DRUG-RESISTANCE AND SENSITIVITY OF GERM-CELL TESTICULAR-TUMORS - EVALUATION OF CLINICAL RELEVANCE OF MDR1 PGP, P53, AND METALLOTHIONEIN (MT) PROTEINS/

Backround: Although in vitro and clinical studies indicate that overex pression of P- glycoprotein (Pgp), p53, ol metallothionein (MT) is inv olved in modulating drug resistance/sensitivity of cancer cells, the c linical relevance of the overexpression remains to be elucidated. Mate rials 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 interrelatio nship(s) between the investigated markers. Results. Pgp positivity cor related with cancers of advanced stages (P = 0.000). p53 and MT immuno staining 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 = 0.00005), and positive strong association between p53 and MT immu noreactivity (P = 0.0002). Conclusions: Based on our results in patien ts with germ cell testicular tumors we assume that the poor clinical o utcome seen in certain Pgp positive tumors is the consequence of Pgp a ssociation with a more progressive malignant phenotype, rather than it s role in multidrug resistance (MDR). p53 and MT immunoreactivity pred icts a better response rate to chemotherapy, whereas tumors lacking oi demonstrating low MT and ol p53 expression show a worse prognosis.