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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2364-2372
Number of pages9
JournalAnnals of Surgical Oncology
Volume20
Issue number7
DOIs
Publication statusPublished - Jul 2013

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Leiomyosarcoma
Biomarkers
Neoplasms
Catenins
Metastasectomy
Survival
Paraffin
Formaldehyde
Vascular Endothelial Growth Factor A
Cell Survival
Cell Cycle
Hormones
Neoplasm Metastasis
Recurrence
Lung
Therapeutics

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Lusby, K., Savannah, K. B., Demicco, E. G., Zhang, Y., Ghadimi, M. P., Young, E. D., ... Pollock, R. E. (2013). Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: A single institution's experience. Annals of Surgical Oncology, 20(7), 2364-2372. https://doi.org/10.1245/s10434-012-2834-0

Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers : A single institution's experience. / Lusby, Kristelle; Savannah, Kari Brewer; Demicco, Elizabeth G.; Zhang, Yiqun; Ghadimi, Markus Ph; Young, Eric D.; Colombo, Chiara; Lam, Ryan; Dogan, Tugce E.; Hornick, Jason L.; Lazar, Alexander J.; Hunt, Kelly K.; Anderson, Matthew L.; Creighton, Chad J.; Lev, Dina; Pollock, Raphael E.

In: Annals of Surgical Oncology, Vol. 20, No. 7, 07.2013, p. 2364-2372.

Research output: Contribution to journalArticle

Lusby, K, Savannah, KB, Demicco, EG, Zhang, Y, Ghadimi, MP, Young, ED, Colombo, C, Lam, R, Dogan, TE, Hornick, JL, Lazar, AJ, Hunt, KK, Anderson, ML, Creighton, CJ, Lev, D & Pollock, RE 2013, 'Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: A single institution's experience', Annals of Surgical Oncology, vol. 20, no. 7, pp. 2364-2372. https://doi.org/10.1245/s10434-012-2834-0
Lusby, Kristelle ; Savannah, Kari Brewer ; Demicco, Elizabeth G. ; Zhang, Yiqun ; Ghadimi, Markus Ph ; Young, Eric D. ; Colombo, Chiara ; Lam, Ryan ; Dogan, Tugce E. ; Hornick, Jason L. ; Lazar, Alexander J. ; Hunt, Kelly K. ; Anderson, Matthew L. ; Creighton, Chad J. ; Lev, Dina ; Pollock, Raphael E. / Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers : A single institution's experience. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 7. pp. 2364-2372.
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T1 - Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers

T2 - A single institution's experience

AU - Lusby, Kristelle

AU - Savannah, Kari Brewer

AU - Demicco, Elizabeth G.

AU - Zhang, Yiqun

AU - Ghadimi, Markus Ph

AU - Young, Eric D.

AU - Colombo, Chiara

AU - Lam, Ryan

AU - Dogan, Tugce E.

AU - Hornick, Jason L.

AU - Lazar, Alexander J.

AU - Hunt, Kelly K.

AU - Anderson, Matthew L.

AU - Creighton, Chad J.

AU - Lev, Dina

AU - Pollock, Raphael E.

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

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