624 Background: P27kip1 is a nuclear protein that controls the cell cycle by inhibiting cyclin dependent kinases. In breast cancer cell lines, both estrogen and her-2/neu degrade p27 through the ubiquitin-proteasome pathway. T1N0M0 breast cancers with high p27 expression have excellent long-term survival (Loda et al, Cancer Research 1998), now we examine the association of low p27 and other prognostic factors in these patients. Methods: 122 T1N0M0 infiltrating ductal carcinoma were examined using immunohistochemistry. Specific monoclonal antibodies were used against estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, p53 and p27. Percentage of cells stained were considered negative (or low for p27) if: ER <10%, PR <10%, p53<40%, her-2/neu DAKO score ≤ 1+, p27 (nuclear stain) <50%. Results: In T1a/bN0M0 tumors, 4/5 (80%) of low p27 tumors were also hormone receptor negative, while only 5/63 (8%) of the high p27 tumors were hormone receptor negative (P< 0.001, Fisher’s exact test). Although T1cN0M0 tumors showed a similar trend [4/12 (33%) of low p27 vs. 7/42 (17%) of high p27 tumors were hormone receptor negative], the difference was not statistically significant. No correlation was seen between low p27, her-2/neu, or p53 mutation. Conclusion: There is an association of low p27 and loss of hormone receptors in T1a/bN0M0 breast cancers, which may identify a subset of patients with a worse prognosis. Exploring the causes of p27 dysregulation (e.g., ubiquitin ligase overexpression) may shed further light on the significance of these associations. [Table: see text] No significant financial relationships to disclose.
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