title: [Epidermal growth factor receptor aberrations in malignant mesotheliomas].
abstract: Recently, the incidence of malignant mesothelioma has been increasing from such causes as asbestos exposure. In this study, we compared Epidermal Growth Factor Receptor (EGFR) aberrations in malignant mesotheliomas to those in lung cancers, to determine whether gefitinib may be useful for treatment of a malignant mesothelioma. We investigated 15 cases with malignant mesothelioma, 5 with lung cancer, and 10 with cell block from pleural effusion. In the malignant mesothelioma and lung cancer cases, we also examined the expression of EGFR by immunostaining using two kinds of anti-EGFR antibodies. In addition, we searched for ser473 p-Akt (p-Akt), which is activated by EGFR, and Epithelial Membrane Antigen (EMA), which is generally used as differential diagnosis marker of mesothelial cells. Furthermore, we examined the expressions of EGFR and EMA in benign mesothelial cells in cell blocks. Numerical abnormalities of the EGFR gene were examined by chromosome in situ hybridization, while the exonl9 and exon21 gene mutations of EGFR were examined using PCR-heteroduplex and PCR-RFLP methods, respectively. Our results showed that the EGFR protein was expressed in most of the malignant mesotheliomas in the same manner as in the lung cancer specimens. On the other hand, p-Akt was expressed in all cases (100%) of lung cancer, whereas that expression was seen in only 1 of 15 (7%) of malignant mesothelioma cases. As for EGFR gene abnormalities, a mutation was found in 1 (20%) and gene amplification in 2 (40%) lung cancer cases, while in malignant mesothelioma cases, amplification was found in 2 cases (13%) and no mutation was detected in any. Moreover, in staining results with one of the antibodies, the expression of EGFR was not different between malignant mesothelioma and non-neoplastic mesothelial cells. We observed EGFR expression at a high frequency in both the malignant mesothelioma and lung cancer specimens. However, distinct differences were detected between them in regard to EGFR gene abnormalities and the expression of p-Akt. These results suggest that it would be rare for a patient with malignant mesothelioma to benefit from gefitinib treatment.
authors.affiliation: Department of Pathology, Tsuchiura Kyodo General Hospital, Tsuchiura 300-0053, Japan. isohama2587@proof.ocn.ne.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takabe
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry; D008654:Mesothelioma / Q000737:chemistry* / Q000188:drug therapy; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib