Frequent Expression of the Vascular Endothelial Growth Factor in Human Non-small-cell Lung Cancers

Abstract

Background: Angiogenesis is an essential factor for progression and metastases in solid tumors. It has been reported that several angiogenic factors playa role in the regulation of angiogenesis. Vascular endothelial growth factor (VEGF) is one of the most important molecules in angiogenesis. We investigated expressions of VEGF in a series of lung carcinomas with regard to clinicopathological factors. Method: VEGF expression was investigated by use of immunohistochemical studies and Northern blot analysis, using 155 primary and 26 metastatic lung carcinomas for the immunohistochemical studies and 10 primary and two metastatic lung carcinomas for the Northern blot analysis. All lesions were resected at surgery. Results: The frequencies for positive VEGFexpression were 64 of 74 (86.5%) adenocarcinomas, 38 of 67 (56.7%) squamous cell carcinomas, four of four (100%) large cell carcinomas, two of three (66.7%) adenosquamous carcinomas and one of five (20%) small-cell carcinomas, the degree of positivity generally being greater in well differentiated tumors. The majority of metastatic foci from adenocarcinomas and squamous cell carcinomas at other sites were also positive (76.5 and 66.70/0, respectively). VEGF expression did not correlate with clinicopathological factors such as tumor size or pathological stage, but pathological stage I adenocarcinoma cases positive for VEGF demonstrated a shorter disease-free period when followed up for 48 months than those cases expressing VEGF negatively. Conclusions: The results indicated that VEGF expression was frequently detected in non-small-cell lung cancers and suggested that VEGF might relate to the disease-free period of the patients with early adenocarcinomas.

Serum angiopoietin-1 as a prognostic marker in resected early stage lung cancer

“…However, an earlier study found variable serum Ang-1 levels according to different types of cancers [25]. In tissue studies, Ang-1 is upregulated in various malignancies, with a few exceptions [22,29,38]. In lung cancer tissues, the expression pattern of Ang-1 is variable and its clinical significance is controversial [19,22,24,39].…”

“…In tissue studies, Ang-1 is upregulated in various malignancies, with a few exceptions [22,29,38]. In lung cancer tissues, the expression pattern of Ang-1 is variable and its clinical significance is controversial [19,22,24,39]. The overall contradictory findings regarding Ang-1 expression may not be explained adequately by the differences in laboratory methodologies and study populations.…”

“…Ang-2 is upregulated in various cancers, including lung cancer [22,23], and its expression is co-localized and correlated with that of VEGF [19]. The tissue expression level of Ang-2 is related to the stage progression and overall survival [23,24].…”

“…Although Ang-1 has been shown to be upregulated in many cancer tissues [22,[29][30][31], its expression was rather lower in some cancer types, including lung cancer, compared with normal tissues [19,32]. There are a few studies on serum Ang-1 levels, and these have reported conflicting results.…”

Stabilization of breast cancer xenograft tumour neovasculature by angiopoietin-1

“…It has also been reported that Ang1 as well as Ang2 were direct substrates in endothelial cell adhesion mediated by integrins (Carlson et al, 2001). Many studies have investigated the expression patterns of Ang1, other angiopoietins, and Tie2 in a variety of tumours, including cancers of the breast (Hayes et al, 2000;Currie et al, 2001), brain (Stratmann et al, 1998;Zagzag et al, 1999;Eggert et al, 2000), liver (Tanaka et al, 1999), ovary (Martoglio et al, 2000), lung (Takahama et al, 1999;Wong et al, 2000), Kaposi's sarcoma and cutaneous angiosarcoma , thyroid gland (Bunone et al, 1999), and leukaemia (Kukk et al, 1997). These studies revealed a complex pattern of expression of the angiopoietins and Tie2 that is consistent with an important role for Ang2 and VEGF in the destabilization of vasculature and initiation of tumour angiogenesis.…”