Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%–30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A -catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas. 1. Introduction Endometrial cancer is the most common cancer of the female reproductive tract with 150,000 new cases diagnosed annually worldwide. Approximately 90% of endometrial cancers are sporadic, and the remaining 10% are hereditary. Bokhman have generally categorized endometrial cancer into two broad groups of tumors using both clinical and histopathological variables: estrogen-dependent endometrioid endometrial carcinomas (EECs), or type I, and non-endometrioid endometrial carcinomas (NEECs), or type II tumors (Table 1) [1]. It should be noted that this model is not strict, and only a minority of endometrial cancer may exhibit shared characteristics. For example, mixed serous and endometrioid tumors are being increasingly recognized. Approximately 70% to 80% of new cases are classified as EECs, and other 10% to 20% are designated as NEEC tumors [1]. EECs are strongly associated with the estrogen-related pathway and arise in association with unopposed estrogen stimulation [2]. In contrast, NEECs are unrelated to the estrogen pathways and arise in the background of atrophic endometrium [3]. EECs typically occur in premenopausal and younger postmenopausal women and are usually low-grade and have a favorable outcome, whereas NEECs occur in older postmenopausal
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