Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers

João Lobo, Ad J M Gillis, Annette van den Berg, Leendert H J Looijenga

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


BACKGROUND: Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables. We aimed to assess the prognostic value of previously suggested biomarkers, related to proliferation (MIB-1 and TEX19) and to immune microenvironment (CXCL12, CXCR4, beta-catenin and MECA-79) in a surveillance cohort of stage I testicular germ cell tumor patients.

METHODS: A total of 70 patients were included. Survival analyses were performed, including Cox regression models.

RESULTS: Patients with vascular invasion and elevated human chorionic gonadotropin levels showed significantly poorer relapse-free survival in multivariable analysis (hazard ratio = 2.820, 95% confidence interval 1.257-6.328; hazard ratio = 3.025, 95% confidence interval 1.345-6.808). Patients with no vascular invasion but with MIB-1 staining in > 50% tumor cells showed significantly shorter relapse-free survival (p = 0.042). TEX19 nuclear immunoexpression was confirmed in spermatogonial cells, and weak cytoplasmic immunoexpression was depicted in 15/70 tumors, not significantly impacting survival. CXCL12 immunoexpression in tumor cells did not associate with relapse, but non-seminoma patients exhibiting vascular invasion and CXCL12-positive stromal/inflammatory cells showed significantly improved relapse-free survival (p = 0.015). Exclusively nuclear immunoexpression of CXCR4 associated with better relapse-free survival (p = 0.032), but not after adjusting for vascular invasion. Patients with higher beta-catenin scores showed a tendency for poorer relapse-free survival (p = 0.056). MECA-79 immunoexpression was absent.

CONCLUSIONS: The informative protein biomarkers (i.e., MIB-1, CXCL12, beta-catenin, and possibly CXCR4) may prove useful for risk-stratifying patients if validated in larger, multicentric and well-defined studies. Currently, classical histopathological features of testicular germ cell tumors remain key for relapse prediction.

Original languageEnglish
Pages (from-to)728
JournalBMC Cancer
Issue number1
Publication statusPublished - 5 Aug 2020
Externally publishedYes


  • Adult
  • Antibodies, Antinuclear/analysis
  • Antibodies, Monoclonal/analysis
  • Antigens, Surface/analysis
  • Biomarkers, Tumor/analysis
  • Chemokine CXCL12/analysis
  • Chorionic Gonadotropin/blood
  • Confidence Intervals
  • Disease-Free Survival
  • Humans
  • Male
  • Membrane Proteins/analysis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local/mortality
  • Neoplasm Staging
  • Neoplasms, Germ Cell and Embryonal/chemistry
  • RNA-Binding Proteins/analysis
  • Receptors, CXCR4/analysis
  • Retrospective Studies
  • Seminoma/chemistry
  • Testicular Neoplasms/chemistry
  • Tumor Microenvironment
  • beta Catenin/analysis


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