Carcinogenesis Advance Access first published online on September 24, 2004
This version published online on October 11, 2004
Carcinogenesis, doi:10.1093/carcin/bgh276
© 2004 by Oxford University Press
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1 Department of Pathology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
* To whom correspondence should be addressed. E-mail: sakari.knuutila{at}helsinki.fi.
Malignant pleural mesothelioma (MM) is a rare tumour with high mortality, which can exhibit various morphologies classified as epithelioid, biphasic and sarcomatoid subtypes. To investigate the molecular changes in these tumours, we studied gene expression patterns by combined use of cDNA arrays and tumour tissue microarrays (TMA). Deregulation of the expression of 588 cancer-related genes was screened in 16 MM comprising all three subtypes and compared to references, i.e., normal mesothelial cell lines and pleural mesothelium. Array data were analysed using three statistical methods; principal component analysis (PCA), permutation test, and receiver operating characteristic (ROC) curves. Eleven genes were verified by real-time RT-PCR. Genes encoding two adhesion molecules [(COL1A2 and integrin
Revised January 26, 2004
Accepted August 27, 2004
CANCER BIOLOGY
L1CAM, INP10, P-cadherin, tPA and ITGB4 overexpression in malignant pleural mesotheliomas revealed by combined use of cDNA and tissue microarray
2 Department of Histopathology, Royal Brompton Hospital, London, UK
3 Department of Pathology, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Occupational Medicine, Finnish Institute of Occupational Health, Helsinki, Finland; Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland
4 Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland
5 Department of Occupational Medicine, Finnish Institute of Occupational Health, Helsinki, Finland; Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland
6 Department of Internal Medicine, Division of Pulmonary Diseases, Helsinki University Central Hospital, Helsinki, Finland
Abstract 
4 (ITGB4)] and a chemokine (INP10) were upregulated in MM compared with both the cell lines and pleural mesothelium. There was a type-specific upregulation of semaphorin E, ITGB4, and P-cadherin in epithelioid MM, matrix metalloproteinase 9 (MMP9) and tissue type plasminogen activator (tPA) in sarcomatoid MM and neural cell adhesion molecule L1 (L1CAM) and INP10 in biphasic MM. Immunohistochemistry on TMA containing 47 MM (26 epithelioid, 15 sarcomatoid and 6 biphasic) was performed for five proteins, ITGB4, P-cadherin, tPA, INP10, and L1CAM. INP10 expression was increased in MM in general compared with normal mesothelium, while increased expression of P-cadherin, L1CAM, and ITGB4 was more specific in MMs exhibiting an epithelioid growth pattern. The overexpression of tPA was more frequent in epithelioid MM despite higher mRNA levels in sarcomatoid and biphasic MM. We conclude that several proteins, associated with cell adhesion either directly (ITGB4, L1CAM, P-cadherin) or as a regulatory factor (INP10), are differentially expressed in MM. In particular, INP10, ITGB4 and COL1A2 were upregulated in MM compared with both reference sample types, suggesting a relationship with development of these tumours.
The originally published version of this article was incorrect. The title was incomplete. The publisher apologizes for this omission.
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