RESUMEN
BACKGROUND: Testicular germ cell tumors (TGCTs) are highly sensitive to platinum-based chemotherapy, and wild-type p53 seems to play a pivotal role in this susceptibility. On the other hand, overexpression of MDM2 seems to entail treatment resistance and unfavorable prognosis. OBJECTIVES: We aimed to describe p53 and MDM2 immunoexpression in a well-characterized cohort of primary and metastatic TGCTs and evaluate associations with clinicopathological and prognostic variables, including survival. MATERIALS AND METHODS: 237 primary tumor samples and 12 metastases were evaluated for p53 and MDM2 immunoexpression using digital image analysis. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow-up. RESULTS: A significant positive correlation between p53 and MDM2 H-scores was found (rs = 0.590, P < .0001). Non-seminomas showed significantly higher expression levels of both p53 and MDM2 (P = .0002, P < .0001), which peaked in embryonal carcinomas and choriocarcinomas. Percentage of immunoexpressing cells and H-score were significantly higher in chemo-treated metastases compared with chemo-naïve primary tumors for MDM2 (P ≤ .0001 for both), but not for p53 (P = .919 and P = .703, respectively). Cases with higher MDM2 immunoexpression showed a statistically significant trend for association with poorer prognosis (P = .043). Relapse/progression-free survival at 12 months post-diagnosis was lower in the "MDM2-high" (≥P50) vs. the "MDM2-low" (Asunto(s)
Neoplasias de Células Germinales y Embrionarias/patología
, Proteínas Proto-Oncogénicas c-mdm2/metabolismo
, Neoplasias Testiculares/patología
, Proteína p53 Supresora de Tumor/metabolismo
, Adulto
, Biomarcadores de Tumor/metabolismo
, Supervivencia sin Enfermedad
, Resistencia a Antineoplásicos/fisiología
, Humanos
, Masculino
, Neoplasias de Células Germinales y Embrionarias/metabolismo
, Neoplasias de Células Germinales y Embrionarias/mortalidad
, Pronóstico
, Estudios Retrospectivos
, Neoplasias Testiculares/metabolismo
, Neoplasias Testiculares/mortalidad