On the basis of our studies and available clinicopathologic evidence in the past years, we advocate a model for endometrial serous carcinogenesis. In this model, endometrial serous carcinoma arises predominantly in the resting endometrium, manifesting first as p53 immunoreactive, morphologically normal endometrial cells (p53 signature), evolving to endometrial glandular dysplasia (which is the first morphologically identifiable precursor lesion), then to serous endometrial intraepithelial carcinoma (a carcinoma with a noninvasive growth pattern in the uterus but which is frequently associated with extrauterine disease), and finally into fully developed serous carcinoma. The representative pathologic pictures for ESC and its precursors are illustrated in Figures 1 to 3.
There have been many molecular alterations in the evolution of the tumor. Some of these molecular events are also present in its putative precursor lesions, such as p53 and BRCA mutation, HER2/neu amplification, and the molecular changes of IMP3 and Nrf2, etc (Figure 4).