Quantitative p21(waf-1)/p53 immunohistochemical analysis defines groups of primary invasive breast carcinomas with different prognostic indicators

Abstract

We used image cytometry to quantify the immunohistochemical expression of p21(waf-1) and p53 in primary breast carcinoma. Ratio analysis of the quantified p53/p21(waf-1) protein expression allowed us to define 3 groups of carcinomas, each characterized by specific pathological and biological profiles. The negative (NEG) group, characterized by negligible expression of both proteins, comprised small-sized, low-grade tumors associated with high contents of hormonal receptors and low growth fraction. In the NEG group, Ki-67 labelling index area (%LIa) was the only significant prognostic indicator. The P53H group, characterized by prevalence of p53 %LIa, was constituted by large-sized, high-grade tumors showing low hormonal receptor contents and high growth fraction. In the P53H group, both p53 and Ki-67 were inversely associated with both estrogen receptor (ER) and progesterone receptor (PGR), suggesting that extensive p53 immunostaining is related to poor differentiation and high proliferation. Only N status was prognostically significant in the P53H group. The P21H group, characterized by prevalence of p21(waf-1) %LIa, displayed intermediate pathological and biological features. A significant association between p53 and p21(waf-1) expression suggested functional stabilization of wtp53 and therefore possible DNA damage-dependent G1/S arrest (genetic instability) in the P21H group; P21(waf-1)expression was significantly associated with the presence of node metastasis. Patients in the P21H group had a higher recurrence rate and a shorter disease-free time interval from surgery with respect to the NEG group. Proportional hazard regression analysis disclosed Ki-67 %LIa and, to a lesser degree, PGR %LIa as significant relapse-free survival prognostic indicators.