Defining a New Prognostic index for Stage I Non-seminomatous Germ Cell Tumors using CXCL12 Expression and Proportion of Embyronal Carcinoma

2.50
Hdl Handle:
http://hdl.handle.net/11287/593967
Title:
Defining a New Prognostic index for Stage I Non-seminomatous Germ Cell Tumors using CXCL12 Expression and Proportion of Embyronal Carcinoma
Authors:
Gilbert, D. C.; Al-Saadi, R.; Thway, K.; Chandler, Ian; Berney, D. M.; Gabe, R.; Stenning, S.; Sweet, J.; Huddart, R.; Shipley, J. M.
Abstract:
PURPOSE: Up to 50% of patients diagnosed with stage I non-seminomatous germ cell tumors (NSGCT) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up-front. Late toxicities from chemotherapy are increasingly recognised. Based on a potential biological role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse. EXPERIMENTAL DESIGN: Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma) and MIB1 staining for proliferationin formalin fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCT. RESULTS: TE08/TE22 trial patients had a 76.4% 2-year relapse free rate (RFR) and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test p=0.006 for both).There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma and VI defines 3 prognostic groups that were independantly validated. CONCLUSIONS: CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy.
Citation:
Clin Cancer Res. 2016 Mar 1;22(5):1265-73
Publisher:
Clinical Cancer Research
Journal:
Clinical cancer research : an official journal of the American Association for Cancer Research
Issue Date:
9-Oct-2015
URI:
http://hdl.handle.net/11287/593967
DOI:
10.1158/1078-0432.CCR-15-1186
PubMed ID:
26453693
Additional Links:
http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=26453693
Type:
Journal Article
Language:
Eng
ISSN:
1078-0432
Appears in Collections:
2015 RD&E publications; Exeter Clinical Laboratory International (Blood Sciences, Genetics, Cellular Pathology & Microbiology)

Full metadata record

DC FieldValue Language
dc.contributor.authorGilbert, D. C.en
dc.contributor.authorAl-Saadi, R.en
dc.contributor.authorThway, K.en
dc.contributor.authorChandler, Ianen
dc.contributor.authorBerney, D. M.en
dc.contributor.authorGabe, R.en
dc.contributor.authorStenning, S.en
dc.contributor.authorSweet, J.en
dc.contributor.authorHuddart, R.en
dc.contributor.authorShipley, J. M.en
dc.date.accessioned2016-01-19T12:38:04Zen
dc.date.available2016-01-19T12:38:04Zen
dc.date.issued2015-10-09en
dc.identifier.citationClin Cancer Res. 2016 Mar 1;22(5):1265-73en
dc.identifier.issn1078-0432en
dc.identifier.pmid26453693en
dc.identifier.doi10.1158/1078-0432.CCR-15-1186en
dc.identifier.urihttp://hdl.handle.net/11287/593967en
dc.description.abstractPURPOSE: Up to 50% of patients diagnosed with stage I non-seminomatous germ cell tumors (NSGCT) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up-front. Late toxicities from chemotherapy are increasingly recognised. Based on a potential biological role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse. EXPERIMENTAL DESIGN: Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma) and MIB1 staining for proliferationin formalin fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCT. RESULTS: TE08/TE22 trial patients had a 76.4% 2-year relapse free rate (RFR) and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test p=0.006 for both).There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma and VI defines 3 prognostic groups that were independantly validated. CONCLUSIONS: CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy.en
dc.language.isoEngen
dc.publisherClinical Cancer Researchen
dc.relation.urlhttp://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=26453693en
dc.titleDefining a New Prognostic index for Stage I Non-seminomatous Germ Cell Tumors using CXCL12 Expression and Proportion of Embyronal Carcinomaen
dc.typeJournal Articleen
dc.identifier.journalClinical cancer research : an official journal of the American Association for Cancer Researchen

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