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Clinical Evaluation of HER-2/neu Protein in Malignant Pleural Effusion-Associated Lung Adenocarcinoma and as a Tumor Marker in Pleural Effusion Diagnosis¹

Departments of Pathology [T-L. H., F-F. C.], Surgery [W-W. L.], Internal Medicine [W-T. H., W-C. S.], Radiotherapy [H. H. W. C.], Microbiology [A-L. H.], and Institute of Molecular Medicine [T-L. H., W-C. S.], National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, and Division of Cancer Research, National Health Research Institutes, Taipei 115 [J. M. L.], Taiwan

Purpose: Lung adenocarcinoma presenting as malignant pleural effusion (MPE) is common in Taiwan. Microscopically, the involved pleurae are infiltrated by numerous tumor foci, which suggests that the cancer cells are highly invasive. Overexpression of HER-2/neu has been related to proliferation, antiapoptosis, and the high invasiveness of various cancer cells. We therefore were interested in studying the role of HER-2/neu in MPE-associated adenocarcinoma cell lung cancer (ADCLC).

Experimental Design: The expression of HER-2/neu in pleural effusion was measured by ELISA. The HER-2/neu protein expression on tumor cells was evaluated by immunohistochemical (IHC) staining, and gene amplification was assayed by fluorescence in situ hybridization.

Results: The mean value of HER-2/neu in pleural effusions of patients with ADCLC and other nonmalignant lung diseases was 9.9 and 2.7 ng/ml, respectively. The difference is statistically significant (P < 0.001). Compared with cytokeratin 19 fragment CYFRA 21-1, the performance of HER-2/neu as a tumor marker in pleural effusion diagnosis was better. Overexpression of HER-2/neu in tumor tissues was found in 70% (23 of 32) of patients with MPE-associated ADCLC, 30% (13 of 43) with stage I/II non-small cell lung cancer (NSCLC), and 44% (14 of 32) with stage III NSCLC. The incidence of HER-2/neu overexpression in tumor tissues of patients with MPE-associated ADCLC was significantly higher than that of patients with stage I–III NSCLC without MPE. HER-2/neu gene amplification was uncommon (1.9%). The correlation between the IHC H-score in tumor samples and the pleural effusion level of HER-2/neu was significant (P < 0.01). A higher incidence of HER-2/neu expression beyond the cutoff point (5.5 ng/ml) in pleural effusions was also found in patients whose IHC H-scores were >50.

Conclusions: These findings indicate that HER-2/neu is important in the pathogenesis of MPE-associated ADCLC and is a potential tumor marker for a diagnosis of pleural effusion.

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