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Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours

BACKGROUND: Inguinal orchiectomy is curative in 70–80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite in...

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Autores principales: Sanmamed, Miguel F., Esteban, E., Uriol, E., Zarate, R., Capelan, M., Muriel, C., Crespo, G., Berros, J. P., Pardo-Coto, P., Perez, Q., Alvarez-Fernández, C., Jiménez Fonseca, P., Luque, M., Astudillo, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358043/
https://www.ncbi.nlm.nih.gov/pubmed/28320414
http://dx.doi.org/10.1186/s12967-017-1162-3
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author Sanmamed, Miguel F.
Esteban, E.
Uriol, E.
Zarate, R.
Capelan, M.
Muriel, C.
Crespo, G.
Berros, J. P.
Pardo-Coto, P.
Perez, Q.
Alvarez-Fernández, C.
Jiménez Fonseca, P.
Luque, M.
Astudillo, A.
author_facet Sanmamed, Miguel F.
Esteban, E.
Uriol, E.
Zarate, R.
Capelan, M.
Muriel, C.
Crespo, G.
Berros, J. P.
Pardo-Coto, P.
Perez, Q.
Alvarez-Fernández, C.
Jiménez Fonseca, P.
Luque, M.
Astudillo, A.
author_sort Sanmamed, Miguel F.
collection PubMed
description BACKGROUND: Inguinal orchiectomy is curative in 70–80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays. RESULTS: Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3–9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations. CONCLUSIONS: Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1162-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-53580432017-03-20 Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours Sanmamed, Miguel F. Esteban, E. Uriol, E. Zarate, R. Capelan, M. Muriel, C. Crespo, G. Berros, J. P. Pardo-Coto, P. Perez, Q. Alvarez-Fernández, C. Jiménez Fonseca, P. Luque, M. Astudillo, A. J Transl Med Research BACKGROUND: Inguinal orchiectomy is curative in 70–80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays. RESULTS: Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3–9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations. CONCLUSIONS: Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1162-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-20 /pmc/articles/PMC5358043/ /pubmed/28320414 http://dx.doi.org/10.1186/s12967-017-1162-3 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sanmamed, Miguel F.
Esteban, E.
Uriol, E.
Zarate, R.
Capelan, M.
Muriel, C.
Crespo, G.
Berros, J. P.
Pardo-Coto, P.
Perez, Q.
Alvarez-Fernández, C.
Jiménez Fonseca, P.
Luque, M.
Astudillo, A.
Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours
title Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours
title_full Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours
title_fullStr Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours
title_full_unstemmed Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours
title_short Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours
title_sort epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage i testicular germ cell tumours
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358043/
https://www.ncbi.nlm.nih.gov/pubmed/28320414
http://dx.doi.org/10.1186/s12967-017-1162-3
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