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Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes.

Methods

A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome.

Results

At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R.

Discussion

Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.

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Acknowledgment

Funding for this research was provided in part by a NIH/NCI K08CA160443 (to KET), the Sally M. Kingsbury Sarcoma Research Foundation (to KET), the Jay Vernon Jackson Fund (to KET), Michael and Mary Kay Poulos (to KET), the Marty Lindley Foundation (supporting KLW and DRI), and the Amschwand Sarcoma Cancer Foundation (supporting CDM). None of the funding organizations had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Disclosures

We have no conflicts of interest to declare. Data in this report were presented previously as an oral presentation at the SSO 2015 Annual Cancer Symposium, Houston, TX, on March 26, 2015.

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Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Christina L. Roland MD, Caitlin D. May PhD, Kelsey L. Watson BS, Sean P. Dineen MD, Rachel Feig BS, Sharon Landers PhD, Barry Feig MD, Kelly K. Hunt MD, Janice N. Cormier MD & Keila E. Torres MD, PhD

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ghadah A. Al Sannaa MD, Davis R. Ingram BS, Wei-Lien Wang MD & Alexander J. Lazar MD, PhD

  3. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    B. Ashleigh Guadagnolo MD

  4. The University of Texas Health Science Center at Houston – Graduate School of Biomedical Sciences, Houston, TX, USA

    Caitlin D. May PhD

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  1. Christina L. Roland MD
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Corresponding author

Correspondence to Keila E. Torres MD, PhD.

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Roland, C.L., May, C.D., Watson, K.L. et al. Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma. Ann Surg Oncol 23, 2220–2228 (2016). https://doi.org/10.1245/s10434-016-5115-5

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  • DOI: https://doi.org/10.1245/s10434-016-5115-5

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