Editor—Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in the United States and other western countries.1 Although several genes may be altered in these cancers,2 the molecular events in the development of endometrial carcinoma remain poorly defined. Changes in simple sequence repeats in tumour DNA relative to normal DNA, referred to as microsatellite instability (MSI), are a feature of many endometrial carcinomas.3-7 MSI occurs as a result of failing DNA mismatch repair8 and is known to accompany defects in the MLH1,MSH2, MSH6,MSH3, PMS2, and possibly PMS1 genes. Apart fromMSH3, all these genes are associated with inherited cancer susceptibility in the context of hereditary non-polyposis colorectal cancer (HNPCC).3 9-16Endometrial carcinomas are the most common extracolonic cancers in HNPCC17 and usually occur at an early age.18Women who carry HNPCC mutations have a 22-43% lifetime risk of developing endometrial cancer as compared with 3% for the general population.19-21 According to a recent report, germline mutations of the DNA mismatch repair geneMSH6 might be specifically associated with susceptibility to endometrial cancer.22

PTEN is a newly isolated tumour suppressor gene located on chromosome 10q23, a region frequently deleted in multiple types of human cancer.23-25 Inactivation ofPTEN is the underlying cause of familial Cowden disease.26 Inactivating mutations in thePTEN gene are frequently found in multiple tumour types including brain, breast, prostate, endometrial, and skin carcinomas.23-25 Knockout mice forPTEN die as early embryos, while animals heterozygous for a mutant PTEN allele develop a broad spectrum of tumours.27-29 These observations have established that PTEN has multiple target organs including the endometrium.

Recent reports have shown that β-catenin is a multifunctional protein involved in …