Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma.
BACKGROUND
Many studies have shown that angiogenesis plays an important role in the process of cancer development and progression. Vascular endothelial growth factor (VEGF) has a potent angiogenic activity, and cyclooxygenase-2 (COX-2) supports angiogenesis by regulated production of angiogenic factors, including VEGF. The purpose of this study was to examine the expression of VEGF in combination with COX-2 and CD34, their correlation with various clinicopathological factors, and their prognostic significance in human gastric carcinoma.


METHODS
Specimens from 169 patients with different grade and stage gastric carcinoma were investigated by immunohistochemistry for COX-2 and VEGF expression. Tumor microvessel density was assessed with CD34 immunostaining. Correlations between the expression of VEGF, COX-2, CD34, and various clinicopathological factors were studied. The effect of these proteins on patient survival was determined.


RESULTS
COX-2 and VEGF were positively expressed in 36.7% and 50.3% of the patients, respectively. Positive correlation was found between VEGF and COX-2 and between VEGF and CD34. VEGF expression was correlated with depth of invasion; metastatic lymph nodes; lymphatic and venous invasion; and tumor, node, metastasis system stage. Patients with positive staining for VEGF showed far lower disease-free (64.9% vs. 81.3%) and overall (58.3% vs. 76.9%) survival rates than VEGF-negative patients. In multivariate analysis, only tumor location, depth of invasion, and lymph node metastasis were shown to be independent prognostic factors.


CONCLUSIONS
VEGF expression correlates with angiogenesis and tumor progression and is a valuable prognostic factor in patients with gastric carcinoma.
Surgical Oncology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan. kolev.srg2@tmd.ac.jp
Yanislav
Y
Kolev
Hiroyuki
H
Uetake
Satoru
S
Iida
Toshiaki
T
Ishikawa
Tatsuyuki
T
Kawano
Kenichi
K
Sugihara
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human