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Low p27^Kip1 Expression Is an Independent Adverse Prognostic Factor in Patients with Multiple Myeloma¹

Department of Medicine I, Clinical Division of Oncology [M. F., G. P., T. S., H. K., J. A., J. D.], Division of Hematology and Blood Coagulation [H. Gi.], Bone Marrow Transplantation Unit [H. Gr.], and Department of Clinical Pathology [A. C.], University of Vienna, A-1090 Vienna, Austria

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 ß₂-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.

Commentary

Prognostic Factors in Multiple Myeloma: It’s in the Genes

P. Leif Bergsagel
Clin. Cancer Res. 2003 9: 533-534. [Full Text] [PDF]

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