Biological markers of cisplatin resistance in advanced testicular germ cell tumours. 2012

Adelaida García-Velasco, and Ignacio Durán, and Elena García, and Miquel Tarón, and Claudio Ballestín, and Daniel Castellanos, and Hernán Cortés-Funés, and Luis Paz-Ares
Centro Integral Oncológico Clara Campal, Hospital Norte de Madrid Sanchinarro, C/ Oña, 10, ES-28050 Madrid, Spain. adelaidagarcia@hospitaldemadrid.com

BACKGROUND Germ cell tumours (GCTs) of the testis show exquisite sensitivity to treatment with cisplatin. Despite the high cure rates provided by platinum-based chemotherapy, 10-20% of patients die from progressive disease. Although various cellular pathways may influence cisplatin efficacy, their actual impact has not been comprehensively investigated in advanced GCTs. The objective of the present study was to clarify the role of the expression status of proteins involved in the Rb and p53 tumour suppressor pathways in sensitivity and resistance of GCTs to cisplatin-based chemotherapy. METHODS Paraffin-embedded tumour tissues from 84 patients with advanced GCT treated with cisplatin-based chemotherapy were analysed. Immunohistochemical expression of proteins p53 and mdm2, and the G1-phase cyclins D1 and D2 (CD1 and CD2) was assessed and correlated with the clinical course. RESULTS The percentages of positive expression of p53, mdm2, CD1 and CD2 were 56, 57, 37.5 and 55%, respectively. From univariate analysis, there was no significant association between p53, mdm2 or CD1 expression and outcome. Instead, positive CD2 expression was found to be marginally associated with shorter median duration of progression-free survival (PFS) (p=0.06). In multivariate analysis, none of the molecular markers retained statistical significance with treatment response or survival. CONCLUSIONS Tissular expression of p53, mdm2 and CD1 is not associated with prognosis or treatment response in patients with advanced GCT. Aberrant CD2 expression appears to further determine a shorter PFS. Larger and further studies are required to validate CD2 as a marker of cisplatin resistance.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D009373 Neoplasms, Germ Cell and Embryonal Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS. Germ Cell Cancer,Germ Cell Tumor,Neoplasms, Embryonal and Mixed,Cancer, Embryonal,Cancer, Embryonal and Mixed,Embryonal Neoplasms,Germ Cell Neoplasms,Germ Cell and Embryonal Neoplasms,Germ Cell and Embryonic Neoplasms,Neoplasms, Embryonal,Neoplasms, Germ Cell,Neoplasms, Germ Cell and Embryonic,Cancer, Germ Cell,Cancers, Embryonal,Cancers, Germ Cell,Embryonal Cancer,Embryonal Cancers,Embryonal Neoplasm,Germ Cell Cancers,Germ Cell Tumors,Neoplasm, Embryonal,Tumor, Germ Cell,Tumors, Germ Cell
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013736 Testicular Neoplasms Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms. Cancer of Testis,Cancer of the Testes,Testicular Cancer,Testicular Neoplasm,Testicular Tumor,Testis Cancer,Cancer of the Testis,Neoplasms, Testicular,Neoplasms, Testis,Testicular Tumors,Testis Neoplasms,Tumor of Rete Testis,Cancer, Testicular,Cancer, Testis,Cancers, Testicular,Cancers, Testis,Neoplasm, Testicular,Neoplasm, Testis,Rete Testis Tumor,Rete Testis Tumors,Testicular Cancers,Testis Cancers,Testis Neoplasm,Testis Tumor, Rete,Testis Tumors, Rete,Tumor, Testicular,Tumors, Testicular
D014408 Biomarkers, Tumor Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or BODY FLUIDS. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including HORMONES; ANTIGENS; amino and NUCLEIC ACIDS; ENZYMES; POLYAMINES; and specific CELL MEMBRANE PROTEINS and LIPIDS. Biochemical Tumor Marker,Cancer Biomarker,Carcinogen Markers,Markers, Tumor,Metabolite Markers, Neoplasm,Tumor Biomarker,Tumor Marker,Tumor Markers, Biochemical,Tumor Markers, Biological,Biochemical Tumor Markers,Biological Tumor Marker,Biological Tumor Markers,Biomarkers, Cancer,Marker, Biochemical Tumor,Marker, Biologic Tumor,Marker, Biological Tumor,Marker, Neoplasm Metabolite,Marker, Tumor Metabolite,Markers, Biochemical Tumor,Markers, Biological Tumor,Markers, Neoplasm Metabolite,Markers, Tumor Metabolite,Metabolite Markers, Tumor,Neoplasm Metabolite Markers,Tumor Markers, Biologic,Tumor Metabolite Marker,Biologic Tumor Marker,Biologic Tumor Markers,Biomarker, Cancer,Biomarker, Tumor,Cancer Biomarkers,Marker, Tumor,Markers, Biologic Tumor,Markers, Carcinogen,Metabolite Marker, Neoplasm,Metabolite Marker, Tumor,Neoplasm Metabolite Marker,Tumor Biomarkers,Tumor Marker, Biochemical,Tumor Marker, Biologic,Tumor Marker, Biological,Tumor Markers,Tumor Metabolite Markers
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D051736 Proto-Oncogene Proteins c-mdm2 An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF. Mdm2 Protein,c-mdm2 Proto-Oncogene Protein,Double Minute 2 Protein,MDMX Protein,Mdm-2 Protein,Murine Double Minute 2 Protein,Mdm 2 Protein,Proto Oncogene Proteins c mdm2,Proto-Oncogene Protein, c-mdm2,c mdm2 Proto Oncogene Protein,c-mdm2, Proto-Oncogene Proteins

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