JPMA 64: 1103; 2014) 1 Bahria University Medical and Dental College, 2 Basic Medical Sciences Institute, JPMC, 3 Ziauddin University Medical College, Karachi. Correspondence: Summayya Shawana. Email: shawana75@yahoo.com