Abstract
BackgroundBetter 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.MethodsA total of 70 patients were included. Survival analyses were performed, including Cox regression models.ResultsPatients 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.ConclusionsThe 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.
Highlights
Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables
In this work we aim to assess the prognostic value of biomarkers related to proliferation (MIB-1, TEX19) and to the surrounding immune microenvironment (CXCL12, CXCR4, beta-catenin and MECA-79) in a cohort of stage I testicular germ cell tumor patients undergoing surveillance, including their impact in patient outcome, and to compare their performance to the classical histopathological variable vascular invasion
There were four late relapses, all corresponding to seminoma patients with recurrence of disease in retroperitoneal lymph-nodes, and one died of disease
Summary
Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables. Still a subgroup of these patients relapses, most frequently during the first 2 years after initial diagnosis, and requires further treatments, which possibly lead to morbidity and mortality [7, 8] For this reason, there is an urgent need for predictive biomarkers to assess the risk of stage I patients, and accurately discriminate those truly benefiting from adjuvant treatment to prevent relapses, from those that can safely be followed using surveillance to avoid early and late side effects of additional treatments on individuals most likely becoming longterm cancer survivors [9,10,11]. Accurate pathological assessment is key since overdiagnosis (commonly observed in vascular invasion assessment by less experienced centers) may result in overtreatment [17, 18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
