Correlation between apoptotic index and angiogenesis in non-small cell lung cancer: comparison between CD105 and CD34 as a marker of angiogenesis.

Only a few clinical studies have documented a significant correlation between intratumoral microvessel density (IMVD), a measurement of angiogenesis, and apoptotic index (AI), an incidence of apoptosis, although many experimental studies have confirmed that insufficient angiogenesis induces accelerated apoptotic cell death. In the present study, therefore, to assess AI in correlation with IMVD in resected non-small cell lung cancer, a total of 236 patients with pathologic stage I to IIIa were reviewed. IMVDs were determined immunohistochemically with an antibody against a pan-endothelial marker, CD34 (CD34-IMVD), and an antibody against a proliferation-related endothelial marker, CD105 (CD105-IMVD). AI was defined as the number of tumor cells positive for the terminal deoxynucleotidyl tranferase-mediated dUTP-biotin nick end-labeling staining per 1000 tumor cells. When CD34 was used as a marker of angiogenesis, the mean AIs for the lower-IMVD and the higher-IMVD patients were 20.1 and 17.5, respectively, demonstrating no significant difference between the lower- and the higher-IMVD patients. In contrast, when CD105 was used, the mean AI for the lower-IMVD patients was significantly higher than that for the higher-IMVD patients (22.0 and 15.6, respectively; P=0.019). There was no significant correlation between proliferative activity and CD34-IMVD or CD105-IMVD. These results demonstrated that that decreased angiogenesis may induce enhanced apoptotic tumor-cell death without affecting cell proliferation.