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Quantitative p21 WAF‐1 /p53 immunohistochemical analysis defines groups of primary invasive breast carcinomas with different prognostic indicators
Author(s) -
Ceccarelli C.,
Santini D.,
Chieco P.,
Lanciotti C.,
Taffurelli M.,
Paladini G.,
Marrano D.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20010320)95:2<128::aid-ijc1022>3.0.co;2-d
Subject(s) - immunohistochemistry , oncology , primary (astronomy) , pathology , medicine , biology , physics , astronomy
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 wt p53 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. © 2001 Wiley‐Liss, Inc.