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

doi:10.1186/s12885-020-07220-6

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 journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Pages (from-to)	728
Journal	BMC Cancer
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12885-020-07220-6
Publication status	Published - 5 Aug 2020
Externally published	Yes

Keywords

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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10.1186/s12885-020-07220-6

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@article{5108b96b978e49e1bc1ffa0b2607bde9,

title = "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.",

keywords = "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",

author = "Jo{\~a}o Lobo and Gillis, {Ad J M} and {van den Berg}, Annette and Looijenga, {Leendert H J}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = aug,

day = "5",

doi = "10.1186/s12885-020-07220-6",

language = "English",

volume = "20",

pages = "728",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "BioMed Central Ltd.",

number = "1",

}

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

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 -

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

Abstract

Keywords

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