PROGNOSTIC VALUE OF P53 EXPRESSION IN EARLY-STAGE BREAST-CARCINOMA COMPARED WITH TUMOR ANGIOGENESIS, EPIDERMAL GROWTH-FACTOR RECEPTOR, C-ERBB-2, CATHEPSIN-D, DNA-PLOIDY, PARAMETERS OF CELL-KINETICS AND CONVENTIONAL FEATURES

p53 expression detected by immunocytochemistry is emerging as a novel potentially useful prognostic indicator in breast carcinoma. However, additional research is warranted because a consensus has not yet been achieved on: i) methodology and quality control issues; ii) its associ ation with other new biological prognostic indicators; iii) its progno stic value in multivariate analysis including conventional and new pat hobiological features and; iv) its clinical usefulness either as a pro gnostic and predictive factor. This study was undertaken in a series o f 165 early-stage breast cancer patients (median follow-up of 5 years) to compare the prognostic role of p53 expression with that of several other markers that have been found to be of value, using a multivaria te statistical analysis. These factors are: tumour angiogenesis, epide rmal growth factor receptor (EGFR), c-erbB-2 expression, cathepsin D, growth fraction by Ki-67 antibody, DNA ploidy and S-phase fraction. Th e main results observed were: i) 47 of 165 (28.5%) carcinomas had pAb 1801 staining and were considered as p53-positive; ii) p53 expression was weakly associated with S-phase fraction by flow cytometry (OR=1.86 ; p=0.085); iii) p53 expression was significantly associated with recu rrence (p53 negative [-] versus weak positive [+] tumours: p=0.07 and odds ratio of 2.21; p53 negative [-] versus high positive [++] tumours : p=0.01 and odds ratio of 2.86) and death (p53-versus +: p=0.53 and o dds ratio of 1.35; p53- versus ++: p=0.05 and odds ratio of 2.53); iv) the determination of p53 is able to identify a subset of high risk pa tients in c-erbB-2 negative tumours, this group being generally consid ered at good prognosis; v) In multivariate analysis on relapse-free su rvival including all the above markers only tumour angiogenesis, cathe psin D, EGFR and S-phase fraction and nodal status retained significan ce, and for overall survival only tumour angiogenesis was significant and independent. This new information on p53 expression could be usefu l to the clinician for a more rationale approach in defining prognosis of breast cancer patients. The prognostic value of p53 depends on whi ch other markers are additionally analyzed and previous studies have n ot always assayed tumour angiogenesis, which is the most important fac tor in this series. p53 still need to be assessed as a potential predi ctor of response to chemo or radiotherapy, because of its role in moni toring DNA damage.