Early-stage EMCA with high risk features, such as deep myometrial invasion, lympho-vascular space invasion and high grade is associated with a 15–25% risk of recurrence. Adjuvant radiotherapy, the most common form of therapy for early-stage high risk patients, has been found in multiple studies to decrease pelvic and vaginal TWS119 recurrence from 12–14% without therapy to 3-4% with therapy, but still without a corresponding increase in overall survival. In other words, radiotherapy exposes a large number of women to toxicity without any clear benefit in overall mortality, especially the majority of patients who will be free of disease in the absence of additional therapy. Radiation therapy is also used for previously untreated patients with local/regional recurrence. However, despite radiation, 50% of patients with local recurrence will ultimately die of their disease, implying that these patients have radiation resistant tumors and may have benefitted from alternate treatment such as chemotherapy. Identifying markers of radiation sensitivity/resistance would allow for tailored therapy to the most effective regimen and decrease unnecessary radiation-induced toxicity. Yes-associated protein was first identified by virtue of its ability to associate with Yes and Src protein-tyrosine kinases. The YAP gene is located at human chromosome 11q22, encodes a transcriptional co-activator and is one of the two main downstream effectors of the Hippo tumor suppressive pathway. Inhibition of the Hippo pathway leads to YAP activation, nuclear localization and increased activity of transcriptional target genes, such as CTGF and AREG. The YAP serine 127 to alanine mutant is a constitutively active form that remains in the nucleus and is transcriptionally active. YAP regulates the balance between cell proliferation and apoptosis, and is amplified in a number of human malignancies including breast, esophageal, hepatocellular, ependymoma, malignant mesothelioma and medulloblastoma. In addition, YAP expression correlates with poor prognosis in various cancers, such as colorectal, esophageal, gastric, hepatocellular, lung and ovarian, There is also crosstalk between YAP and steroid hormones. Dhananjayan et al. demonstrated that YAP and the domain binding protein-2 are co-activators of ER and PR, which play a key role in the normal menstrual cycle and in the etiology of type 1 EMCA. Although several reports demonstrated oncogenic functions for YAP in various human cancers, its biological and clinical relevance in EMCA remains unclear. In addition, YAP overexpression promotes radioresistance in medulloblastoma cells through the YAP/IGF2/Akt pathway, suggesting YAP can function in modulating radiation sensitivity/resistance. Those findings urged us to further investigate whether YAP could play a role in oncogenesis and development of EMCA and modulation of radiation sensitivity. In the present study, we investigated the potential utility of YAP as a prognostic and therapeutic indicator in EMCA and the biological function of YAP in EMCA. Furthermore, we evaluated YAP effect regarding radiation sensitivity.