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Heublein, Sabine; Vrekoussis, Thomas; Etzl, Ronny; Rotzoll, Daisy; Kuhn, Christina; Faigle, Gesine; Navrozoglou, Iordanis; Stefos, Theodore; Makrigiannakis, Antonis; Jeschke, Udo (2017): Alpha tocopherol transfer protein (alpha TTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival. In: Journal of Cancer Research and Clinical Oncology, Vol. 143, No. 5: pp. 773-781
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Abstract

Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein alpha TTP facilitates its cellular delivery. We hypothesize that alpha TTP could be present in and have an impact on endometrial cancer. Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. alpha TTP was detected by immunocytochemistry and western blot. alpha I<currency>I<currency>P expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score. AAPH- and BSO-induced alpha TTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that alpha TTP expression correlated with FIGO stage (p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower alpha TTP expression compared to cases with higher expression (p = 0.041). The current results show that alpha TTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating alpha TTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of alpha TTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.