title: Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors.
abstract: BACKGROUND
  Testicular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes.
  
  
  METHODS
  Immunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software.
  
  
  RESULTS
  In tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis.
  
  
  CONCLUSIONS
  In conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15 expression in the preinvasive precursor cells, which may provide diagnostic value to distinguish between benign and pre-malignant testicular specimen, and may indicate a role for MED15 in carcinogenesis in TGCT.
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Klümper
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Syring
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Offermann
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Adler
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Department of Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.affiliation: Department of Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Department of Urology, University Medical Center, University of Göttingen, Göttingen, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Strauß
authors.affiliation: Institute of Pathology, University Hospital of Göttingen, Robert Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Heinz Joachim
authors.initials: HJ
authors.lastname: Radzun
authors.affiliation: Institute of Pathology, University Hospital of Göttingen, Robert Koch Str. 40, 37075, Göttingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Section for Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: Institute of Pathology, University Hospital of Göttingen, Robert Koch Str. 40, 37075, Göttingen, Germany. felix.bremmer@med.uni-goettingen.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Bremmer
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D056892:Mediator Complex / Q000032:analysis / Q000096:biosynthesis*; D009373:Neoplasms, Germ Cell and Embryonal / Q000145:classification / Q000473:pathology*; D013736:Testicular Neoplasms / Q000145:classification / Q000473:pathology*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C416944:MED15 protein, human; D056892:Mediator Complex