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

We used image cytometry to quantify the immunohistochemical expression of p 21(waf-1) and p53 in primary breast carcinoma. Ratio analysis of the quanti fied p53/p21(waf-1) protein expression allowed us Co define 3 groups of car cinomas, each characterized by specific pathological and biological profile s. The negative (NEG) group, characterized by negligible expression of both proteins, comprised small-sized, low-grade tumors associated with high con tents of hormonal receptors and low growth fraction. In the NEG group, Ki-6 7 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 an d high growth fraction, In the P53H group, both p53 and Ki-67 were inversel y associated with both estrogen receptor (ER) and progesterone receptor (PC R), suggesting that: extensive p53 immunostaining is related to poor differ entiation and high proliferation. Only hi status was prognostically signifi cant in the P53H group. The P21H group, characterized by lence of p21(waf-1 ) %LIa, displayed intermediate pathological and biological features. A sign ificant association between p53 and p21(waf-1) expression suggested functio nal stabilization of wtp53 and therefore possible DNA damage-dependent GI/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 NEC group. Proportional hazard r egression analysis disclosed Ki-67 %LIa and, to a lesser degree, PCR %LIa a s significant relapse-free survival prognostic indicators. (C) 2001 Wiley-L iss. Inc.