Apoptosis in epithelial ovarian tumours: Prognostic significance of clinical and histopathologic factors and its association with the immunohistochemical expression of apoptotic regulatory proteins (p53, bcl-2 and bax)

Abstract

Objective The objective was to establish the importance of apoptosis-related genes and the apoptotic index (AI) as prognostic factors in patients with epithelial ovarian tumours. Material and methods Tumour specimens from 130 epithelial ovarian tumours were examined for expression of p53, bcl-2 and bax proteins. The apoptotic index was evaluated by modified terminal deoxynucleotide-transferase-mediated digoxigenin triphosphate-biotin nick end-labelling (TUNEL) methods and by haematoxylin–eosin (H–E) staining. Other clinical and histopathological variables were also analysed. Statistical analyses were performed using the SPSS 10.0 package. Results The apoptotic index detected by H–E and enzymatic assay was high in the majority of carcinomas (serous, endometrioid and clear cell ( p = 0.001). In the univariate survival analysis, high apoptotic index, high p53 and low bcl-2 expression, significantly correlated with shorter survival and shorter disease-free periods ( p < 0.01). In multivariate analysis the age ( p = 0.026; CI: 1.035–1.066 and p = 0.011; CI: 1.835–2.077), FIGO stage ( p = 0.017; CI: 1.385–4.514 and p = 0.024; CI: 1.217–1.940), p53 expression ( p = 0.03; CI: 1.017–1.627 and p = 0.02; CI: 1.050–2.350) and apoptotic index ( p = 0.019; CI: 1.375–1.750 and p = 0.019; CI: 1.442–2.085) were revealed to be independent prognostic factors for survival and recurrence, respectively. Conclusions Our results indicate that the apoptotic index and p53 nuclear accumulation are independent predictive factors of recurrence and short survival. Our data also suggest different patterns of alterations for the various tumour types.