IS P53 EXPRESSION, DETECTED BY IMMUNOHISTOCHEMISTRY, AN IMPORTANT PARAMETER OF RESPONSE TO TREATMENT IN TESTIS CANCER

Background: Several prior studies revealed positive ;p53 expression vi a immunohistochemistry (IHC) in a large percentage of germ cell testic ular cancers (GCTTs). However; the predicting and prognostic value of this protein remains to be defined. Therefore, the aim of our study wa s to further clarify the role of p53 protein in GCITs and to look for correlations between its gene expression and other disease parameters, including histological subtype, stage and clinical resistance/sensiti vity. Furthermore, we correlated p53 protein expression with that of M DRI gene product protein (Pgp) in older to examine the interrelationsh ip between these two markers. Patients and methods: 77 untreated patie nts with GCTTs were investigated for their p53 expression using monocl onal antibody and immunohistochemistry in paraffin-embedded specimens. There were 34 patients with stage I, 16 with stage II, 27 with stage III disease. Results: All tumor types, except differentiated teratomas , were immunoreactive for p53 to a various extent ranging from scarcel y positive to homogeneously stained tumor cells. Seminomas (S) and emb ryonal carcinoma (EC) components showed the most positive nuclear stai ning. p53 expression showed a significant inverse correlation with the stage of disease (P<0.0003). There was a significant positive relatio nship between p53 immunoreactivity and response to treatment (P=0.0012 ), i.e. high levels of p53 expression correlated with clinical sensiti vity of the tumors to chemotherapy. We could demonstrate a statistical ly significant opposite relationship between p53 and Pgp immunoreactiv ity (P<0.0005). Conclusion: Our results show that p53 status in tumor cells may be a strong determinate of susceptibility to chemotherapy an d that p53 overexpression has a favourable prognosis in terms of respo nse to treatment in GCTTs. Moreover, the findings provide clinical evi dence for the presence of significant relationship between p53 and MDR 1/Pgp immunoreactivity. They also suggest that patients resistant to c hemotherapy and lacking p53 expression might benefit from an alternati ve appropriately designed chemotherapeutic regimen to achieve further successful treatment in GCTTs.