TY - JOUR
T1 - The Y-encoded TSPY protein
T2 - a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors
AU - Li, Yunmin
AU - Tabatabai, Z Laura
AU - Lee, Tin-Lap
AU - Hatakeyama, Shingo
AU - Ohyama, Chikara
AU - Chan, Wai-Yee
AU - Looijenga, Leendert H J
AU - Lau, Yun-Fai Chris
N1 - Funding Information:
This research was partially supported by grants from the VA Medical Research Service and Department of Defense Prostate Cancer Research Program to Y-FCL.
PY - 2007/10
Y1 - 2007/10
N2 - The testis-specific protein Y-encoded (TSPY) gene is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY) that predisposes dysgenetic gonads of intersex patients to gonadoblastoma development. TSPY is expressed at high levels in gonadoblastoma tissues, supporting its possible oncogenic function in this type of germ cell tumors. To explore the possibility that this Y chromosome gene is also involved in pathogenesis of the more common testicular germ cell tumors (TGCTs), we have conducted various expression studies using immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction analysis on 171 cases of TGCTs and selected normal testis controls. Our results demonstrated that TSPY protein is abundantly expressed in the precursor, carcinoma in situ or intratubular germ cell neoplasia unclassified, and seminoma, but only minimally or not expressed in various types of nonseminomas. TSPY coexpresses with established germ cell tumor markers (such as placental-like alkaline phosphatase, c-KIT, OCT4) and proliferative markers (such as Ki-67 and cyclin B1) in the same tumor cells at both RNA and protein levels. Ectopic TSPY expression in cultured cells up-regulates progrowth genes, including those at chromosome 12p13, frequently gained/amplified in TGCTs. Our results suggest that TSPY, in combination with other markers, could be an important marker for diagnosis and subclassification of TGCTs and support its role in the pathogenesis of both gonadoblastoma and TGCTs.
AB - The testis-specific protein Y-encoded (TSPY) gene is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY) that predisposes dysgenetic gonads of intersex patients to gonadoblastoma development. TSPY is expressed at high levels in gonadoblastoma tissues, supporting its possible oncogenic function in this type of germ cell tumors. To explore the possibility that this Y chromosome gene is also involved in pathogenesis of the more common testicular germ cell tumors (TGCTs), we have conducted various expression studies using immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction analysis on 171 cases of TGCTs and selected normal testis controls. Our results demonstrated that TSPY protein is abundantly expressed in the precursor, carcinoma in situ or intratubular germ cell neoplasia unclassified, and seminoma, but only minimally or not expressed in various types of nonseminomas. TSPY coexpresses with established germ cell tumor markers (such as placental-like alkaline phosphatase, c-KIT, OCT4) and proliferative markers (such as Ki-67 and cyclin B1) in the same tumor cells at both RNA and protein levels. Ectopic TSPY expression in cultured cells up-regulates progrowth genes, including those at chromosome 12p13, frequently gained/amplified in TGCTs. Our results suggest that TSPY, in combination with other markers, could be an important marker for diagnosis and subclassification of TGCTs and support its role in the pathogenesis of both gonadoblastoma and TGCTs.
KW - Biomarkers, Tumor/analysis
KW - Blotting, Western
KW - Cell Cycle Proteins/biosynthesis
KW - Gene Expression
KW - Humans
KW - Immunohistochemistry
KW - Male
KW - Neoplasms, Germ Cell and Embryonal/genetics
KW - Oligonucleotide Array Sequence Analysis
KW - RNA, Messenger/analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Testicular Neoplasms/genetics
UR - http://www.scopus.com/inward/record.url?scp=34548684348&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2007.03.011
DO - 10.1016/j.humpath.2007.03.011
M3 - Article
C2 - 17521702
SN - 0046-8177
VL - 38
SP - 1470
EP - 1481
JO - Human pathology
JF - Human pathology
IS - 10
ER -