title: Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer.
abstract: 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.
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway ; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Henrica M J
authors.initials: HM
authors.lastname: Werner
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway ; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Jone
authors.initials: J
authors.lastname: Trovik
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway.
authors.forename: Mari K
authors.initials: MK
authors.lastname: Halle
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway ; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wik
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Medicine, The University of Bergen, Bergen, Norway ; Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway.
authors.forename: Even
authors.initials: E
authors.lastname: Birkeland
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Bredholt
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway ; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ingvild L
authors.initials: IL
authors.lastname: Tangen
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
authors.affiliation: Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway ; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D050777:Stathmin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D050777:Stathmin; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel