Low p27Kip1 Expression Is an Independent Adverse Prognostic Factor in Patients with Multiple Myeloma

Purpose: To determine the clinical relevance of p27 Kip1 in multiple myeloma (MM), we examined the relationship between p27 Kip1 expression at diagnosis and clinical as well as laboratory parameters, including response to chemotherapy and overall survival in 74 previously untreated patients with MM. Experimental Design: Expression of p27 Kip1 was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded bone marrow biopsies. p27 Kip1 expression was classified as low (≤5% p27 Kip1 -positive myeloma cells) or high (>5% p27 Kip1 -positive myeloma cells). Results: Low p27 Kip1 expression was observed in 23 (31%) patients. The response rate to standard dose chemotherapy (including vincristine, doxorubicin, and dexamethasone induction before high-dose chemotherapy) was 70%, with no significant difference between patients with low or high p27 Kip1 expression (83 versus 65%; P = 0.1). Kaplan-Meier analysis of all 74 patients revealed that patients with low p27 Kip1 expression had a significantly shorter overall survival (median, 3.7 years versus 4.7 years; P = 0.03) than those with high p27 Kip1 expression. Patients with high p27 Kip1 expression receiving high-dose chemotherapy experienced prolonged overall survival as compared with those with low p27 Kip1 expression (median not yet reached versus 2.9 years; P = 0.008). By multivariate Cox regression analyses, low p27 Kip1 ( P = 0.03), deletion of chromosome 13q14 ( P = 0.02), and β 2 -microglobulin ( P = 0.01) were identified as independent adverse prognostic factors for overall survival. According to the number of independent unfavorable prognostic factors present in each patient, low-risk, intermediate-risk, and high-risk patients with different overall survival times were defined (median overall survival, 6.3 versus 4.2 versus 1.8 years; P 0.001). Conclusions: Low p27 Kip1 expression is an independent adverse prognostic factor in patients with MM. The proposed risk score might be useful for risk-adapted treatment in the future.