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Biological markers of cisplatin resistance in advanced testicular germ cell tumours

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Abstract

Introduction

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 cisplatinbased chemotherapy.

Materials and methods

Paraffin-embedded tumour tissues from 84 patients with advanced GCT treated with cisplatinbased 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.

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Authors and Affiliations

  1. Centro Integral Oncológico Clara Campal, Hospital Norte de Madrid Sanchinarro, C/ Oña, 10, ES-28050, Madrid, Spain

    Adelaida García-Velasco, Ignacio Durán & Elena García

  2. Laboratorio de Investigación, Hospital Germans Trias y Pujols, Badalona, Barcelona, Spain

    Miquel Tarón

  3. Hospital Universitario 12 de Octubre, Madrid, Spain

    Claudio Ballestín, Daniel Castellanos & Hernán Cortés-Funés

  4. Hospital Universitario Virgen del Rocío, Sevilla, Spain

    Luis Paz-Ares

Authors
  1. Adelaida García-Velasco
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  2. Ignacio Durán
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  3. Elena García
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  4. Miquel Tarón
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  5. Claudio Ballestín
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  6. Daniel Castellanos
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  7. Hernán Cortés-Funés
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  8. Luis Paz-Ares
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Correspondence to Adelaida García-Velasco.

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García-Velasco, A., Durán, I., García, E. et al. Biological markers of cisplatin resistance in advanced testicular germ cell tumours. Clin Transl Oncol 14, 452–457 (2012). https://doi.org/10.1007/s12094-012-0823-1

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  • DOI: https://doi.org/10.1007/s12094-012-0823-1

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