title: Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Christina L
authors: CL
authors: Roland
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|The University of Texas Health Science Center at Houston - Graduate School of Biomedical Sciences, Houston, TX, USA.
authors: Caitlin D
authors: CD
authors: May
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Kelsey L
authors: KL
authors: Watson
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Ghadah A
authors: GA
authors: Al Sannaa
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Sean P
authors: SP
authors: Dineen
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Rachel
authors: R
authors: Feig
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Sharon
authors: S
authors: Landers
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Davis R
authors: DR
authors: Ingram
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Wei-Lien
authors: WL
authors: Wang
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: B Ashleigh
authors: BA
authors: Guadagnolo
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Barry
authors: B
authors: Feig
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Kelly K
authors: KK
authors: Hunt
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Janice N
authors: JN
authors: Cormier
authors: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Alexander J
authors: AJ
authors: Lazar
authors: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ketorres@mdanderson.org.
authors: Keila E
authors: KE
authors: Torres
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D051677:Histiocytoma, Malignant Fibrous / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012509:Sarcoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs