Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

Michael Boe Møller, O Nielsen, Niels Tinggaard Pedersen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2002-Oct
OriginalsprogEngelsk
TidsskriftHistopathology
Vol/bind41
Udgave nummer4
Sider (fra-til)322-30
Antal sider8
ISSN0309-0167
StatusUdgivet - 1. okt. 2002

Fingeraftryk

Non-Hodgkin's Lymphoma
Lymphoma
Lymphoma, Large B-Cell, Diffuse
T-Cell Lymphoma
Cyclin D3
Marginal Zone B-Cell Lymphoma
Drug Resistance

Citer dette

@article{8df5a000de6911dd9909000ea68e967b,
title = "Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma",
abstract = "AIMS: Recurrence of non-Hodgkin's lymphoma with or without transformation is often associated with increased clinical drug resistance and poor prognosis indicating molecular progression. The study addresses the currently poorly understood molecular mechanisms underlying relapsing non-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53 alterations as 5/6 (83{\%}) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non-Hodgkin's lymphoma, as 2/5 (40{\%}) diffuse large B-cell lymphomas and 3/9 (33{\%}) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80{\%}) transformed diffuse large B-cell lymphomas developed MDM2 over-expression. CONCLUSION: Our data are consistent with the notion that p53 alterations are important for the histological transformation of follicle centre lymphoma. However, the data also suggest that relapsing follicle centre lymphomas without overt transformation often have p53 alterations and increased risk of transformation, and that relapse of de novo diffuse large B-cell lymphomas and T-cell non-Hodgkin's lymphomas is associated with p53 alterations. Furthermore, our results are consistent with an association of MDM2 over-expression with histological transformation of both follicle centre lymphoma and marginal zone B-cell lymphoma.",
keywords = "Aged, Aged, 80 and over, Cell Cycle Proteins, Cell Transformation, Neoplastic, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Cyclins, Disease Progression, Female, Genes, p53, Humans, Immunohistochemistry, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Male, Mutation, Nuclear Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Recurrence, Tumor Markers, Biological, Tumor Suppressor Proteins",
author = "M{\o}ller, {Michael Boe} and O Nielsen and Pedersen, {Niels Tinggaard}",
year = "2002",
month = "10",
day = "1",
language = "English",
volume = "41",
pages = "322--30",
journal = "Histopathology",
issn = "0309-0167",
publisher = "Wiley-Blackwell",
number = "4",

}

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma. / Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard.

I: Histopathology, Bind 41, Nr. 4, 01.10.2002, s. 322-30.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

AU - Møller, Michael Boe

AU - Nielsen, O

AU - Pedersen, Niels Tinggaard

PY - 2002/10/1

Y1 - 2002/10/1

N2 - AIMS: Recurrence of non-Hodgkin's lymphoma with or without transformation is often associated with increased clinical drug resistance and poor prognosis indicating molecular progression. The study addresses the currently poorly understood molecular mechanisms underlying relapsing non-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53 alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas developed MDM2 over-expression. CONCLUSION: Our data are consistent with the notion that p53 alterations are important for the histological transformation of follicle centre lymphoma. However, the data also suggest that relapsing follicle centre lymphomas without overt transformation often have p53 alterations and increased risk of transformation, and that relapse of de novo diffuse large B-cell lymphomas and T-cell non-Hodgkin's lymphomas is associated with p53 alterations. Furthermore, our results are consistent with an association of MDM2 over-expression with histological transformation of both follicle centre lymphoma and marginal zone B-cell lymphoma.

AB - AIMS: Recurrence of non-Hodgkin's lymphoma with or without transformation is often associated with increased clinical drug resistance and poor prognosis indicating molecular progression. The study addresses the currently poorly understood molecular mechanisms underlying relapsing non-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53 alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas developed MDM2 over-expression. CONCLUSION: Our data are consistent with the notion that p53 alterations are important for the histological transformation of follicle centre lymphoma. However, the data also suggest that relapsing follicle centre lymphomas without overt transformation often have p53 alterations and increased risk of transformation, and that relapse of de novo diffuse large B-cell lymphomas and T-cell non-Hodgkin's lymphomas is associated with p53 alterations. Furthermore, our results are consistent with an association of MDM2 over-expression with histological transformation of both follicle centre lymphoma and marginal zone B-cell lymphoma.

KW - Aged

KW - Aged, 80 and over

KW - Cell Cycle Proteins

KW - Cell Transformation, Neoplastic

KW - Cyclin-Dependent Kinase Inhibitor p21

KW - Cyclin-Dependent Kinase Inhibitor p27

KW - Cyclins

KW - Disease Progression

KW - Female

KW - Genes, p53

KW - Humans

KW - Immunohistochemistry

KW - Lymphoma, B-Cell

KW - Lymphoma, Follicular

KW - Lymphoma, Large B-Cell, Diffuse

KW - Lymphoma, Non-Hodgkin

KW - Lymphoma, T-Cell

KW - Male

KW - Mutation

KW - Nuclear Proteins

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-mdm2

KW - Recurrence

KW - Tumor Markers, Biological

KW - Tumor Suppressor Proteins

M3 - Journal article

VL - 41

SP - 322

EP - 330

JO - Histopathology

JF - Histopathology

SN - 0309-0167

IS - 4

ER -