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

BMC Cancer. 2020 Aug 5;20(1):728. doi: 10.1186/s12885-020-07220-6.

Abstract

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.

Keywords: Biomarkers; Immunohistochemistry; Relapse; Testicular germ cell tumors; Vascular invasion.

MeSH terms

  • 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 Recurrence, Local* / pathology
  • Neoplasm Staging
  • Neoplasms, Germ Cell and Embryonal / chemistry*
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / pathology
  • RNA-Binding Proteins / analysis
  • Receptors, CXCR4 / analysis
  • Retrospective Studies
  • Seminoma / chemistry*
  • Seminoma / mortality
  • Seminoma / pathology
  • Testicular Neoplasms / chemistry*
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / pathology
  • Tumor Microenvironment
  • beta Catenin / analysis

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Antigens, Surface
  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Chorionic Gonadotropin
  • L-selectin counter-receptors
  • MIB-1 antibody
  • Membrane Proteins
  • RNA-Binding Proteins
  • Receptors, CXCR4
  • Tex19 protein, human
  • beta Catenin

Supplementary concepts

  • Nonseminomatous germ cell tumor
  • Testicular Germ Cell Tumor