HE4 in endometriod and non- endometrioid subtype of endometrial cancer does not mean the same

Objective: To study the association between the preoperative value of serum HE4 marker and poor histological prognostic factors depending on the subtype of endometrial cancer (EC): endometrioid and non-endometrioid tumors. Methods: Prospective and multicenter cohort study including patients with EC in Miguel Servet University Hospital of Zaragoza (Spain) and Hospital Clínico San Carlos of Madrid (Spain) from January 2017 to March 2020. Preoperative serum levels of HE4 were analyzed by clinical and pathological characteristics. Results: Overall, 190 patients were included. Of them, 158 were subtype I of EC and 32 were subtype II tumors. In endometrioid EC, a statistically significant association was found between the preoperative HE4 value and tumor size (p < 0.001), deep myometrial invasion (p = 0.001), lymphovascular space invasion (LVSI) (p = 0.002), cervical (p = 0.001), adnexal (p = 0.023), isthmus (p < 0.001) and parametrial involvement (p = 0.012), lymph node metastasis (p = 0.025) and FIGO stage (p < 0.001). On the contrary, no histological factors showed statistical association except LVSI (p = 0.025) in the non-endometrioid subtype. Conclusions: The preoperative value of HE4 is related differently with several established prognostic factors for EC according to the histological type of tumor. These results could be relevant in order to standardize a prognostic value of HE4 in EC.