Overexpression of VEGF is associated with positive p53 immunostaining in hepatocellular carcinoma (HCC) and adverse outcome of HCC patients.
OBJECTIVE
To elucidate the clinicopathological correlations among vascular endothelial growth factor (VEGF), microvessel density (MVD) and tumor suppressor gene p53 in hepatocellular carcinomas (HCCs), we adopted a new definition of "VEGF overexpression."


METHODS
The expressions of VEGF, MVD, and p53 in 113 HCC specimens were analyzed by immunohistochemistry.


RESULTS
VEGF expression in surrounding liver tended to be stronger (VEGF overexpression, 31%) than, or similar to (57%) that in HCCs (P = 0.001). P53 positivity was noted in 42 cases (37.1%). MVD ranged from 22 to 201 microvessels/field determined for 5 high-power fields. VEGF expression in HCCs was positively correlated with MVD (P = 0.001). VEGF overexpression is positively correlated with young age (P = 0.008), male gender (P = 0.01), hepatitis B viremia (P = 0.013), high alpha-fetoprotein levels (P < 0.001), p53 (+) (P = 0.036), advanced-stage HCC (P = 0.015), and HCC dedifferentiation (P = 0.004). Survival analyses indicated that VEGF overexpression, high MVD, and advanced-stage HCC were independent poor prognostic factors for disease-free and overall survival.


CONCLUSIONS
This study provides evidence of a positive association between parameters reflective of angiogenesis, and p53 expression in HCCs. VEGF overexpression exhibited a significant correlation with viremia and survival.
Tseng
Po-Lin
PL
Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Tai
Ming-Hong
MH
Huang
Chao-Cheng
CC
Wang
Chih-Chi
CC
Lin
Jui-Wei
JW
Hung
Chao-Hung
CH
Chen
Chien-Hung
CH
Wang
Jing-Houng
JH
Lu
Sheng-Nan
SN
Lee
Chuan-Mo
CM
Changchien
Chi-Sin
CS
Hu
Tsung-Hui
TH
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D016158:Genes, p53 / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D012737:Sex Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D000509:alpha-Fetoproteins / Q000032:analysis
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000509:alpha-Fetoproteins