Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: A single institution's experience

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.