+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Immunohistochemical and mutational analysis of the P53 tumour suppressor gene and the bcl-2 oncogene in primary testicular germ cell tumours

, : Immunohistochemical and mutational analysis of the P53 tumour suppressor gene and the bcl-2 oncogene in primary testicular germ cell tumours. Apmis. 106(1): 90-100,.

The role of p53 in testicular germ cell tumours is still contradictory based on the finding of immunohistochemical overexpression at the protein level, but lack of mutations at the DNA level. In addition, p53 wild-type activity has been demonstrated in cell culture experiments. Overexpression of the proto-oncogene bcl-2 might block p53-induced apoptosis and might inhibit p53 functional activity. To clarify the apparent paradox with respect to p53 overexpression and lack of mutations, an immunohistochemical and mutational analysis of p53 and bcl-2 in TGCT was performed. Ten normal testes, 52 CIS and 151 clinical stage I nonseminomatous GCTs were included in our study. A commercially available anti-p53 polyclonal rabbit antibody and an anti-bcl-2-mouse monoclonal antibody were used to stain the 5pm sections. Staining was assessed by counting at least 500 cells from the area of the most intense staining in each tumour cell type, and this was scored semiquantitatively for intensity of staining on a 4 point scale. In addition, 30 primary GCTs were included in the mutational analysis: areas with p53 overexpression were identified and microdissected prior to DNA extraction. p53 exons 5-8 were amplified by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis. Templates demonstrating band shifts on SSCP were subjected to direct DNA sequence analysis. None of the normal testes, 32/52 (62%) CIS, and 142/151 (94%) germ cell tumours exhibited p53 overexpression. p53 expression was significantly lower in mature teratomas (0.8 +/- 0.2) than in other germ cell tumour components (2.8 +/- 1.2, p > 0.001). PCR-SSCP did not reveal any missense mutations or deletions for the p53 gene. Bcl-2 protein expression was observed in none of the normal testes, in none of the CIS, and in 14/151 (9.3%) germ cell tumours. 13/14 germ cell tumours demonstrated bcl-2 expression only in the glandular and stromal elements of their teratomatous components whereas all other components were negative for bcl-2. Our results--p53 overexpression, lack of p53 mutations, undetectable bcl-2--are consistent with recent in vitro studies. High susceptibility of testicular cancer to drug-induced apoptosis appears to be the result of wild-type p53 and lack of bcl-2. Radiation and chemotherapeutic insensitivity of mature teratomas might be the result of bcl-2 overexpression and lack of p53 overexpression. Therefore, chemoresistance to DNA damaging agents might be reflected by the expression of p53 and bcl-2 and it might be useful to evaluate p53 and bcl-2 in primary tumours and metastatic lesions in order to identify patients early with primary or secondary chemoresistance.


PMID: 9524567

DOI: 10.1111/j.1699-0463.1998.tb01324.x

Other references

Zupke, Mp, 1992: Meat now plays bit part in a healthy diet, but it's still part of the show. Meat eaters are being advised to limit meat intake to about six ounces per day. That in itself is a major change for most of us. But what about the type of meat you eat? Choosing the right (low-fat) cuts is just as important as how much you eat. T...

Cronin, TM., 1979: Foraminifer and ostracode species diversity in the Pleistocene Champlain Sea of the St Lawrence Lowlands. The Champlain Sea was a postglacial body of marine to brackish water that inundated the St. Lawrence Lowlands after the retreat of the Laurentide Ice Sheet (12,500-10,000 yr BP). Champlain Sea foraminifer and ostracode species diversities were ana...

Moises, V.A.; Maciel, B.C.; Swensson, R.E.; Valdes-Cruz, L.M.; Daily, P.O.; Sahn, D.J., 1989: Left coronary artery-to-pulmonary artery communication (a late postoperative complication after the Takeuchi procedure for repair of anomalous origin of left coronary artery from the pulmonary artery) detected by color Doppler flow mapping. American Heart Journal 118(2): 407-410

Jaiswal, P.B.; Davenport, P.W., 2016: Intercostal muscle motor behavior during tracheal occlusion conditioning in conscious rats. A respiratory load compensation response is characterized by increases in activation of primary respiratory muscles and/or recruitment of accessory respiratory muscles. The contribution of the external intercostal (EI) muscles, which are a primary...

Alireza Karimzadeh Somarin; Paul Ashley, 2004: Hydrothermal alteration and mineralisation of the Glen Eden Mo-W-Sn deposit; a leucogranite-related hydrothermal system, southern New England Orogen, NSW, Australia. The Glen Eden Mo-Sn-W deposit in north-eastern New South Wales, Australia, is an example of a leucogranite-related, low-grade, large-tonnage hydrothermal system. It occurs in the southern part of the New England Orogen and is hosted within Permian...

Tobe, K.; Tamemoto, H.; Yamauchi, T.; Aizawa, S.; Yazaki, Y.; Kadowaki, T., 1995: Identification of a 190-kDa protein as a novel substrate for the insulin receptor kinase functionally similar to insulin receptor substrate-1. Recently, we generated mice with a targeted disruption of the insulin receptor substrate-1 (IRS-1) gene and demonstrated that they exhibited growth retardation and mild insulin resistance, suggesting the presence of IRS-1-independent pathway that...

Hellema, H., 1991: "Life termination" in the Netherlands. Bmj 302(6783): 984-985

Smart, H.L.; Nicholson, D.A.; Atkinson, M., 1986: Gastro-oesophageal reflux in the irritable bowel syndrome. Symptomatic assessment and oesophageal investigations were done in 25 consecutive patients with the irritable bowel syndrome attending a gastroenterological clinic. Symptoms of gastro-oesophageal reflux, dysphagia, and a globus sensation were sign...

Rousset A., 1980: Biometrical study of the ovarian growth in chrysopa perla under optimal diet and under mal nutrition neuroptera chrysopidae. Female C. perla needs a diet containing protein, during the preoviposition stage after the emergence of the imago, for normal development of the oocytes. During the first 3 days ovarian growth is exponential (V = VoKt). For an optimal diet and sel...

Spittell, J.A.; Schirger, A.; Harrison, E.G.; Bulbulian, A.H., 1964: Vascular Clues To Occult Diseases. Postgraduate Medicine 35: 189-201