title: Survivin and XIAP: two valuable biomarkers in medullary thyroid carcinoma.
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) accounts for ∼5% of all thyroid malignancies. To date, surgery is the first-line therapy with curative intention. However, for advanced MTC, conventional chemotherapeutic agents do not provide convincing results. Therefore, the identification of biomarkers that can be antagonised by small-molecule therapeutics may lead to novel encouraging treatment options.
  
  
  METHODS
  Seventy-nine patients with surgically resected and histologically confirmed MTC were included in this study. Tissue microarrays were constructed to assess the relationship between inhibitor of apoptosis proteins (IAPs) survivin or XIAP expression levels and clinicopathological variables as well as overall survival.
  
  
  RESULTS
  High survivin or XIAP expression was associated with an advanced T-stage and metastatic disease. Whereas tissue expression levels of survivin correlated with serum calcitonin levels, XIAP was overexpressed in the subgroup of patients with sporadic MTC. Both IAPs were negatively associated with patient survival in the multivariate Cox regressions analysis (survivin: hazard ratio (HR) 1.62; 95% confidence interval (CI): 1.21-2.16; P=0.001; XIAP: HR 1.78; 95% CI: 1.16-2.72; P=0.008).
  
  
  CONCLUSIONS
  Survivin and XIAP demonstrate distinct expression patterns in MTCs, which are associated with advanced disease and poor prognosis. We thus provide first evidence that both IAPs might serve as viable targets in patients with MTC.
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Werner
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Tamkan-Ölcek
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.
authors.forename: Levent
authors.initials: L
authors.lastname: Dizdar
authors.affiliation: Institute of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany.
authors.forename: Jasmin C
authors.initials: JC
authors.lastname: Riemer
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.|Department of Surgery I, Ingolstadt Medical Center, Ingolstadt, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.|Department of Surgery, Marien-Hospital Euskirchen, Euskirchen, Germany.
authors.forename: Kenko
authors.initials: K
authors.lastname: Cupisti
authors.affiliation: Coordination Center for Clinical Trials, Heinrich-Heine-University and University Hospital Duesseldorf, Duesseldorf, Germany.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Verde
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.
authors.forename: Wolfram T
authors.initials: WT
authors.lastname: Knoefel
authors.affiliation: Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Building 12.46, Moorenstrasse 5, Duesseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Krieg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D000077022:Survivin; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*; D055815:Young Adult
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human