Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1

作者：Kolar Z; Flavell JR; Ehrmann J; Rihakova P; Macak J; Lowe D; Crocker J; Vojtesek B; Young LS; Murray PG^*

来源：Journal of Pathology, 2000, 190(5): 604-612.

DOI：10.1002/(SICI)1096-9896(200004)190:5<604::AID-PATH561>3.0.CO;2-P

• Hodgkin's disease
• apoptosis
• DNA fragmentation
• p27KIP1
• p21WAF1/CIP1

Previous results from B-cell chronic lymphocytic leukaemia suggest that expression of p27KIP1 might be important in protection from apoptosis, Given the relevance of apoptosis to the pathogenesis of Hodgkin's disease (HD), it was decided to examine the expression of p27KIP1 in relation to apoptosis in these lesions, Paraffin-wax sections from a total of 65 histologically confirmed HD tumours mere used to derive apoptotic index (AI) and DIVA fragmentation index (DFI) scores, which mere compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), wp21WAF1/CIP1 (p21) and cyclin D1, and with Epstein-Barr virus (EBV) status. The DFI was measured by TdT-mediated dUTP-FITC nick end-labelling (TUNEL), and the AI by conventional morphology. Cells shelving the typical morphology of apoptosis, together with those resembling so-called 'mummified' Hodgkin/Reed-Sternberg (HRS) cells, were included in AI measurements, Increasing numbers of p27-positive HRS cells were associated with lo,ver levels of apoptosis in these cells, as indicated by significantly lower AI and DFI scores. There was a trend towards poorer survival in those patients with the highest numbers of p27-positive LIPS cells and with lower AI and DFI scores, but these differences mere not statistically significant, p21-positive HRS cells were significantly more frequent in those cases with lower AI scores, A similar trend was observed for p21 and DFI, although this relationship was not statistically significant. There was also a trend towards higher levels of cyclin D1 protein in HD cases with high AI and DFI values. A tendency for increasing: numbers of p27-positive and p21-positive HRS cells in EBV-positive cases was noted, but this relationship,vas not statistically significant. EBV status did not correlate with either AI or DFI scores. The results of this study suggest that p27, and possibly also p21, may be involved in protection from apoptosis in HD.

• 出版日期2000-4