Forkhead box M1 over-expression and dachshund homolog 1 down-regulation as novel biomarkers for progression of endometrial carcinoma in Egyptian patients.

Abstract

IntroductionForkhead box M1 (FOXM1) is considered as a novel anti-cancer target, because it has many essential functions such as mitosis regulation, cell cycle transition, and other carcinogenesis signaling pathways. Dachshund homolog 1 (DACH1) is a member of the Sno/Ski co-repressor family.Material and methodsExpression of DACH1 has been detected in many cancers. Patients and pathologic specimens: 50 patients with endometrial cancer (EC) were included in the study: ten specimens of normal endometrium and twenty specimens of endometrial hyperplasia. All samples underwent processing to investigate FOXM1 and DACH1 expression using immunohistochemistry.ResultsFOXM1 expression was detected in EC tissues more than normal endometrium and endometrial hyperplasia tissues (p = 0.001) and 0.01. Increased FOXM1 expression was positively associated with larger tumor size (p = 0.002), high grade (p = 0.004), myometrial invasion, presence of lymph node metastases, higher Federation of Gynecology and Obstetrics (FIGO) stage (p < 0.001), and worse progression-free survival (PFS) and overall survival (OS) rates. The expression of DACH1 was lower in EC cells than normal endometrium and endometrial hyperplasia tissues (p = 0.071) and 0.252. Low DACH1 expression was associated with high grade (p = 0.001), presence of lymph node metastases (p = 0.49), higher FIGO stage (p = 0.022), and unfavorable PFS and OS rates (p = 0.037). We found an inverse association between expression of FOXM1 and DACH1 in EC tissues and in non-neoplastic endometrial tissues (p = 0.007).ConclusionsFOXM1 over-expression and DACH1 down-regulation in EC were related to poor clinical and pathological parameters and unfavorable prognosis.