Biological markers of cisplatin resistance in advanced testicular germ cell tumours.
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.
Centro Integral Oncológico Clara Campal, Hospital Norte de Madrid Sanchinarro, C/ Oña, 10, ES-28050 Madrid, Spain. adelaidagarcia@hospitaldemadrid.com
Adelaida
A
García-Velasco
Ignacio
I
Durán
Elena
E
García
Miquel
M
Tarón
Claudio
C
Ballestín
Daniel
D
Castellanos
Hernán
H
Cortés-Funés
Luis
L
Paz-Ares
D018949:Antigens, CD1 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018801:CD2 Antigens / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018949:Antigens, CD1; D014408:Biomarkers, Tumor; D018801:CD2 Antigens; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002945:Cisplatin