title: Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: a single institution's experience.
abstract: BACKGROUND
  Uterine leiomyosarcoma (ULMS) is an aggressive, rapidly progressive tumor lacking clinical and molecular predictors of outcome.
  
  
  METHODS
  ULMS patients (n = 349) were classified by disease status at presentation to MDACC as having intra-abdominal (n = 157) or distant metastatic disease (n = 192). Patient, tumor, treatment, and outcome variables were retrospectively retrieved. Formalin-fixed, paraffin-embedded tumor and control tissues from these patients (n = 109) were assembled in a tissue microarray and evaluated for hormone receptors and markers of angiogenesis, cell-cycle progression and survival. Patient, tumor, and treatment variables were correlatively analyzed.
  
  
  RESULTS
  The 5- and 10-year disease-specific survival (DSS) for the cohort was 42 and 27 %, respectively. Patients with primary intra-abdominal tumors had better outcomes than those with recurrent intraperitoneal tumors. Whites had a more favorable prognosis. In patients with intra-abdominal tumors, only mitotic count >10M/10HPF portended poorer prognosis. Patients with pulmonary metastasis had improved outcomes with "curative" metastasectomy. ULMS samples exhibited loss of ER and PR expression, overexpressed Ki-67, and altered p53, Rb, p16, cytoplasmic β-catenin, EGFR, PDGFR-α, PDGFR-β, and AXL levels. Metastatic tumors had increased VEGF, Ki-67, and survivin expression versus localized disease. Survivin and β-catenin expression were associated with intraperitoneal recurrence; high bcl-2 expression predicted longer DSS.
  
  
  CONCLUSIONS
  Analysis of both clinicopathologic factors and immunohistochemical biomarkers in ULMS identified several prognostic clinical and molecular factors, suggesting that further study may lead to improved ULMS understanding and treatment.
authors: Department of Surgical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors: Kristelle
authors: K
authors: Lusby
authors: Kari Brewer
authors: KB
authors: Savannah
authors: Elizabeth G
authors: EG
authors: Demicco
authors: Yiqun
authors: Y
authors: Zhang
authors: Markus Ph
authors: MP
authors: Ghadimi
authors: Eric D
authors: ED
authors: Young
authors: Chiara
authors: C
authors: Colombo
authors: Ryan
authors: R
authors: Lam
authors: Tugce E
authors: TE
authors: Dogan
authors: Jason L
authors: JL
authors: Hornick
authors: Alexander J
authors: AJ
authors: Lazar
authors: Kelly K
authors: KK
authors: Hunt
authors: Matthew L
authors: ML
authors: Anderson
authors: Chad J
authors: CJ
authors: Creighton
authors: Dina
authors: D
authors: Lev
authors: Raphael E
authors: RE
authors: Pollock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000556:secondary*; D008875:Middle Aged; D008940:Mitotic Index; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015996:Survival Rate; D000077022:Survivin; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016160:Retinoblastoma Protein; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D020794:Receptor Protein-Tyrosine Kinases