Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

Abstract

Apoptosis may occur via a death receptor-dependent or independent (mitochondrial) pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72%) of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (p<0.001). Patients with positive smac/DIABLO tumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up (p=0.043). The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma

“…The process of angiogenesis, in which the interaction of vascular endothelial growth factor (VEGF) and its receptors (VEGFR) plays a key role, is equally important in the progression of the endometrial cancer. These tumors with severe VEGF expression have a worse prognosis than VEGF-negative carcinomas, accordingly, VEGF regarded as an important, clinically relevant inducer of angiogenesis in endometrial adenocarcinoma [12].…”

“…One of the most powerful pro-angiogenic factors, which are involved in the angiogenesis during type 1 endometrial cancer, is vascular endothelial growth factor (VEGF) [12]. The angiogenesis, which progresses in the endometrial cancer, is supposed by the alteration in VEGF/VEGF-receptors signaling pathways [3], the participation of WNT-proteins and β-catenin, but the role of inhibitors and inducers of Wnt-signaling pathway in this process is still unknown [22].…”

Biomarkers as prognostic factors in endometrial cancer.

“…There was a trend towards an association between the strong positive expression of VEGF and 5-year disease-free survival. These results suggest that VEGF may be an important, clinically relevant, inducer of angiogenesis in type I endometrial cancer [33]. Lymphangiogenic factors have recently been studied in endometrial carcinoma, associating aggressive phenotype with the presence of lymphatic vessel infiltration and high lymphatic vessel density [34,35].…”

DIABLO (diablo, IAP-binding mitochondrial protein)

“…Negative expression of Smac is a sign of poor prognostic in this kind of tumor (Dobrzycka et al, 2010).…”