Protein Expression of Cell Cycle Regulator, p27Kip1, Correlates with Histopathological Grade of Non‐Hodgkin's Lymphoma

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Abstract
The protein p27Kp1 is one of the cyclin‐dependent kinase inhibitors that are known to play important roles in the regulation of cell‐cycle progression. Low levels of p27 expression in malignant cells are associated with poor prognosis in patients with breast, lung, colorectal and gastric cancers. To determine the relation of cyclin‐dependent kinase inhibitors to histopathological grades of B‐cell non‐Hodgkin's lymphomas, the expression of p27, cyclin D1 and cyclin E in lymph node tissues was investigated in 56 patients with B‐cell non‐Hodgkin's lymphomas by western blotting and immunohistochemical techniques. High levels of p27 expression were observed in most lymph node tissue samples (93%) obtained from patients with low grade B‐cell non‐Hodgkin's lymphomas, while expression was low in lymph node tissue taken from all patients with intermediate and high grade B‐cell non‐Hodgkin's lymphomas. The difference in p27 expression in lymphoma tissues was significant among the different histopathological grades of B‐cell non‐Hodgkin's lymphomas (P<0.01). The analysis of the survival time of patients showed that the reduction of p27 expression correlated with poor prognosis. Cyclin D1, showed a high level of expression in mantle cell lymphomas and high grade B‐cell non‐Hodgkin's lymphomas. Cyclin E showed limited expression in 18 of 31 lymphoma tissues. Both cyclin D1 and E protein expression were not significantly different among the grades of B‐cell non‐Hodgkin's lymphomas. These results demonstrate that the level of p27 expression in lymphoma tissue is an important parameter in the classification of B‐cell non‐Hodgkin's lymphomas and in the prediction of prognosis.