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

Abstract

BackgroundInguinal 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.MethodsFifty-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.ResultsClassical 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.ConclusionsEpididymis 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 materialThe online version of this article (doi:10.1186/s12967-017-1162-3) contains supplementary material, which is available to authorized users.

Testiküler Germ Hücreli Tümörlerin Prognostik Parametrelerine Olgularımız Eşliğinde Güncel Yaklaşım

“…Martinelli et al (25) found that CALCA and MGMT were associated with poor prognosis, and CALCA methylation was associated with refractory disease in germ cell tumors. While microsatellite analysis of mismatch repair genes is not associated with clinical course, epididymal invasion and EGFR expression are associated with recurrence in stage 1 tumors (26). Aurora-B, serine-threonine kinases, GPR30 and HMGAs are the new molecules that can be used in targeted therapy in resistant cases (27).…”

Potential biomarkers for testicular germ cell tumour: Risk assessment, diagnostic, prognostic and monitoring of recurrence

“…Analysis of hMLH1, hMSH2 and EGFR expression in clinical stage I testicular germ cell tumours (CS I TGCT) patients by IHC showed that EGFR was overexpressed in 30% of cases. EGFR expression was associated with higher risk of relapse, which makes it as a new potential prognostic factor of recurrence for CS I TGCT (Sanmamed et al., 2017).…”