Estrogen receptor-negative
breast carcinomas are more aggressive and are unresponsive to anti-
estrogens. Thus, they clearly require new
therapies targeted against specific genes and
proteins actively engaged in the pathophysiology of
cancer. The
S-phase kinase-associated protein Skp2 is required for the
ubiquitin-mediated degradation of the
cdk-inhibitor p27 and is a bona fide proto-
oncoprotein. We attempted to explore whether Skp2 may be a potential specific therapeutic target in the subset of aggressive
breast carcinomas by investigating the possible relationship between expression of Skp2 and p27
proteins and
estrogen receptor (ER). Immunohistochemical analysis of
tumor tissues was employed to determine the expression of Skp2, p27, and ER
proteins in 82 cases of primary
breast carcinoma. Higher levels of Skp2 were detected more frequently in ER-negative
tumors and
tumors metastatic to the axillary lymph nodes. The expression of p27 was inverse with the histologic grade. Statistical analysis showed that the percentage of high Skp2 expressors was significantly greater in the group with low p27 expression than in the group with high p27 expression. The current study, together with the results from a previous study, demonstrated the existence of a subtype of high-grade, negative ER
breast carcinomas with high Skp2 and low p27 levels. This implies that Skp2 may be a potential specific therapeutic target in a subset of aggressive
breast carcinomas. Thus far, there is no specific
therapy for the ER-negative and HER-2/neu resistant groups, which are among the subset of aggressive
tumors.