Angiogenesis and p53 expression in the colorectal adenoma-carcinoma sequence.
Angiogenesis, the formation of new vessels, is essential for tumor growth and metastasis. Mutations of p53 tumor suppressor gene are frequent and play an important role in colorectal oncogenesis. A role of p53 as an angiogenesis inhibitor has also been proposed. We evaluated angiogenesis and p53 expression in 16 hyperplastic polyps, 35 solitary tubular and tubulovillous adenomas, and 47 cases of sporadic colorectal carcinomas arising on the basis of preexisting adenomas, with standard immunohistochemical techniques. The mean microvessel density (MVD) in carcinomas was significantly higher compared with the respective adenomatous part of the same tumor (27.9 vs. 7; P=0.0001). Linear regression analysis of MVD between cancerous and adenomatous areas showed a significant correlation (P = 0.0001, r = 0.56), raising the possibility that carcinomas arising from better vascularized adenomas might show increased vascularity. The MVD was significantly higher in stage C compared with stage A cases (P=0.04). p53 positivity was detected in 26 of 47 cancerous (55%) and in 14 of 47 adenomatous areas (30%; P = 0.0002). All carcinomas arising from p53-positive adenomas were also p53 positive. p53 positivity associated with a higher MVD in adenomas (P = 0.02), but not in carcinomas (P = 0.78). We conclude that angiogenesis and p53 play a critical role in colorectal neoplasia, and the process of malignant transformation in tumors arising from highly angiogenic adenomas, particularly those carrying p53 mutations, is accelerated with rapid tumor progression from stage to stage, indicating a more aggressive tumor phenotype.
Kakolyris
S A
SA
Department of Clinical Oncology, University Hospital of Heraklion, Crete, Greece. GeorgSec@med.uch.gr
Kaklamanis
L G
LG
Koukourakis
M J
MJ
Giatromanolaki
A
A
Rousomoustakaki
M
M
Souglakos
J C
JC
Reppa
D K
DK
Georgoulias
V A
VA
Gatter
K C
KC
Harris
A L
AL
D000236:Adenoma / Q000098:blood supply / Q000378:metabolism*; D002277:Carcinoma / Q000098:blood supply / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000378:metabolism*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D009154:Mutation; D009389:Neovascularization, Pathologic; D010641:Phenotype; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D016159:Tumor Suppressor Protein p53