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

Duncan C Gilbert, Reem Al-Saadi, Khin Thway, Ian Chandler, Daniel M Berney, Rhian Gabe, Sally Stenning, Joan Sweet, Robert Huddart, Janet M Shipley

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1-34
Number of pages34
JournalClinical Cancer Research
Publication statusPublished - 1 Nov 2015

Bibliographical note

Copyright © 2015, American Association for Cancer Research.

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