Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation.
<italic>Background.</italic> Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. <italic>Methods</italic>. Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospectiv...
| Publicado en: | Sarcoma pp. 1 - 11 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
2/28/2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=128231422&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 128231422 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 1357714X 57R jtl: Sarcoma issn: 1357714X maglogo: Y pubinfo: dt: 2/28/2018 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 128231422 128231422 128231422 10.1155/2018/8310950 128231422 ppf: 1 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation. aug: au: Kane, John M. Magliocco, Anthony Zhang, Qiang Wang, Dian Klimowicz, Alex Harris, Jonathan Simko, Jeff DeLaney, Thomas Kraybill, William Kirsch, David G. affil: Roswell Park Cancer Institute, Buffalo, NY, USA sug: subj: Soft Tissue Neoplasms Therapy Sarcoma Therapy Biological Markers Neoadjuvant Therapy Chemoradiotherapy, Adjuvant Gene Expression Soft Tissue Neoplasms Prognosis Sarcoma Prognosis Treatment Outcomes Human Odds Ratio Survival Tissue Array Analysis Cancer Patients Carbonic Anhydrases Membrane Transport Proteins Transferases Genes, Tumor Suppressor DNA-Binding Proteins Transcription Factors Signal Transduction DNA ab: <italic>Background.</italic> Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. <italic>Methods</italic>. Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). <italic>Results</italic>. Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p=0.017; HR 4.16, p=0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS. <italic>Conclusions</italic>. PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1<italic>α</italic> signaling, and a p53 nuclear accumulation DNA damage response. <italic>Clinical Trial Registration</italic>. NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is <ext-link>NCT00002791</ext-link>. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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