Clinical Significance of p53, MDM2 and Cyclin D1 Protein Expression in Patients with Multiple Myeloma / 대한혈액학회지

ABSTRACT

BACKGROUND: Dysregulation of cell proliferation contributes to the pathogenesis of multiple myeloma (MM) and the number of S phase plasma cells is known to be one of the most important prognostic factors in MM. We analysed the cell cycle progression in MM using the expression of G1/S phase cell cycle regulators, such as p53, murine double minutes (MDM2) and cyclin D1. METHODS: The expressions of p53, MDM2 and cyclin D1 were evaluated by immunohistochemical staining with monoclonal antibodies, using bone marrow sections obtained from 48 patients with MM and 20 normal controls. RESULTS: The expressions of p53, MDM2 and cyclin D1 were demonstrated in 17 (35.4 %), 40 (83.3%) and 28 (58.3%) of 48 patients with MM, respectively. The expressions of cyclin D1 and p53 were positively correlated each other (P<0.05). However, no significant difference in MDM2 expression was found between the cyclin D1-positive and -negative groups. All of the control group showed negative expression. The expression of cyclin D1 and p53 in patients with MM correlated well with clinical and histologic stages (P<0.05). Even if MDM2 was upregulated in most patients with MM, no correlation was found with clinical or histologic stages. Serum beta2-microglobulin levels were reversely correlated with p53 expression, not with MDM2 or cyclin D1. After chemotherapy, all 5 patients with objective response showed decreased staining of these three proteins, comparing 10 of 13 patients with partial response or treatment failure showed no change or an increased degree of staining. No differences were observed in the survival rates between the groups with and without expression of each three proteins. CONCLUSIONS: These findings suggest that the expression of p53, MDM2 and cyclin D1 was increased in patients with MM and the expression rates of p53 and cyclin D1 were increased with the progression of the clinical and histological stages. It is considered that the detection of cell cycle regulatory proteins are important for understanding the biology of the malignant plasma cells, monitoring the results of treatment and determining the prognosis in MM.