Guo JianFei, Higashi Kotaro, Ueda Yoshimichi, Oguchi Manabu, Takegami Tsutomu, Toga Hirohisa, Sakuma Tsutomu, Yokota Hajime, Katsuda Shogo, Tonami Hisao, Yamamoto Itaru
Department of Radiology, Kanazawa Medical University, Ishikawa, Japan.
J Nucl Med. 2006 Mar;47(3):419-25.
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.
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/alpha-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.
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).
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.
尽管已经研究多年，但微血管密度（MVD）所反映的肿瘤血管生成的预后价值仍存在争议，且此前尚无关于肺腺癌中MVD与18F-FDG摄取相关性的报道。因此，在本研究中，我们调查了用不同内皮细胞抗体测定的MVD与18F-FDG摄取之间的相关性，并比较了这些因素对肺腺癌预后的影响。
44例患有45个肺腺癌的患者在手术前行18F-FDG PET检查。从每个切除的肿瘤中获取的连续石蜡包埋切片进行CD31（一种全内皮细胞标志物）、CD105（一种与增殖相关的内皮细胞标志物）和CD34/α-SMA（用于内皮细胞和平滑肌细胞双重标记）免疫染色。选择MVD最高区域的四个高倍视野进行分析。采用计算机辅助图像分析评估MVD。
全内皮细胞标志物的MVD染色结果可分为3种微血管模式：弥漫型、肺泡型和混合型。高度有序的肺泡型模式被认为代表被困在肺腺癌中的原有肺泡血管，可能对肿瘤的侵袭性无显著意义。原有肺泡细胞也对18F-FDG摄取无贡献。MVD的CD105染色（CD105-MVD）与18F-FDG摄取呈显著正相关（P<0.0001），而MVD的CD31染色（CD31-MVD）与之呈微弱负相关（P=0.057）。尽管CD105-MVD与预后呈负相关，但在无病生存分析和总生存分析中，CD105-MVD低的患者与CD105-MVD高或中等的患者相比，预后要好得多（分别为P=0.017和P=0.013）。CD31-MVD低的患者预后最差（无病生存分析中P=0.032，总生存分析中P=0.179）。
18F-FDG摄取与用全内皮细胞标志物（CD31和CD34）测定的MVD之间无正相关；相反，它们之间存在微弱负相关。用与增殖相关的内皮细胞标志物CD105测定的MVD反映了活跃的血管生成，与18F-FDG摄取呈正相关，是肺腺癌预后的更好指标。
