Uterine Serous Carcinoma; Molecular Pathways and Role of Micrornas in Early Detection and Target Therapy

As a high grade tumor, uterine serous carcinoma (USC) accounts for less than 10% of endometrial carcinomas (EC), but in association with endometrial clear cell carcinoma (CCC) and grade 3 endometrioid carcinoma is responsible for 70-75% of EC deaths [1] and per se accounts for 39% of this cancer related deaths [2]. As a prototype of type II endometrial carcinoma, USC is an aggressive disease and near 60-70% of the patients present with extrauterine spread at the time of diagnosis [2]. In contrast with more common type I endometrial carcinoma, serous carcinoma tends to occur in older age group and usually diagnosed at advanced stages [3]. Even among women who have not myometrial invasion, 33-50% of them will show extrauterine spread in comprehensive staging [4]. Its tendency for early spread, leads to upstaging of 50-70% of clinically stage I cancers at the time of operation [5]. Presentation of 46% of patients with USC and endometrial clear cell carcinoma in stage II-IV compared to 21% for all endometrial cancers confirms the common perception that these histotypes carry a worse prognosis due to advanced disease at the time of diagnosis [6]. Although the term “Endometrial Intraepithelial Carcinoma”(EIC) is widely used to designate the precursor lesion of uterine serous carcinoma, it should be acknowledged that “early serous carcinoma” or other alternative diagnostic terms have been suggested for use in clinical practice, in recognition that some serous carcinomas without invasion in the uterus are associated with extra-uterine spread [7,8]. For this reason Clement and Young considered EIC (Figure1) as a tiny focus of serous carcinoma and did not qualify it further other than to note its size and location and stressed Abstract