Review Article Insights into Endometrial Serous Carcinogenesis and Progression

摘要: Endometrial serous carcinomas (ESC) constitute only approximately 10% of endometrial cancers, but have a substantially higher case-fatality rate than their more common endometrioid counterparts. The precise composite factors driving carcinogenesis and progression remain largely unknown, we attempt to review the current state knowledge in this report. ESC probably do not evolve through single pathway, underlying molecular events occur early evolution. TP53 gene mutations 22.7 96% cases, p53 protein overexpression is seen 76%. By expression profiling, p16 upregulated significantly above both normal cells carcinomas, 92-100% cases display diffuse by immunohistochemistry (IHC). Together, these findings suggest dysregulation p16INKA/Cyclin D-CDK/pRb-E2F ARF-MDM2- cell cycle pathways ESC. IHC, HER2/neu overexpressed (2+ or 3+) 32.1% ESC, 54.5% scored as 2+ 3+ IHC c-erbB2 amplification assessed fluorescent situ hybridization. Genetic instability, typically manifested loss heterozygosity multiple chromosomes, feature one study found at 1p32-33 63% cases. A subset patterns that are characteristic high grade including metastasis suppressor CD82 (KAI-1) epithelial-to-mesenchymal transformation, latter E-cadherin downregulation, P-cadherin upregulation, transformation-related molecules such zinc-finger E-box-binding homeobox 1 (ZEB1) focal adhesion kinase. Preliminary data suggests differential some isoforms claudins, proteases, tumor invasiveness progression-associated oncofetal insulin-like growth factor II mRNA-binding 3 (IMP3), well variety other molecules. At morphologic level, evidence indicates glandular dysplasia (EmGD) most likely morphologically recognizable precursor lesion presented. We advocate use term intraepithelial carcinoma (EIC, its appellations) descriptor never diagnostic/pathologic statement biologic potential. Given potential for extrauterine extension, consider lesions described EIC, when present isolation, examples localized patients should be managed such. Morphologically normal, immunoreactive (the so-called "p53 signatures"), show statistically significant association with subset, form start model, outlined herein, from signatures EmGD conventionally invasive neoplasm. identification morphologically-recognizable holds promise detection attendant reduction overall associated mortality rate. Deciphering basis uncover targets diagnosis, therapy, and/or disease surveillance.