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

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.

Promoter methylation of DNA homologous recombination genes is predictive of the responsiveness to PARP inhibitor treatment in testicular germ cell tumors

“…Consequently, increased incidence of side effects has been observed (secondary neoplasms, metabolic syndrome, coronary heart disease and others) in those young patients [3]. Thus, there is a need for biomarkers that reliably stratify patients concerning the risk of relapse [4]. Additionally, there is an urgent need for novel and less toxic targeted treatment options that might allow for dose reduction of chemotherapy agents.…”

Targeting of Deregulated Wnt/β-Catenin Signaling by PRI-724 and LGK974 Inhibitors in Germ Cell Tumor Cell Lines

“…Another work has shown that high β-catenin expression in primary testicular GCTs was associated with relapse and NS-GCT histology in clinical stage I disease. This finding may help refining the approach to risk stratification of stage I GCTs [ 73 ]. Western blot analysis in our GCT cell lines revealed significantly increased levels of β-catenin protein expression in two cisplatin-resistant cell lines with the exception of NTERA-2 CisR cells where the expression was significantly decreased.…”

Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm

“…The latter comprise a complex array of subtypes that include embryonal carcinoma (EC), choriocarcinoma (CH), yolk sac tumor (YST), and teratoma (TE) [1][2][3][4][5][6][7]. Overall, TGCTs represent a model of curable disease, with most patients presenting with stage I disease (around 70%), but approximately 75% of these are cured with orchiectomy alone, without the need for subsequent adjuvant treatments [4,8,9]. For those who require systemic therapy, TGCTs present extreme sensitivity to cisplatin-based chemotherapy, due to their unique molecular background [3,10].…”

“…For those who require systemic therapy, TGCTs present extreme sensitivity to cisplatin-based chemotherapy, due to their unique molecular background [3,10]. However, a significant group of patients relapse, most frequently within the first two years after initial diagnosis [9,11]. Thus, inguinal orchiectomy followed by close surveillance may not be enough, implying the need for further treatments, which leads to higher morbidity [9].…”

“…However, a significant group of patients relapse, most frequently within the first two years after initial diagnosis [9,11]. Thus, inguinal orchiectomy followed by close surveillance may not be enough, implying the need for further treatments, which leads to higher morbidity [9].…”