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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2013

01-07-2013 | Gynecologic Oncology

Uterine Leiomyosarcoma Management, Outcome, and Associated Molecular Biomarkers: A Single Institution’s Experience

Authors: Kristelle Lusby, MD, Kari Brewer Savannah, PhD, Elizabeth G. Demicco, MD, PhD, Yiqun Zhang, MS, Markus PH. Ghadimi, MD, Eric D. Young, BS, Chiara Colombo, MD, Ryan Lam, BS, Tugce E. Dogan, MD, Jason L. Hornick, MD, PhD, Alexander J. Lazar, MD, PhD, Kelly K. Hunt, MD, Matthew L. Anderson, MD, PhD, Chad J. Creighton, PhD, Dina Lev, MD, Raphael E. Pollock, MD, PhD

Published in: Annals of Surgical Oncology | Issue 7/2013

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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.
Appendix
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Metadata
Title
Uterine Leiomyosarcoma Management, Outcome, and Associated Molecular Biomarkers: A Single Institution’s Experience
Authors
Kristelle Lusby, MD
Kari Brewer Savannah, PhD
Elizabeth G. Demicco, MD, PhD
Yiqun Zhang, MS
Markus PH. Ghadimi, MD
Eric D. Young, BS
Chiara Colombo, MD
Ryan Lam, BS
Tugce E. Dogan, MD
Jason L. Hornick, MD, PhD
Alexander J. Lazar, MD, PhD
Kelly K. Hunt, MD
Matthew L. Anderson, MD, PhD
Chad J. Creighton, PhD
Dina Lev, MD
Raphael E. Pollock, MD, PhD
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 7/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2834-0

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