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

Previous results from B-cell chronic lymphocytic leukaemia suggest that exp ression of p27KIP1 might be important in protection from apoptosis, Given t he 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 c onfirmed HD tumours mere used to derive apoptotic index (AI) and DIVA fragm entation index (DFI) scores, which mere compared with the expression of var ious 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 apopto sis, together with those resembling so-called 'mummified' Hodgkin/Reed-Ster nberg (HRS) cells, were included in AI measurements, Increasing numbers of p27-positive HRS cells were associated with lo,ver levels of apoptosis in t hese cells, as indicated by significantly lower AI and DFI scores. There wa s a trend towards poorer survival in those patients with the highest number s of p27-positive LIPS cells and with lower AI and DFI scores, but these di fferences mere not statistically significant, p21-positive HRS cells were s ignificantly more frequent in those cases with lower AI scores, A similar t rend was observed for p21 and DFI, although this relationship was not stati stically significant. There was also a trend towards higher levels of cycli n D1 protein in HD cases with high AI and DFI values. A tendency for increa sing: numbers of p27-positive and p21-positive HRS cells in EBV-positive ca ses 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 protecti on from apoptosis in HD. Copyright (C) 2000 John Wiley & Sons, Ltd.