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Microvessel Density: Correlation with ¹⁸F-FDG Uptake and Prognostic Impact in Lung Adenocarcinomas

¹ Department of Radiology, Kanazawa Medical University, Ishikawa, Japan; ² Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, People's Republic of China; ³ Department of Pathology, Kanazawa Medical University, Ishikawa, Japan; ⁴ Department of Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan; ⁵ Division of Respiratory Disease, Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan; and ⁶ Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa, Japan

Correspondence: For correspondence or reprints contact: Kotaro Higashi, MD, Department of Radiology, Kanazawa Medical University, 1-1, Daigaku, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan. E-mail: h550208{at}kanazawa-med.ac.jp

Although researched for many years, the prognostic value of tumor angiogenesis reflected by microvessel density (MVD) is still controversial, and there have been no previous reports regarding the correlation with ¹⁸F-FDG uptake in lung adenocarcinomas. Therefore, in the present study, we investigated the correlation between MVD determined with different endothelial cell antibodies and ¹⁸F-FDG uptake and compared the prognostic impact of those factors in lung adenocarcinomas. Methods: Forty-four patients with 45 lung adenocarcinomas underwent ¹⁸F-FDG PET before surgery. Consecutive paraffin-embedded sections obtained from each resected tumor were immunostained for CD31 (a panendothelial cell marker), CD105 (a proliferation-related endothelial cell marker), and CD34/-SMA (for double labeling of endothelial cells and mural cells). Four high-power fields in the area with the highest MVD were selected for analysis. Computer-assisted image analysis was used to assess MVD. Results: MVD staining results for panendothelial cell markers can be classified into 3 microvessel patterns: diffuse, alveolar, and mixed. The highly ordered alveolar pattern is believed to represent preexisting alveolar vessels trapped in lung adenocarcinomas and may have no significant meaning for the aggressiveness of tumors. Preexisting alveolar cells also do not contribute to ¹⁸F-FDG uptake. CD105 staining of MVD (CD105-MVD) showed a significantly positive correlation with ¹⁸F-FDG uptake (P < 0.0001), whereas CD31 staining of MVD (CD31-MVD) showed a marginally negative correlation with it (P = 0.057). Although CD105-MVD correlated negatively with prognosis, patients with low CD105-MVD, compared with those with high or moderate CD105-MVD, had a much better prognosis in both disease-free and overall survival analyses (P = 0.017 and P = 0.013, respectively). Patients with low CD31-MVD had the worst prognosis (P = 0.032 for disease-free survival analysis and P = 0.179 for overall survival analysis). Conclusion: There is no positive correlation between ¹⁸F-FDG uptake and MVD determined with panendothelial cell markers (CD31 and CD34); in contrast, there is a marginally negative correlation between them. MVD determined with CD105, which is a proliferation-related endothelial cell marker, reflects active angiogenesis, correlates positively with ¹⁸F-FDG uptake, and is a better indicator of prognosis in lung adenocarcinomas.

Key Words: PET • ¹⁸F-FDG • lung cancer • microvessel density • prognosis

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