However, it has been recently reported that PTEN

mutations are more frequent in low-grade endometrial EMA (67%) compared with low grade ovarian EMA (17%); contrastingly, CTNNB1 mutations are significantly different in low-grade ovarian EMA (53%) compared with low-grade endometrial EMA (28%).[56] This type of endometrial carcinoma typically has papillary growth and is comprised of atypical cells showing a high nucleus/cytoplasm ratio and high mitotic Apitolisib in vitro count. These cells are tufting and budding, and may often form glands. The background endometrium is usually atrophic. SEA typically displays the significant overexpressions of p53 and p16. Overexpression of p16 is thought to be due to dysregulation of the p16INKA/cyclin D-CDK/pRb-E2F pathway.[57-59] ER is usually diminished or negative, the

same as PgR. PTEN and ARID1A expressions are retained. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is overexpressed typically in embryonic tissue.[60-62] These results suggest that IMP3 is associated with cell migration and tumor Crizotinib concentration invasion.[60, 63] The significant expression of IMP3 in SEA is, therefore, considered to be related to its development and aggressive clinical behavior.[63-65] SEA of the corpus and ovary share a considerable number of similar characteristics. But, as with WT-1, SEA of the ovary diffusely shows the expression in a frequency of 70–80%, and SEA of the endometrium is less frequently positive, at no more than 20–30%.[66-68] Endometrial intraepithelial

carcinoma (EIC), which is considered as a putative precursor of SEA,[69-71] usually occurs in the setting of inactive or resting endometrium and frequently involves endometrial polyps.[72] Many of minimal SEAs, defined as limited to the endometrium and less than 1 cm, are also frequently found to have EIC and involve endometrial polyps.[73] However, the nomenclature of EIC remains controversial because there are morphological variations in the endometrial intraepithelial precancerous Avelestat (AZD9668) lesions. Therefore, instead of EIC, a newly defined terminology of endometrial glandular dysplasia has been proposed.[74] EIC is known to be potentially complicated with extrauterine lesions. The 10–34% of endometrial carcinomas in postmenopausal women have been reported to be associated with endometrial polyps, and the majority of them are the most common type EMA, with the second most common type being SEA.[75] These EICs show frequent p53 mutation with the ratio ranging 63–72%.[76] The labeling index of Ki-67 is approximately 40%, and ER and PgR are exceptionally expressed but not significantly.[72] CCA of the uterine corpus is also categorized as type II, but is not as frequent as SEA.[10, 11] Histologically, the CCA cells show papillary, tubular, tubulocystic and solid architecture, and possess polygonal nuclei with typically clear cytoplasm.