Low p27Kip1 expression is an independent adverse prognostic factor in patients with multiple myeloma.
OBJECTIVE
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.


METHODS
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 beta(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.
Filipits
Martin
M
Department of Medicine I, Clinical Division of Oncology, University of Vienna, A-1090 Vienna, Austria. martin.filipits@akh-wein.ac.at
Pohl
Gudrun
G
Stranzl
Thomas
T
Kaufmann
Hannes
H
Ackermann
Jutta
J
Gisslinger
Heinz
H
Greinix
Hildegard
H
Chott
Andreas
A
Drach
Johannes
J
D000328:Adult; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27