title: Defining a New Prognostic Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12 Expression and Proportion of Embryonal Carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom. MRC Clinical Trials Unit, Aviation House, London, United Kingdom.
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Gilbert
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Saadi
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Khin
authors.initials: K
authors.lastname: Thway
authors.affiliation: Department of Histopathology, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Chandler
authors.affiliation: Barts Cancer Institute, Queen Mary, University of London, St Bartholomew's Hospital, London, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Berney
authors.affiliation: The Hull York Medical School, University of York, Heslington, York, United Kingdom.
authors.forename: Rhian
authors.initials: R
authors.lastname: Gabe
authors.affiliation: MRC Clinical Trials Unit, Aviation House, London, United Kingdom.
authors.forename: Sally P
authors.initials: SP
authors.lastname: Stenning
authors.affiliation: Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Joan
authors.initials: J
authors.lastname: Sweet
authors.affiliation: Department of Academic Radiotherapy and Oncology, Royal Marsden Hospitals NHS Foundation Trust, Sutton, Surrey, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom. janet.shipley@icr.ac.uk.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Shipley
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D054377:Chemokine CXCL12 / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000145:classification / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12