Identification of two molecular groups of seminomas by using expression and tissue microarrays.

TitleIdentification of two molecular groups of seminomas by using expression and tissue microarrays.
Publication TypeJournal Article
Year of Publication2005
AuthorsHofer MD, Browne TJ, He L, Skotheim RI, Lothe RA, Rubin MA
JournalClin Cancer Res
Volume11
Issue16
Pagination5722-9
Date Published2005 Aug 15
ISSN1078-0432
KeywordsAmino Acid Transport System y+L, Cell Cycle Proteins, Cluster Analysis, Desmoplakins, gamma Catenin, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, GRB7 Adaptor Protein, Humans, Immunohistochemistry, In Situ Hybridization, Insulin-Like Growth Factor II, Male, Neoplasm Proteins, Nuclear Proteins, Oligonucleotide Array Sequence Analysis, Proteins, Seminoma, Testicular Neoplasms, Tissue Array Analysis
Abstract

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.

DOI10.1158/1078-0432.CCR-05-0533
Alternate JournalClin. Cancer Res.
PubMed ID16115909
Grant ListCA97063 / CA / NCI NIH HHS / United States