Role of P53 and MDM2 in Treatment Response of Human Germ Cell Tumors

• DOI: 10.1200/jco.2002.20.6.1551
• Publication Date: 2017-02-24T08:46:10Z
• Authors: Anne-Marie F. Ker...; Frank Mayer; Michel Molier; Pascale C. van We...; J. Wolter Oosterhuis; Carsten Bokemeyer; Leendert H.J. Loo...
• Keywords: Male; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; DNA Mutational Analysis; Nuclear Proteins; Proto-Oncogene Proteins c-mdm2; Immunohistochemistry; Seminoma; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Testicular Neoplasms; Proto-Oncogene Proteins; Humans; Tumor Suppressor Protein p53; In Situ Hybridization; Polymorphism, Single-Stranded Conformational

PURPOSE: Testicular germ cell tumors (TGCTs) of adolescents and adults are very sensitive to systemic treatment. The exquisite chemosensitivity these cancers has been attributed a high level wild-type P53. MATERIALS AND METHODS: To clarify the role P53 in treatment sensitivity resistance TGCTs, we performed immunohistochemistry Western blotting analysis on series 39 fresh-frozen primary TGCTs before therapy (unselected series). In formalin-fixed paraffin-embedded patients with fully documented clinical course, including treatment-sensitive (n = 17) -resistant 18) tumors, status was assessed by mutation analysis. addition, involvement MDM2, antagonist, investigated immunohistochemistry, reverse transcriptase polymerase chain reaction, situ hybridization. RESULTS: Immunohistochemistry demonstrated absence staining for 36%, 41%, 17% unselected, responding, nonresponding respectively. Of positive most ie, 49%, 33%, showed 1% 10% nuclei. This overall low confirmed blotting. Mutation revealed only one silent responding patients. All embryonal carcinomas were homogeneously encoded full length mRNA, while heterogeneous pattern found other histologic components. Amplification MDM2 detected out 12 carcinomas. CONCLUSION: Although our results line previous findings presence they show that does not relate directly inactivation is common event development cisplatin resistance.