Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas

Loss of function of the tumor suppressor gene p53, increased expression of glutathione-S-transferase pi (GST pi) and the major vault protein are invol ved in drug resistance of ovarian carcinomas. However, a study comparing th ese factors has not yet been performed. Therefore, paraffin-embedded materi al of 213 ovarian tumors with well-documented follow-up was used for immuno histochemical analysis of p53 protein, GST pi, and major vault protein (ant ibodies LRP-56, LMR-5). Forty-six percent of the cases showed nuclear p53 accumulation. Strong immu noreactivity for GST pi, LRP-56, and LMR-5 was seen in 50%, 36%, and 47%, r espectively. p53 positivity was most often found in serous carcinomas (p < 0.05). Strong GST pi expression was the only factor that correlated with cl inical resistance to chemotherapy (p = 0.04). In the whole group, as well a s in FIGO III cases stratified for residual disease less than or equal to a nd >2 cm, p53 and GST pi correlated with an adverse outcome (p = 0.01 for p 53 and p = 0.04 for GST-pi). Strong LRP-56 or LMR-5 staining was associated with a tendency towards poorer prognosis, without reaching statistical sig nificance. In multivariate analysis for FIGO III, only residual disease and p53 proved to be independent prognostic factors. Our observations confirm the prognostic significance of p53 accumulation in ovarian carcinomas. Only GST pi immunoreactivity was significantly correlated with drug resistance.