A Molecular Diagnostic Test for Distinguishing Lung Adenocarcinoma from Malignant Mesothelioma Using Cells Collected from Pleural Effusions

Clinical Cancer Research. 2006 Sep 1;12(17):5129-5135. [Link]

Andrew J. Holloway^1,2, Dileepa S. Diyagama¹, Ken Opeskin^3,4, Jenette Creaney⁵, Bruce W.S. Robinson^5,6, Richard A. Lake^5,6 and David D.L. Bowtell^1,2

Authors’ Affiliations: ¹ Ian Potter Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, East Melbourne, Departments of ² Biochemistry and Molecular Biology and ³ Pathology, University of Melbourne, Parkville, ⁴ Department of Anatomical Pathology, St. Vincent’s Hospital, Fitzroy, Victoria, ⁵ School of Medicine and Pharmacology, University of Western Australia, Crawley, and ⁶ Western Australian Institute of Medical Research, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia

Requests for reprints: Andrew J. Holloway, Ian Potter Centre for Cancer Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett Street, Melbourne, Victoria, Australia 8006. Phone: 61-3-9656-1789; Fax: 61-3-9656-1414; E-mail: andrew.holloway@petermac.org.

Abstract

Purpose: Patients with malignant mesothelioma or adenocarcinoma of the lung often present with respiratory complications associated with a malignant pleural effusion. Distinguishing between these malignancies is frequently problematic, as many of the clinical, cytologic, and histologic features of the diseases overlap. Following cytologic analysis of pleural effusions, subsequent confirmatory tissue biopsies involve increased patient morbidity and expense. We have therefore designed a gene expression–based test to classify the primary tumor causing a malignant pleural effusion, using cells collected from the effusion itself.

Experimental Design: We have used microarray data for 190 lung adenocarcinomas and 33 malignant mesotheliomas to identify genes differentially expressed between the two diseases. Genes expressed in normal mesothelial cells were removed, allowing the development of a PCR-based test to measure the expression of genes that discriminate between mesothelioma and lung adenocarcinoma from cytology specimens.

Results: Applying an real-time PCR–based assay involving 17 genes to 13 independent samples from biopsy-proven malignant mesothelioma and lung adenocarcinomas resulted in the correct identification of all samples.

Conclusions: We have developed a test that is able to distinguish between lung adenocarcinoma and mesothelioma in cells collected from pleural effusions.