| Background and Objectives Colorcclal carcinoma is one of the most common gaslrocntcric malignant diseases. In most cases coloreclal carcinoma is believed to develop from adenoma, the so called "adenoma-carcinoma sequence". Angiogcnesis is essential for tumor growth and metastasis, and ability to induce and sustain angiogenesis is a major premise for the development of cancer. Thus, blocking vascular formation may be a promising strategy to arrest tumor growth. However, the exact time when angiogenic clones appear in coloreclal tumorigenesis remains unknown. Microvessel density (MVD) has been reported to be an independent prognostic indicator of outcome in a variety of human malignancies, but, to date, MVD has been assessed by using panendothelial markers, e.g. CD31, CD34, and factor VIII, but their expressions arc not always observed in angiogenic vessels, and such marks are not useful for measuring angiogenesis. Endoglin is a proliferation-associated antigen of cndolhclial cells (ECs) which expresses more abundantly on the vascular cndothclium of tumor tissues than that of normal tissues, and up-regulated by hypoxia. In addition, Endoglin is an ancillary transforming growth factor P (TGF- P ) receptor, and binds TGF- 1 and TGF- 3 with high affinity in human ECs. Vascular endolhclial growth factor (VEGF) has been identified as one of the most potent inducers of tumor associated angiogenesis, suggesting that itbe an important positive regulator of angiogcncsis. VEGF, a secreted glycoprotein, can expressed by normal cells and conditioned tumor cells, hypoxia can up-regulate transcription of VEGF gene. PTK/ZK, an oral potent and selective inhibitor of the VEGF receptor lyrosine kinases, phase III trails arc underway to evaluate it's efficacy. In the present study, we hypothesized that microvessel quantification with Endoglin might be a better way to evaluate the onset of angiogenesis in the colorcctal adenoma-carcinoma sequence compared with conventional pancndothelial markers. We also investigated the relationship between expression of VEGF and MVD assessed by Endoglin in colorcctal tumorigcnesis. The aim of this study was to explore popularizing Endoglin as a kind of basic marker of active vascular cndothelium and provide experimental evidence of antiangiogenic therapy by targeting VEGF and Endoglin.Methods The expressions of Endoglin, CD31 and VEGF in 10 cases of normal colorectal mucosa tissues, 45 cases of colorcctal adenomas (22 cases of mild dysplasia adenomas and 23 cases of severed dysplasia adenomas), and 41 cases of colorectal adenocarcinomas were examined by use of S-P immunohistochemistry. MVD labeled by anli-Endoglin monoclonal antibody (Mab) and anti-CD31 Mab were counted at X 200 magnification.Results (1) Microvessels positive for Endoglin were preferentially observed in the surface of adenomas and adenocarcinomas. MVD for Endoglin in normal tissues, low-grade dysplasia, high-grade dysplasia, and carcinomas was 20.29 + 8.52, 38.80 7.60, 63.62+11.84 and 71.40 + 10.32, respectively. An increment of MVD for Endoglin in adenoma-adenocarcinoma sequence was statistically significant (P<0.001) . In contrast to the expression of Endoglin, microvessels positive for CD31 distributed almost uniformly in adenoma tissues. In many cases CD31 stained only a proportion of blood vessels that were positive for Endoglin. MVD for CD31 inlow-grade dysplasia, high-grade dysplasia, and carcinomas was 58.75 14. 13. 61.97 13.52 and 65. 19 15.32, respectively. No significant differences were observed in the adenoma-carcinoma sequencc( P >0.05).(2) The positive expression rale of VEGF in normal mucosa, low-grade dysplasia, high-grade dysplasia, carcinoma without metastasis and carcinoma with metastasis was 10%, 22.7%, 43.5%, 52.6% and 72.7%, respectively. An increment expression of VEGF in adenoma-carcinoma sequence was statistically significant ( F<0.01).(3) The expression of Endoglin were positively correlated to depth of invasion, lymph-node metastasis and Dukes stage (P<0.01, /MX01 and P<0.01). Cas...
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