ABSTRACT
Drug resistance is one of the most important clinical problems in the treatment of ovarian cancer. This study was designed to determine whether expression of p53 could be used as a marker for predicting the response to chemotherapy of ovarian cancer. Tissue blocks were obtained from 187 patients with diagnosed untreated ovarian cancer. Paraffin sections from the primaries were immunohistochemically analysed for p53 expression. All patients underwent platinum-based chemotherapy after surgery. We analysed whether the number of chemotherapy cycles was related to survival in women with p53 positive and p53 negative ovarian cancer. 27/187 cases were p53 positive. Expression of p53 was associated with other factors of unfavourable prognosis. Patients with p53 positive tumours had a significantly worse prognosis compared with patients with p53 negative tumours (P = 0.037). There was a statistically significant dose-response effect of platinum-based chemotherapy in patients with p53 negative tumours, which could not be seen in patients with p53 positive tumours (P = 0.01 versus P = 0.553). This could also be observed in patients with residual tumour after surgery (P = 0.0001 versus P = 0.8866). Expression of p53 may be an additional useful marker in predicting response to chemotherapy. Thus, it is possible to identify a subgroup of patients who may benefit from alternative therapy regimens.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Genes, p53 , Neoplasm Proteins/metabolism , Ovarian Neoplasms/drug therapy , Tumor Suppressor Protein p53/metabolism , Adult , Aged , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Female , Follow-Up Studies , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/surgery , Survival Analysis , Survival Rate , Treatment OutcomeABSTRACT
The prognostic value of various molecular markers, which adequately account for the tumor biology and disease behaviour of ovarian cancer, is still unclear. Recent studies have focused on the role of genes regulating the balance between proliferation and cellular suicide, apoptosis. In the present study, tumor tissue from 215 patients with ovarian cancer was immunohistochemically analysed for Bax- and Bcl-2-expression. There was an association between Bcl-2-expression (30%) and factors of favourable prognosis. In contrast, Bax-expression (47%) was related to bad clinical outcome, especially in cases without concomitant Bcl-2-expression. In patients with Bcl-2-positive/Bax-negative tumors, overall survival was significantly longer (p = 0.0379) than in patients with Bcl-2- and Bax-negative tumors. Respectively, expression of Bax without Bcl-2-expression was correlated with bad clinical outcome (p = 0.033). The difference in overall survival was most striking (p = 0.0007) between patients with Bax-positive/Bcl-2-negative and Bcl-2-positive/Bax-negative tumors. This could also be demonstrated for the various subgroups of different tumor grade and stage. It may be speculated, that alteration of the Bax/Bcl-2-balance may influence the clinical course by deregulation of programmed cell death and altered sensitivity to chemotherapy.
