Clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer.
BACKGROUND
Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1alpha (HIF-1alpha), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.We immunohistochemically assessed the HIF-1alpha, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).


RESULTS
The positive rates of p53 and HIF-1alpha (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1alpha were correlated positively with the depth of invasion (P = 0.015, P = 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (P = 0.010, P = 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (> or = 60 years old) and the intestinal type (P = 0.013, P = 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1alpha, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1alpha was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002).


CONCLUSIONS
p53, HIF-1alpha and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1alpha expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.
Oh
Sung Yong
SY
Department of Internal Medicine, Dong-A University College of Medicine, Busan, Republic of Korea. drosy@freechal.com
Kwon
Hyuk-Chan
HC
Kim
Sung-Hyun
SH
Jang
Jin Seok
JS
Kim
Min Chan
MC
Kim
Kyeong Hee
KH
Han
Jin-Yeong
JY
Kim
Chung Ock
CO
Kim
Su-Jin
SJ
Jeong
Jin-sook
JS
Kim
Hyo-Jin
HJ
D000230:Adenocarcinoma / Q000097:blood* / Q000098:blood supply / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000473:pathology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000097:blood* / Q000098:blood supply / Q000473:pathology / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000097:blood*
D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A