Malignant pleural mesothelioma and mesothelial hyperplasia: A new molecular tool for the differential diagnosis.
Malignant pleural mesothelioma (MPM) is a rare asbestos related cancer, aggressive and unresponsive to therapies. Histological examination of pleural lesions is the gold standard of MPM diagnosis, although it is sometimes hard to discriminate the epithelioid type of MPM from benign mesothelial hyperplasia (MH).This work aims to define a new molecular tool for the differential diagnosis of MPM, using the expression profile of 117 genes deregulated in this tumour.The gene expression analysis was performed by nanoString System on tumour tissues from 36 epithelioid MPM and 17 MH patients, and on 14 mesothelial pleural samples analysed in a blind way. Data analysis included raw nanoString data normalization, unsupervised cluster analysis by Pearson correlation, non-parametric Mann Whitney U-test and molecular classification by the Uncorrelated Shrunken Centroid (USC) Algorithm.The Mann-Whitney U-test found 35 genes upregulated and 31 downregulated in MPM. The unsupervised cluster analysis revealed two clusters, one composed only of MPM and one only of MH samples, thus revealing class-specific gene profiles. The Uncorrelated Shrunken Centroid algorithm identified two classifiers, one including 22 genes and the other 40 genes, able to properly classify all the samples as benign or malignant using gene expression data; both classifiers were also able to correctly determine, in a blind analysis, the diagnostic categories of all the 14 unknown samples.In conclusion we delineated a diagnostic tool combining molecular data (gene expression) and computational analysis (USC algorithm), which can be applied in the clinical practice for the differential diagnosis of MPM.
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
Rossella
R
Bruno
Division of Pathological Anatomy, University Hospital of Pisa, Pisa, Italy.
Greta
G
Alì
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.
Riccardo
R
Giannini
Division of Pathological Anatomy, University Hospital of Pisa, Pisa, Italy.
Agnese
A
Proietti
Division of Thoracic Surgery, University Hospital of Pisa, Pisa, Italy.
Marco
M
Lucchi
Division of Pneumology, University Hospital of Pisa, Pisa, Italy.
Antonio
A
Chella
Division of Thoracic Surgery, University Hospital of Pisa, Pisa, Italy.
Franca
F
Melfi
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.|Division of Thoracic Surgery, University Hospital of Pisa, Pisa, Italy.
Alfredo
A
Mussi
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy.|Program of Pleuropulmonary Pathology, University Hospital of Pisa, Pisa, Italy.
Gabriella
G
Fontanini
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000235:genetics*; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor
classification models; differential diagnosis; gene profiles; malignant pleural mesothelioma; mesothelial hyperplasia