In 2006, a definition of “precancer” in the majority of human organ sites was established by the National Cancer Institute-sponsored consensus conference [Link]. Intriguingly, EmGD turns out to meet all of the criteria included in the definition and fulfill the role to be the putative precancer to ESC [Yi and Fadare].
First, a precancer is different from the normal tissue from which it arises. EmGD is an identifiable entity with the nuclear atypia exceeding that of adjacent normal resting endometrium [Zheng].
Second, a precancer shares some but not all molecular and phenotypic properties that characterize the cancer. EmGD often develops in multicentric sites that are noncontiguous with the main tumor mass of ESC but often associated with serous EIC. No direct transitions are observed between EmGD and ESC. Cytologically, the degree of nuclear atypia in EmGD falls short of serous EIC, which is the main difference between EmGD and serous EIC [Zheng]. Molecular evidences show that the load of alternations increased from resting endometrium to EmGD to serousEIC and/or ESC as evidenced in LOH of TP53 and chromosome 1p [Liang], mutation rate of p53 [Jia] and IHC index of p53, MIB-1 and another new cytoplasmic marker called IMP3 [Zheng].
Third, the cancer arises from the cells within the precancer. In this study, at least one identical p53 gene mutation was found in lesions of EmGD and ESC or serous EIC within the same uterus in all the 6 cases. Such a high concordance demonstrates a monoclonal growth of ESC from precancer cells.
Fourth, there are methods by which precancer can be diagnosed. The diagnostic criteria have been described before. It is mainly based on morphologic changes under microscope by excluding serous EIC or clear cell EIC. IHC analysis of p53, IMP3 and MIB-1 is helpful when obscure judgment is encountered. More objective computerized karyometric analysis of H&E stained slides is being carried out to improve the reproducibility.
Finally, those precancer patients are associated with an increased risk of cancer. In our retrospective study, a 9-fold increased risk of developing ESC is observed in those with EmGD diagnosis [Zheng].