Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.
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Masaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech RepublicMasaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech Republic
Janacova, Lucia
Faktor, Jakub
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Masaryk Mem Canc Inst, Reg Ctr Appl Mol Oncol, Brno 65653, Czech RepublicMasaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech Republic
Faktor, Jakub
Capkova, Lenka
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Masaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech RepublicMasaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech Republic
Capkova, Lenka
Paralova, Vendula
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Masaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech RepublicMasaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech Republic
Paralova, Vendula
Pospisilova, Anna
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Masaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech RepublicMasaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech Republic
Pospisilova, Anna
Podhorec, Jan
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Masaryk Mem Canc Inst, Reg Ctr Appl Mol Oncol, Brno 65653, Czech Republic
Masaryk Mem Canc Inst, Dept Comprehens Canc Care, Brno 65653, Czech RepublicMasaryk Univ, Fac Sci, Dept Biochem, Brno 62500, Czech Republic