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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Translational Medicine 1/2017

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

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2017
Autoren:
Miguel F. Sanmamed, E. Esteban, E. Uriol, R. Zarate, M. Capelan, C. Muriel, G. Crespo, J. P. Berros, P. Pardo-Coto, Q. Perez, C. Alvarez-Fernández, P. Jiménez Fonseca, M. Luque, A. Astudillo
Wichtige Hinweise

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.

Abstract

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.
Zusatzmaterial
Additional file 1: Table S1. Characteristics of primers used in EGFR exons 19, 20 and 21 amplification.
Additional file 2: Table S2. EGFR, hMLH1 and hMSH2 expression in TGCT subtypes.
Additional file 3: Table S3. Univariate analysis Seminomas B. Univariate analysis Non Seminomas.
Additional file 4: Figure S1. Methylation levels result of hMLH1 promoter. Comparison between Tumour (T) and Normal adjacent tissue (N) in 5 patients. Tumors from patients 4, 27 and 43 showed absent expression levels by IHC and tumors from patients 61 and 64 showed low expression levels by IHC. Methylation percentage values are depicted for both average and individual CpG islands of hMLH-1 promoter indicated as CpG1, CpG2, CpG3, CpG4 and CpG5.
Literatur
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