Defining a New Prognostic Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12 Expression and Proportion of Embryonal Carcinoma.
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Date
2016-03-01Author
Gilbert, DC
Al-Saadi, R
Thway, K
Chandler, I
Berney, D
Gabe, R
Stenning, SP
Sweet, J
Huddart, R
Shipley, JM
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late toxicities from chemotherapy are increasingly recognized. Based on a potential biologic 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 proliferation in formalin-fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCTs. RESULTS: TE08/TE22 trial patients had a 76.4% 2-year relapse-free rate, 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 three prognostic groups that were independently 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.
Subject
Humans
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Neoplasm Staging
Disease-Free Survival
Risk Factors
Gene Expression Regulation, Neoplastic
Male
Chemokine CXCL12
Biomarkers, Tumor
Research team
Sarcoma Molecular Pathology
Clinical Academic Radiotherapy (Huddart)
Language
eng
Date accepted
2015-09-18
License start date
2016-03
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2016, 22 (5), pp. 1265 - 1273
Publisher
AMER ASSOC CANCER RESEARCH
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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