In this study, we used tissue microarrays to demonstrate that Trop-2 protein overexpression is significantly associated with higher tumor grade as well as cervical involvement and serves as an independent prognostic factor for DFS in EEC. A trend towards significance between Trop-2 expression and OS and PFS was exhibited and would likely have been achieved for OS with larger sample size or longer median follow-up, as greater time is required to demonstrate differences in OS compared to other endpoints . Nevertheless, DFS has been shown to be highly correlated with OS and is increasingly received as an acceptable endpoint . These findings are consistent with previous reports that suggest that Trop-2 overexpression identifies biologically aggressive phenotypes and poorly differentiated disease [24, 28–31]. Though Trop-2 has been shown to be an excellent candidate antigen for targeted immunotherapy in multiple gynecologic malignancies including EEC , uterine papillary serous carcinomas , chemotherapy-resistant  and sensitive ovarian carcinomas , and cervical carcinomas , this is the first proof that Trop-2 overexpression can also prognosticate patient outcome in EEC.
The role of Trop-2 in cancer pathogenesis remains incompletely elucidated. In accordance with its original identification in trophoblasts, which possess the capacity to invade uterine decidua during the process of placental implantation, Trop-2 may analogously confer to cancer cells the capacity for proliferation and invasion [36, 37]. Wang et al. (2008)  demonstrated the role of Trop-2 in anchorage-independent growth and the oncogenic potential of Trop-2 in colon cancer cells using both in vitro and in vivo models. Trop-2 has been shown to directly mediate tumor-associated calcium-mediated signal cascades  and activation of ERK 1/2-MAPK pathways , both of which govern cell cycle progression [40, 41] and may protect cancer cells from apoptosis . A highly conserved phosphatidylinositol 4,5-bisphosphonate (PIP2) binding sequence that overlaps with a protein kinase C phosphorylation sites within the cytoplasmic tail suggests a specific role in signal transduction [43, 44]. Recently, Trerotola et al.  demonstrated that Trop-2 upregulation is necessary and sufficient to promote cell growth in different cancer cell types and that its somatic knockdown is able to extinguish tumor cell growth. The Trop-2 transcription control network, including factors activating Trop-2 expression or downstream growth-stimulatory pathways has been recently reported . Interestingly, Trop-2-cyclin D1 chimeric mRNAs have also been identified in a variety of tumors and appear to lend enhanced stability to cyclin D1, resulting in cellular immortalization  and possibly prevention of anoikis . Of note, Trop-2 expression appears to discriminate populations with stem-like activity , which may be important for initiation and perpetuation of cancers [50, 51]. A different role of Trop-2 in cancer growth has been recently reported by Lin et al.  in lung carcinoma, where Trop-2 is epigenetically downregulated and affected by LOH, resulting in cancer progression via activation of IGF-1R signalling.
In this report, we provide immunostaining results indicative of protein expression. Immunohistochemistry is widely accepted as an adjunct technique to routine histologic analysis to offer additional diagnostic and prognostic information . We did not evaluate Trop-2 at the mRNA level since transcript copy number and protein expression are poorly concordant for this antigen . This phenomenon is not uncommon; genomic analyses at best are believed to capture only 40% of proteomic variations due to post-transcriptional regulatory mechanisms in mammalian cells .
Generally accepted prognostic factors for endometrial carcinoma are nodal involvement/stage, grade, and histologic subtype . As anticipated, in this cohort Trop-2 overexpression correlated with grade and propensity for cervical involvement. Tumor location within the uterus has potential clinical relevance, since the lymphatic drainage of the cervix differs from that of the fundus in that it is much more rich and tends to involve the pelvic as opposed to the para-aortic nodes .
Many recent attempts to discover novel prognostic factors for endometrial cancer have been discouraging. Koyuncuoglu et al. (2012)  described the loss of e-cadherin expression in association with advanced stage and poor differentiation in both EEC and non-EEC, but failed to demonstrate statistical significance between e-cadherin levels and survival using multivariate analyses. Similarly, while Mhawech-Fauceglia et al. (2012)  noted a high percentage of uterine papillary serous and EEC cases with expression of the tight junction protein claudin-7 and the cytoskeletal protein moesin, no association existed between these proteins and overall or disease-free survival.