Recognizing features that are dissimilar in male and female breast cancer: expression of p21Waf1 and p27Kip1 using an immunohistochemical assay.
BACKGROUND
Male breast cancer (MBC) is an uncommon disease, and most of our current knowledge of its biology, natural history and treatment has been extrapolated from data on the disease in women. Information is still needed on the molecular biological properties of male breast tumors and their predictive relevance. Kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 negatively regulate cell cycle progression by preventing the passage of cycling cells from G1 to S phase through G1 cyclin-dependent kinase activation. No studies exist on the role of these factors in male breast carcinoma.


METHODS
We have retrospectively analyzed the immunohistochemical expression of p21Waf1 and p27Kip1 protein in 27 primary MBC and in 101 female breast cancers (FBC) treated at the European Institute of Oncology between 1997 and 2000. We also assessed sex hormone receptors status, p53, bcl-2 and c-erb-B2 protein expression, and Ki-67 labeling index.


RESULTS
We observed a statistically significant difference in the immunostaining of KIPs p27Kip1 and p21Waf1 in male patients compared with females. Expression of p21Waf1 was observed in 19 of the 27 (70.3%) primary MBCs versus 29 of 101 FBC (29%). Fourteen of 22 negative c-erbB-2 MBCs cases expressed immunostaining for p21Waf1 (P = 0.05). p27Kip1 immunoreactivity was been detected in 26 of 27 (96.2%) male breast patients versus 39 of 101 FBC (39.3%) (P = 0.000). Highly positive staining for P27Kip1 was found in 21 of 25 androgen receptor-expressing samples. Higher levels of p27Kip1 were expressed in bcl-2-positive samples (17 of 20). Eighteen of 22 c-erbB-2-negative cases were strongly immunoreactive for p27Kip1.


CONCLUSIONS
p27Kip1 and p21Waf1 immunoreactivity is higher in MBCs compared with FBCs. The findings of higher p27Kip1 and p21Waf1 immunostaining may be an additional predictive factor in MBC. These biological features could be possible indicators for different biological pathways in the tumorigenesis of MBCs.
Curigliano
G
G
Department of Medicine, European Institute of Oncology, Milan, Italy. giuseppe.curigliano@ieo.it
Colleoni
M
M
Renne
G
G
Mazzarol
G
G
Gennari
R
R
Peruzzotti
G
G
de Braud
E
E
Robertson
C
C
Maiorano
E
E
Veronesi
P
P
Nolè
F
F
Mandalà
M
M
Ferretti
G
G
Viale
G
G
Goldhirsch
A
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D011336:Probability; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012737:Sex Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; D015689:Oncogene Protein p21(ras)