Tumor angiogenesis is important for the progression of
cancer and is orchestrated by various factors associated with
tumor vessels,
tumor cells, and stromal cells. Angiogenic signaling in
non-small cell lung cancer (NSCLC) needs to be further clarified, especially regarding existing and upcoming therapeutic approaches. Expression of CD34, CD105, Mel-CAM,
VE-cadherin, D2-40,
VEGF, VEGFR1, and VEGFR2 was assessed immunohistochemically on a cohort of 371 well documented, surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical data and a postoperative follow-up period of up to 18 years allowed us to assess clinicopathological correlations in detail. Microvasculature in NSCLC was significantly denser at the
tumor periphery as compared to the
tumor center.
Squamous cell carcinomas (SCC) were associated with a notably lower microvessel density (MVD) than
adenocarcinomas (ACA). CD105 was present at significantly higher levels on stromal cells of ACA as compared to SCC. Expression of
VE-cadherin by
tumor cells (6% of cases, mainly ACA) as well as decreased MVD in the
tumor centers was independently associated with poor prognosis in the entire cohort. Low MVD in SCC might be related to lower efficacy of and fatal
bleeding during
therapy with
bevacizumab. In other NSCLC entities for which treatment with
VEGF inhibitors is studied in clinical trials, the predictive value of MVD for
therapy response merits to be prospectively examined. Our data suggest that patients with ACA may be candidates for
therapies targeting CD105.
VE-cadherin is another promising target for
therapy, but its expression also provides independent prognostic information.