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

2.50
Hdl Handle:
http://hdl.handle.net/2436/15815
Title:
Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1.
Authors:
Kolar, Zdenek; Flavell, Joanne R.; Ehrmann, Jiri; Rihakova, Petra; Macak, Jirka; Lowe, Derek; Crocker, John; Vojtesek, Borivoj; Young, Lawrence S.; Murray, Paul G.
Abstract:
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 were used to derive apoptotic index (AI) and DNA fragmentation index (DFI) scores, which were compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), p21WAF1/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 showing 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 lower 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 HRS cells and with lower AI and DFI scores, but these differences were 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 was 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.
Citation:
The Journal of Pathology, 190(5): 604-612
Publisher:
John Wiley And Sons
Issue Date:
2000
URI:
http://hdl.handle.net/2436/15815
DOI:
10.1002/(SICI)1096-9896(200004)190:5<604::AID-PATH561>3.0.CO;2-P
PubMed ID:
10727987
Additional Links:
http://www3.interscience.wiley.com/journal/1130/home
Type:
Article
Language:
en
Description:
Metadata only
ISSN:
0022-3417
Appears in Collections:
Cancer Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorKolar, Zdenek-
dc.contributor.authorFlavell, Joanne R.-
dc.contributor.authorEhrmann, Jiri-
dc.contributor.authorRihakova, Petra-
dc.contributor.authorMacak, Jirka-
dc.contributor.authorLowe, Derek-
dc.contributor.authorCrocker, John-
dc.contributor.authorVojtesek, Borivoj-
dc.contributor.authorYoung, Lawrence S.-
dc.contributor.authorMurray, Paul G.-
dc.date.accessioned2008-01-08T11:57:42Z-
dc.date.available2008-01-08T11:57:42Z-
dc.date.issued2000-
dc.identifier.citationThe Journal of Pathology, 190(5): 604-612en
dc.identifier.issn0022-3417-
dc.identifier.pmid10727987-
dc.identifier.doi10.1002/(SICI)1096-9896(200004)190:5<604::AID-PATH561>3.0.CO;2-P-
dc.identifier.urihttp://hdl.handle.net/2436/15815-
dc.descriptionMetadata onlyen
dc.description.abstractPrevious 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 were used to derive apoptotic index (AI) and DNA fragmentation index (DFI) scores, which were compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), p21WAF1/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 showing 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 lower 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 HRS cells and with lower AI and DFI scores, but these differences were 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 was 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.en
dc.language.isoenen
dc.publisherJohn Wiley And Sonsen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/1130/homeen
dc.subjectHodgkin's Diseaseen
dc.subjectApoptosisen
dc.subjectDNA fragmentationen
dc.subjectp27KIP1en
dc.subjectp21WAF1/CIP1en
dc.titleApoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1.en
dc.typeArticleen
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