DNA fragmentation factors 40 and 45 (DFF40/DFF45) and B-cell lymphoma 2 (Bcl-2) protein are underexpressed in uterine leiomyosarcomas and may predict survival

Abstract

Objectives: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) are responsible for final DNA-laddering during apoptosis, whereas Bcl-2 (B-cell lymphoma 2) is an apoptosis inhibitor. Our aim was to investigate the expression of DFF40, DFF45, and Bcl-2 in uterine leiomyosarcomas (uLMS), leiomyomas (uLM), and the normal myometrium. Furthermore, the correlation between DFF40, DFF45, and Bcl-2 expression and clinicopathological parameters in leiomyosarcomas was assessed. Their prognostic value in disease-free survival (DFS) and overall survival (OS) was also calculated. Materials and methods: This study included 53 cases of uLMS from patients matched for age and menopausal status with 53 cases of uLM and 53 controls of normal myometrium (uM). Case samples of uterine myometrium from leiomyosarcomas (uLMS-M) and leiomyomas (uLM-M) were also studied. Immunohistochemical scoring was undertaken for DFF40, DFF45, and Bcl-2. Results: DFF40, DFF45, and Bcl-2 were significantly underexpressed in uLMS compared with uLMS-M and uM. In uLMS samples, no correlation between the analyzed proteins was observed. Negative DFF40 and Bcl-2, but not DFF45, staining was a predictor of poorer DFS and OS in women with uLMS. uLM showed DFF40 and Bcl-2 overexpression compared with uM and uLM-M, with a significant positive correlation between DFF40 and DFF45. No differences in DFF40, DFF45, and Bcl-2 expression were observed between the uLMS-M, uLM-M, and uM samples, with a significant positive correlation between DFF40 and DFF45 expression. Conclusion: DFF40, DFF45, and Bcl-2 are significantly underexpressed in uLMS, but only a lack of DFF40 and Bcl-2 negatively influences DFS and OS. Disruption of DFF40 and DFF45 expression was observed in uLMS, but not in uLM or control and case myometrium; this may play a role in tumor pathogenesis.