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Published on: October 9, 2013
Spindle proteins are differentially expressed in the various histological subtypes of testicular germ cell tumors
Espen Burum-Auensen1, Rolf I Skotheim, Aasa R Schjølberg
1Division of Pathology, Medical Faculty, University of Oslo, Rikshospitalet, Oslo University Hospital, Oslo, Norway.
Background:
Testicular germ cell tumors (TGCTs) are characterized by an aneuploid DNA content. Aberrant expression of spindle proteins such as the Aurora kinases and the spindle checkpoint proteins MAD2 and BUB1B, are thought to contribute to the development of chromosomal instability and DNA aneuploidy in cancer. The importance of these spindle proteins remains unknown in the development of TGCTs, thus we have explored the expression levels of these proteins in normal and malignant testicular tissues.
Materials And Methods:
Using tissue microarrays the expression levels of Aurora kinase A (AURKA), Aurora kinase B (AURKB), BUB1B and MAD2 were measured in normal, preneoplastic and malignant testicular tissues of different histological subtypes from 279 orchidectomy specimens by means of immunohistochemistry.
Results:
All the spindle proteins except for AURKB were expressed in normal testis. Sixty-eight and 36%, respectively, of the primary spermatocytes in the normal testis were positive for BUB1B and MAD2, while only 5% of the cells were positive for AURKA. There was a significantly lower expression of the spindle checkpoint proteins in carcinoma in situ compared to normal testis (P=0.008 and P=0.043 for BUB1B and MAD2, respectively), while the level of AURKA was increased, however, not significantly (P=0.18). The extent of spindle protein expression varied significantly within the different histological subtypes of TGCTs (P<0.001 for AURKB, BUB1B and MAD2, P=0.003 for AURKA). The expression of AURKA was significantly elevated in both non-seminomas (P=0.003) and seminomas (P=0.015). The level of BUB1B was significantly decreased in non-seminomas (P<0.001). A similar tendency was observed for MAD2 (P=0.11).
Conclusions:
In carcinoma in situ of TGCTs the spindle checkpoint proteins MAD2 and BUB1B are significantly less expressed compared to normal testis, while the expression of AURKA is increased. We suggest that these changes may be of importance in the transition from in situ to invasive testicular cancer.
Insights
Testicular germ cell tumors (TGCTs) show altered expression of spindle proteins. Spindle checkpoint proteins MAD2 and BUB1B are decreased, while AURKA increases in carcinoma in situ, potentially driving cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Testicular germ cell tumors (TGCTs) are characterized by aneuploid DNA content.
- Aberrant expression of spindle proteins like Aurora kinases and spindle checkpoint proteins (MAD2, BUB1B) is linked to chromosomal instability and aneuploidy in cancer.
- The role of these spindle proteins in TGCT development is not well understood.
Purpose of the Study:
- To investigate the expression levels of key spindle proteins (AURKA, AURKB, BUB1B, MAD2) in normal, preneoplastic, and malignant testicular tissues.
- To determine the association of these proteins with different histological subtypes of TGCTs.
Main Methods:
- Immunohistochemistry was used to measure the expression of AURKA, AURKB, BUB1B, and MAD2.
- Tissue microarrays from 279 orchidectomy specimens, including normal, preneoplastic, and malignant testicular tissues, were analyzed.
Main Results:
- AURKB was the only spindle protein not detected in normal testis; AURKA, BUB1B, and MAD2 showed varying expression in normal primary spermatocytes.
- Carcinoma in situ showed significantly lower expression of BUB1B and MAD2, and increased AURKA compared to normal testis.
- Expression levels of AURKA, AURKB, BUB1B, and MAD2 varied significantly across different TGCT histological subtypes. AURKA was elevated in both seminomas and non-seminomas, while BUB1B was decreased in non-seminomas.
Conclusions:
- In carcinoma in situ, spindle checkpoint proteins MAD2 and BUB1B are significantly downregulated, while AURKA is upregulated.
- These observed changes in spindle protein expression may play a crucial role in the transition from in situ to invasive testicular cancer.
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