Identification of two molecular groups of seminomas by using expression and tissue microarrays.
Highly effective tailored clinical management of testicular germ cell tumors is based on the identification of two major histologic subtypes: seminomatous and nonseminomatous germ cell tumors. Expression array analysis of these two histologic subtypes using hierarchical clustering reveals two tumor groups, one composed solely of seminomas and the other containing embryonal carcinomas and seminomas. Supervised analysis between these groups identified 55 significantly dysregulated genes (false discovery rate = 2.3). The genes with the highest overexpression in the first group compared with the second included SLC43A1 (POV1), NET-7, IGF2, and JUP; down-regulated genes included GRB7, PFKP, and CDC6. In situ hybridization of SLC43A1 mRNA showed significantly increased signal intensity in the seminomas. At the protein level, expression of the immunohistochemical markers cytokeratins (pan-cytokeratin staining), placental-like alkaline phosphatase, anti-cytokeratin clone 5.2, CD30, anion exchanger 1/3, junction plakoglobulin (JUP), and POU domain, class 5, transcription factor 1 (octomer-binding transcription factor 3/4) was significantly different between seminomas and embryonal tumors. Hierarchical clustering based on a refined protein expression profile identified two groups, the first consisting solely of seminomas the other of seminomas and embryonal carcinomas. No histomorphologic differences were observed between the two seminoma groups such as the presence or absence of lymphocytes or extent of stromal elements. In summary, using independent methodologies and samples, we have identified two groups of seminomas. One group of seminomas has a molecular profile similar to embryonal carcinoma. The findings in the current study may help explain aberrant immunoprofiles seen with some seminomas.
Hofer
Matthias D
MD
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Browne
Tara J
TJ
He
Le
L
Skotheim
Rolf I
RI
Lothe
Ragnhild A
RA
Rubin
Mark A
MA
D027241:Amino Acid Transport System y+L; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics; D016000:Cluster Analysis; D051180:Desmoplakins; D051382:GRB7 Adaptor Protein / Q000032:analysis / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000032:analysis / Q000235:genetics; D018239:Seminoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods*; D051185:gamma Catenin / Q000032:analysis / Q000235:genetics
D027241:Amino Acid Transport System y+L; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D051180:Desmoplakins; C495955:GRB7 protein, human; C035170:IGF2 protein, human; C495292:JUP protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; C115131:SLC43A1 protein, human; D051185:gamma Catenin; D051382:GRB7 Adaptor Protein; D007335:Insulin-Like Growth Factor II