p27KIP1 is abnormally expressed in Diffuse Large B-Cell Lymphomas and is associated with an adverse clinical outcome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-06-11

AUTHORS

Al Sáez, E Sánchez, M Sánchez-Beato, M A Cruz, I Chacón, E Muñoz, F I Camacho, J C Martínez-Montero, M Mollejo, J F Garcia, M A Piris

ABSTRACT

Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27KIP1 staining. We analysed p27KIP1 expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free survival (DFS) and overall survival (OS). The relationships between p27KIP1 and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27KIP1 was found in lymphomas of this type. The overall correlation between p27KIP1 and MIB-1 showed there to be no significant relationship between these two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings showed that a high level of p27KIP1 expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27KIP1 expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27KIP1 protein may be rendered non-functional through interaction with other cell cycle regulator proteins. More... »

PAGES

1427-1434

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6690539

DOI

http://dx.doi.org/10.1038/sj.bjc.6690539

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014888735

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10424746


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27 schema:description Cell cycle progression is regulated by the combined action of cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors (CDKi), which are negative cell cycle regulators. p27KIP1 is a CDKi key in cell cycle regulation, whose degradation is required for G1/S transition. In spite of the absence of p27KIP1 expression in proliferating lymphocytes, some aggressive B-cell lymphomas have been reported to show an anomalous p27KIP1 staining. We analysed p27KIP1 expression in a series of Diffuse Large B-cell Lymphoma (DLBCL), correlating it with the proliferative index and clinical outcome, to characterize the implications of this anomalous staining in lymphomagenesis in greater depth. For the above mentioned purposes, an immunohistochemical technique in paraffin-embedded tissues was employed, using commercially available antibodies, in a series of 133 patients with known clinical outcomes. Statistical analysis was performed in order to ascertain which clinical and molecular variables may influence outcome, in terms of disease-free survival (DFS) and overall survival (OS). The relationships between p27KIP1 and MIB-1 (Ki-67) were also tested. An abnormally high expression of p27KIP1 was found in lymphomas of this type. The overall correlation between p27KIP1 and MIB-1 showed there to be no significant relationship between these two parameters, this differing from observations in reactive lymphoid and other tissues. Analysis of the clinical relevance of these findings showed that a high level of p27KIP1 expression in this type of tumour is an adverse prognostic marker, in both univariate and multivariate analysis. These results show that there is abnormal p27KIP1 expression in DLBCL, with adverse clinical significance, suggesting that this anomalous p27KIP1 protein may be rendered non-functional through interaction with other cell cycle regulator proteins.
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35 CDKi key
36 DLBCL
37 Diffuse Large B
38 G1/S transition
39 Large B
40 MIB-1
41 S transition
42 abnormal p27KIP1 expression
43 absence
44 action
45 action of cyclins
46 adverse clinical outcomes
47 adverse clinical significance
48 adverse prognostic marker
49 analysis
50 anomalous p27KIP1 protein
51 anomalous p27KIP1 staining
52 anomalous staining
53 antibodies
54 available antibodies
55 cell cycle progression
56 cell cycle regulation
57 cell cycle regulator proteins
58 cell cycle regulators
59 cell lymphoma
60 clinical outcomes
61 clinical relevance
62 clinical significance
63 correlation
64 cycle progression
65 cycle regulation
66 cycle regulator proteins
67 cycle regulators
68 cyclin
69 cyclin-dependent kinases
70 degradation
71 depth
72 disease-free survival
73 expression
74 findings
75 greater depth
76 high expression
77 high levels
78 immunohistochemical techniques
79 implications
80 index
81 interaction
82 key
83 kinase
84 levels
85 lymphocytes
86 lymphoid
87 lymphoma
88 lymphomagenesis
89 markers
90 molecular variables
91 negative cell cycle regulators
92 observations
93 order
94 outcomes
95 overall correlation
96 overall survival
97 p27Kip1
98 p27Kip1 expression
99 p27Kip1 protein
100 p27Kip1 staining
101 paraffin
102 parameters
103 patients
104 prognostic marker
105 progression
106 proliferative index
107 protein
108 purpose
109 reactive lymphoid
110 regulation
111 regulator
112 regulator protein
113 relationship
114 relevance
115 results
116 series
117 significance
118 significant relationship
119 spite
120 staining
121 statistical analysis
122 survival
123 technique
124 terms
125 tissue
126 transition
127 tumors
128 types
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