Quantitative p21(waf-1)/p53 immunohistochemical analysis defines groups of primary invasive breast carcinomas with different prognostic indicators.
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.
Laboratorio di Immunocitopatologia Oncologica, Dipartimento di Oncologia ed Ematologia, Università di Bologna, Bologna, Italy.
C
C
Ceccarelli
D
D
Santini
P
P
Chieco
C
C
Lanciotti
M
M
Taffurelli
G
G
Paladini
D
D
Marrano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004249:DNA Damage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019044:Image Cytometry; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53