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

INTRODUCTION: Forkhead 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 METHODS: Expression 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. RESULTS: FOXM1 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). CONCLUSIONS: FOXM1 over-expression and DACH1 down-regulation in EC were related to poor clinical and pathological parameters and unfavorable prognosis.

Prognostic impact of Apaf-1, Cyclin D1, and AQP-5 in serous ovarian carcinoma treated with the first-line chemotherapy.

Chemoresistance is the major obstacle to effective treatment in patients with serous ovarian carcinoma (SOC), which frequently related to the failure of chemotherapeutic agents to induce apoptosis. In this study, the immunohistochemical expression of Apaf-1, Cyclin D1, and Aquaporin-5 (AQP-5) was studied in 50 paraffin blocks of SOC. Data on overall survival (OS), disease-free survival (DFS) and response to the first-line chemotherapy were collected and then statistically analyzed. Apaf-1 expression was observed in 84% of the SOC cases with a significant down-regulation with higher tumor grade, lymph node metastasis, and advanced FIGO stage. Cyclin D1 expression was found in 70% of the cases with a significant up-regulation with higher tumor grade, lymph node metastasis, and advanced FIGO stage. Positive AQP-5 expression was noted in 84% of the cases with a significant positive association with higher tumor grade, lymph node metastasis, and advanced FIGO stage. During the follow-up period, the Apaf-1 expression had a significant negative association with OS and DFS (p < 0.001 for each), while both Cyclin D1 and AQP-5 expression had a significant positive association with unfavorable OS and DFS. The cases of SOC treated with suboptimal surgery revealed a significant association of low Apaf-1, high Cyclin D1, and strong AQPs with the poor response to the first-line chemotherapy (p = 0.047, p < 0.001, and 0.006 respectively). CONCLUSIONS: Down-regulation of Apaf-1 protein and the overexpression of Cyclin D1 and AQP-5 proteins possibly contribute to an aggressive SOC with a high risk of recurrence and poor response to the first-line chemotherapy.