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Expression of CD44 Variant Exon 6 in Stage I Non-Small Cell Lung Carcinoma as a Prognostic Factor

Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University, Kyoto 606 [T. H., T. F., S. H., H. W.], and Second Department of Pathology, Fukui Medical College, Fukui 910-11 [H. N.], Japan

Specific CD44 isoforms are the surface adhesion molecules that have been shown to be associated with metastasis. In the present study, the role of the expression of standard and variant CD44 isoform (CD44s and CD44v6) as prognostic indicators in pathological stage I non-small cell lung carcinoma was investigated immunohistologically using monoclonal antibodies. The results showed that the expression of CD44v6 correlates with adverse prognosis in stage I non-small cell lung carcinoma but not CD44s. The 5-year survival rate of the patients with CD44v6-positive tumors was 50%, which was significantly lower than that of CD44v6-negative patients (88%; P = 0.001). The incidence of recurrent distant metastasis in the CD44v6-positive patients (45%; 9 of 20 patients) was significantly higher than that in the CD44v6-negative patients (20%; 10 of 49 patients; P = 0.038), suggesting the involvement of CD44v6 in hematogeneous metastasis of lung carcinoma. Although the incidence of the expression of CD44v6 in squamous cell carcinoma was significantly higher than that in adenocarcinoma, histological type was not a significant prognostic factor. No significant correlation was found between the expression of CD44v6 and lymphatic or vascular vessel invasion, although lymphatic vessel invasion was found to be an independent prognostic factor in the multivariate analysis. To investigate the relationship between the expression of CD44v6 and proliferative activity of tumor cells, the expression of proliferating cell nuclear antigen (PCNA) was examined. The expression of CD44v6 was more frequently observed in PCNA-positive patients than in PCNA-negative patients (P = 0.019), but the expression of PCNA was not a statistically significant prognostic indicator. The results of multivariate analysis by the Cox proportional hazards model showed that CD44v6 was an independent prognostic indicator. We concluded that the expression of CD44v6 is a useful prognostic factor in stage I non-small cell lung carcinoma.

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Received 11/21/97. Accepted 1/29/98.

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