Drug resistance and sensitivity of germ cell testicular tumors: evaluation of clinical relevance of MDR1/Pgp, p53, and metallothionein (MT) proteins.

ABSTRACT

BACKGROUND: Although in vitro and clinical studies indicate that overexpression of P-glycoprotein (Pgp), p53, or metallothionein (MT) is involved in modulating drug resistance/sensitivity of cancer cells, the clinical relevance of the overexpression remains to be elucidated. MATERIALS AND METHODS: In this paper the expression and clinical value of Pgp, p53, and MT were evaluated immunohistochemically in 77 specimens of germ cell testicular tumors (GCT). We also studied the interrelationship(s) between the investigated markers. RESULTS: Pgp positivity correlated with cancers of advanced stages (P = 0.000). p53 and MT immunostaining does not predict a poor response to chemotherapy, but rather is correlated to a favorable clinical outcome (P = 0.001, P = 0.00006 respectively). We obtained an inverse association between Pgp and p53 (P = 0.0005), and positive strong association between p53 and MT immunoreactivity (P = 0.0002). CONCLUSIONS: Based on our results in patients with germ cell testicular tumors we assume that the poor clinical outcome seen in certain Pgp positive tumors is the consequence of Pgp association with a more progressive malignant phenotype, rather than its role in multidrug resistance (MDR). p53 and MT immunoreactivity predicts a better response rate to chemotherapy, wheres tumors lacking or demonstrating low MT and or p53 expression show a worse prognosis.