Correlation of intratumoral microvessel density and p53 protein overexpression in human colorectal adenocarcinoma.
A malignant cell population needs the development of microvessels in order to grow and metastasize. Recently, a role for the p53 gene in the regulation of this angiogenic process has been suggested. Wild-type p53 is involved in the secretion of Trombospondin-1 (TSP-1), an angiogenesis inhibitor. Mutations of the p53 gene cause a downregulation of TSP-1 mRNA in cell lines. Mutant p53 also upregulates the expression of vascular endothelial cell growth factor, a potent angiogenic factor. Together with the reported association of p53 protein overexpression and microvessel density (MVD) in head-and-neck squamous-cell carcinoma, these in vitro findings led us to investigate whether this association would also apply in colorectal adenocarcinomas. Structural changes of the p53 gene are the most frequent observed mutations in colorectal carcinoma and are suspected to be involved in the carcinogenesis at a relatively early stage. Parallel tissue sections from primary colorectal adenocarcinomas were immunostained for CD31, an endothelial cell marker, and with DO7, recognizing both mutant and wild-type p53 protein overexpression. The presence of p53 protein overexpression was found to be significantly associated with high MVD in the vascular hot spots. Our results are in accordance with the in vitro studies on the involvement of p53 in angiogenesis. Mutant p53 might stimulate tumor angiogenesis both indirectly, by augmenting the tumor cell proliferation, and directly, by upregulating angiogenic factors and downregulating angiogenic inhibitors.
Vermeulen
P B
PB
Laboratory of Cancer Research and Clinical Oncology, Antwerp University (U.I.A.), Wilrijk, Belgium.
Roland
L
L
Mertens
V
V
Van Marck
E
E
De Bruijn
E A
EA
Van Oosterom
A T
AT
Dirix
L Y
LY
D000230:Adenocarcinoma / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53