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



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.



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.



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.
Department of Immunobiology, School of Medicine, Yale University, 300 George Street, Suite 203A, New Haven, CT, 06511, USA. miguel.sanmamed@yale.edu.|Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain. miguel.sanmamed@yale.edu.
Miguel F
0000-0002-7295-6074
MF
Sanmamed
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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E
Esteban
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
E
E
Uriol
Clinical Genetics Unit, Clínica Universidad de Navarra, Pamplona, Spain.
R
R
Zarate
Breast Unit, Royal Marsden NHS Foundation Trust, London, UK.
M
M
Capelan
Department of Medical Oncology, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
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C
Muriel
Department of Medical Oncology, Hospital Universitario de Burgos, Burgos, Spain.
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G
Crespo
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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JP
Berros
Department of Medical Oncology, Centro Médico de Asturias, Oviedo, Spain.
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P
Pardo-Coto
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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Q
Perez
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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C
Alvarez-Fernández
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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P
Jiménez Fonseca
Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain.
M
M
Luque
Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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A
Astudillo
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics; D003710:Demography; D018572:Disease-Free Survival; D004822:Epididymis / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
EGFR; Epididymis invasion; MSI; Testicular germ cell tumour; hMLH-1; hMSH-2