TY - JOUR
T1 - Prediction of relapse in stage I testicular germ cell tumor patients on surveillance
T2 - investigation of biomarkers
AU - Lobo, João
AU - Gillis, Ad J M
AU - van den Berg, Annette
AU - Looijenga, Leendert H J
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/8/5
Y1 - 2020/8/5
N2 - 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.
AB - 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.
KW - Adult
KW - Antibodies, Antinuclear/analysis
KW - Antibodies, Monoclonal/analysis
KW - Antigens, Surface/analysis
KW - Biomarkers, Tumor/analysis
KW - Chemokine CXCL12/analysis
KW - Chorionic Gonadotropin/blood
KW - Confidence Intervals
KW - Disease-Free Survival
KW - Humans
KW - Male
KW - Membrane Proteins/analysis
KW - Neoplasm Invasiveness
KW - Neoplasm Recurrence, Local/mortality
KW - Neoplasm Staging
KW - Neoplasms, Germ Cell and Embryonal/chemistry
KW - RNA-Binding Proteins/analysis
KW - Receptors, CXCR4/analysis
KW - Retrospective Studies
KW - Seminoma/chemistry
KW - Testicular Neoplasms/chemistry
KW - Tumor Microenvironment
KW - beta Catenin/analysis
UR - http://www.scopus.com/inward/record.url?scp=85089171444&partnerID=8YFLogxK
U2 - 10.1186/s12885-020-07220-6
DO - 10.1186/s12885-020-07220-6
M3 - Article
C2 - 32758242
SN - 1471-2407
VL - 20
SP - 728
JO - BMC Cancer
JF - BMC Cancer
IS - 1
ER -