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Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma.
- Source :
-
Annals of surgical oncology [Ann Surg Oncol] 2016 Jul; Vol. 23 (7), pp. 2220-8. Date of Electronic Publication: 2016 Feb 03. - Publication Year :
- 2016
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor genetics
Combined Modality Therapy
Female
Follow-Up Studies
Histiocytoma, Malignant Fibrous metabolism
Histiocytoma, Malignant Fibrous pathology
Histiocytoma, Malignant Fibrous therapy
Humans
Immunoenzyme Techniques
Male
MicroRNAs genetics
Middle Aged
Neoplasm Recurrence, Local metabolism
Neoplasm Recurrence, Local pathology
Neoplasm Recurrence, Local therapy
Prognosis
Sarcoma metabolism
Sarcoma pathology
Sarcoma therapy
Soft Tissue Neoplasms metabolism
Soft Tissue Neoplasms pathology
Soft Tissue Neoplasms therapy
Survival Rate
Tissue Array Analysis
Young Adult
Biomarkers, Tumor metabolism
Histiocytoma, Malignant Fibrous mortality
Neoplasm Recurrence, Local mortality
Sarcoma mortality
Soft Tissue Neoplasms mortality
Subjects
Details
- Language :
- English
- ISSN :
- 1534-4681
- Volume :
- 23
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Annals of surgical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 26847678
- Full Text :
- https://doi.org/10.1245/s10434-016-5115-5