CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure

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http://hdl.handle.net/10138/303896

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Kettunen , E , Savukoski , S , Salmenkivi , K , Böhling , T , Vanhala , E , Kuosma , E , Anttila , S & Wolff , H 2019 , ' CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure ' , BMC Cancer , vol. 19 , 507 . https://doi.org/10.1186/s12885-019-5652-y

Title: CDKN2A copy number and p16 expression in malignant pleural mesothelioma in relation to asbestos exposure
Author: Kettunen, Eeva; Savukoski, Sauli; Salmenkivi, Kaisa; Böhling, Tom; Vanhala, Esa; Kuosma, Eeva; Anttila, Sisko; Wolff, Henrik
Contributor: University of Helsinki, HUSLAB
University of Helsinki, HUSLAB
University of Helsinki, Department of Pathology
Date: 2019-05-28
Language: eng
Number of pages: 10
Belongs to series: BMC Cancer
ISSN: 1471-2407
URI: http://hdl.handle.net/10138/303896
Abstract: BackgroundDeletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients' asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient's asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear.MethodsWe studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH.ResultsWe were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (>1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure ( 0.5 million f/g) (51.4% vs 16.7%; p=0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p=0.044, Fisher's Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen.ConclusionsWe found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.
Subject: Malignant pleural mesothelioma
CDKN2A
p16
Tumor stroma
Asbestos exposure
IN-SITU HYBRIDIZATION
HOMOZYGOUS DELETION
P16/CDKN2A DELETION
GENOMIC ALTERATIONS
PROGNOSTIC-FACTORS
TUMOR-SUPPRESSOR
9P21 DELETION
DIAGNOSIS
GENE
LUNG
3122 Cancers
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