Multiple Myeloma is a plasma cell neoplasm characterized by the proliferation of monoclonal plasma cells in the bone marrow, associated with the synthesis of a monoclonal protein, either complete or incomplete (light chains only), These neoplastic plasma cells evolve from B lymphocytes. Multiple Myeloma accounts 1% of all malignant tumors and 10% of hematologic malignancies, but it is the second most common haematological malignancies. The median age for diagnosis is 69 years for males and 71 years for females.
Regarding the Ki67 is a the prototypic cell cycle related nuclear protein, expressed by proliferating cells in all phases of the active cell cycle (G1, S, G2 and M phase). It is absent in resting (G0) cells.The presence of the Ki-67 antigen is strictly associated with the cell cycle and confined to the nucleus, suggesting an important role of this structure in the maintenance and/or regulation of the cell division cycle. Regarding the p53 is a tumor suppressor gene and mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation. Aims of the study: - To find if there is any correlation between the expression of p53 and Ki67 with the stage of the disease and if there is a correlation between expression of p53 and expression of Ki67. Patients, Materials and Methods:Thirty patients with MM, in this retrospective study all formalin fixed paraffin embedded tissue were retrieved from archive files of Department of Pathology of Al- Kadhimia Hospital, Al- Yarmouk center for blood disorders, the laboratories of Al-Yarmouk hospital, the teaching laboratory of Medical city and from many private laboratories, Like Dr. Raji Al-Hadithi Lab., The private lab. of Dr. Saad Shawqi and the private lab of my supervisor Dr. Raad Al-Ani, for the period between Jan. 2004 to Aug. 2006. The immunohistochemical expression of p53 and Ki67 in the bone marrow of MM patients were investigated using Monoclonal Mouse
Anti-Human p53 Protein and Monoclonal Mouse Anti-Human Ki-67 Antigen respectively. Results and Discussion: - Multiple Myeloma cases: include 30 cases of previously diagnosed MM cases by a specialized haematologist. , 21 men (age: 40- 82 years, mean: 67) and 9 women (age: 40- 83, median: 64) were enrolled in our study. The age range was 40- 83 years. The mean age was (69.23+7.44) years old. There were 21 males (70 %) and 9 females (30 %). According to Salmon Durie staging system cases there were 11
cases (37 %) stage I, 11 cases (37 %) stage II and 8 cases (26 %) stage III. It was obvious that the highest frequency of expression of Ki67 and p53 in our immunohistochemical study lies in stage III, in which all cases
were positive for p53. While only approximately half of the cases (55 %) were positive for p53 in both stage II and stage III. P53 expression was significantly higher in stage III than stage I (p-value = 0.01; t-test). P53 expression was significantly higher in stage III than in stage II (pvalue <0.001; t-test). The p53 expression was highly significant with (r= 0.62, p <0.001); indicating an increment in p53 expression with advancing stage.The distribution of Ki67 positive cases in different stages of disease shows that the highest frequency of expression lies in stage III, in which all cases are positive for Ki67. While only seven (7) cases out of (11) (63 %) are positive for Ki67 in stage I and eight (8) cases out of (11) (72 %) are positive for Ki67 in stage II. The Ki67 expression was significantly higher in stage II than stage I (p-value = 0.011; t-test). Ki67 expression was significantly higher in stage III than in stage I (p-value <0.001; t-test) and also significantly higher than in stage II (p-value <0.001; t-test). By comparing the Ki67 expression in different stages of the disease; there was a highly significant difference (p-value <0.001). The Ki67 expression was highly significant with (r= 0.68, p <0.001); indicating an increment in Ki67 expression with advancing stage.
There is positive correlation between p53 expression and Ki67 expression (r=0.68, p <0.001). There was no significant difference in the mean p53 expression among age groups of multiple myeloma patients.There was no significant difference in the mean Ki67 expression among age groups of multiple myeloma patients.
Conclusions:-There was an increment in p53 and Ki67 expression with advanced stage of multiple myeloma, with a positive correlation between the two markers with advanced stage of the disease.