VALUE OF P-GLYCOPROTEIN, GLUTATHIONE-S-TRANSFERASE-PI, C-ERBB-2, AND P53 AS PROGNOSTIC FACTORS IN OVARIAN CARCINOMAS

Purpose: To determine the prognostic value of immunostaining of P-glyc oprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. Patients and Metho ds: Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with plat inum- and doxorubicin-containing chemotherapy. The results of immunost aining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survi val. Results: P-gp and GST pi immunoreactivity were present in 13 (15% ) and 79 cases (89%), respectively, and were not associated with any o ther prognostic factor or PFS or overall survival. C-erbB-2 immunoreac tivity was present in 18 cases (20%) and was associated with undiffere ntiated histiotype (P < .05), but not with PFS or overall survival. p5 3 immunoreactivity was present in the nuclei of 31 cases (35%) and cyt oplasm of nine cases (10%). Nuclear p53 staining was associated with g rade III rumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was assoc iated with shorter PFS (relative risk [RR], 3.3; 95% confidence interv al [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8 ). After adjustment for presence of more than I-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognos tic significance in stage III/IV tumors, The frequency of P-gp stainin g in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated rumors (13 of 89 cases) (P < .001). No combin ation of prognostic parameters was able to predict response to chemoth erapy adequately. Conclusion: Nuclear immunoreactivity of p53 in ovari an carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing comb ination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemother apy.