Abstract
Background
Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. Additionally, CD-105 (endoglin) was proposed as a marker of neovascularization in solid malignancies. The aim of the present study was to (1) evaluate the VEGF and CD-105 expression in gastric carcinoma, (2) determine the role of VEGF gene sequence variations in VEGF expression in gastric carcinoma, and (3) correlate the results of VEGF and CD-105 expression with other standard prognostic parameters, such as size, grade, stage of the disease, metastases, and patient survival.
Methods
VEGF and CD-105 expression were evaluated in 100 unrelated gastric cancer patients using immunohistochemistry. For the genotyping, DNA was isolated from the blood of the gastric cancer patients and from 100 healthy individuals. The genotyping was performed by polymerase chain–restriction fragment length polymorphism analysis.
Results
VEGF protein was strongly expressed in the cytoplasm of 36% of the gastric carcinoma samples tested. In all cases, high VEGF expression was accompanied with high endoglin expression. Our results revealed no statistical significant association of any VEGF gene polymorphism with the VEGF and endoglin expression. The correlation of VEGF/CD-105 expression with the clinicopathological parameters of gastric cancer showed that the high expression of VEGF/CD015 was correlated only with lymph node metastasis (P = 0.028). The Kaplan-Meier survival curves have shown a clear association of overall survival after diagnosis of gastric cancer with high VEGF, as well as high CD-105 expression.
Conclusion
Our results support that VEGF and CD-105 are closely relevant to lymph node metastasis and act as two valuable indicators of prognosis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
P Carmeliet RK Jain (2000) ArticleTitleAngiogenesis in cancer and other diseases Nature 407 249–57 Occurrence Handle11001068 Occurrence Handle10.1038/35025220 Occurrence Handle1:CAS:528:DC%2BD3cXmvVSls74%3D
RT Poon ST Fan J Wong (2001) ArticleTitleClinical implications of circulating angiogenic factors in cancer patients J Clin Oncol 19 1207–25 Occurrence Handle11181687 Occurrence Handle1:CAS:528:DC%2BD3MXhvFertrc%3D
HF Dvorak LF Brown M Detmar AM Dvorak (1995) ArticleTitleVascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis Am J Pathol 146 1029–39 Occurrence Handle7538264 Occurrence Handle1:CAS:528:DyaK2MXmt1Kkt7g%3D
Q Jin K Hemminki K Enquist P Lenner E Grzybowska R Klaes et al. (2005) ArticleTitleVascular endothelial growth factor polymorphisms in relation to breast cancer development and prognosis Clin Cancer Res 11 3647–53 Occurrence Handle15897560 Occurrence Handle10.1158/1078-0432.CCR-04-1803 Occurrence Handle1:CAS:528:DC%2BD2MXktFyrsbs%3D
M Yamamori T Sakaeda T Nakamura N Okamura T Tamura N Aoyama et al. (2004) ArticleTitleAssociation of VEGF genotype with mRNA level in colorectal adenocarcinomas Biochem Biophys Res Commun 325 144–50 Occurrence Handle15522212 Occurrence Handle10.1016/j.bbrc.2004.10.005 Occurrence Handle1:CAS:528:DC%2BD2cXpt1artLk%3D
YS Chung K Maeda M Sowa (1996) ArticleTitlePrognostic value of angiogenesis in gastrointestinal tumors Eur J Cancer 32A 2501–5 Occurrence Handle9059339 Occurrence Handle10.1016/S0959-8049(96)00382-6 Occurrence Handle1:STN:280:DyaK2s3ht1CrsQ%3D%3D
K Maeda YS Chung Y Ogawa S Takatsuka SM Kang M Ogawa et al. (1996) ArticleTitlePrognostic value of vascular endothelial growth factor expression in gastric carcinoma Cancer 77 858–63 Occurrence Handle8608475 Occurrence Handle10.1002/(SICI)1097-0142(19960301)77:5<858::AID-CNCR8>3.0.CO;2-A Occurrence Handle1:STN:280:DyaK287osFelsA%3D%3D
G Neufeld T Cohen S Gengrinovitch Z Poltorak (1999) ArticleTitleVascular endothelial growth factor (VEGF) and its receptors FASEB J 13 9–22 Occurrence Handle9872925 Occurrence Handle1:CAS:528:DyaK1MXlt1ygsQ%3D%3D
N Ferrara (2002) ArticleTitleVEGF and the quest for tumour angiogenesis factors Nat Rev Cancer 2 795–803 Occurrence Handle12360282 Occurrence Handle10.1038/nrc909 Occurrence Handle1:CAS:528:DC%2BD38XnsVGrtbk%3D
CJ Watson NJ Webb MJ Bottomley PE Brenchley (2000) ArticleTitleIdentification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production Cytokine 12 1232–5 Occurrence Handle10930302 Occurrence Handle10.1006/cyto.2000.0692 Occurrence Handle1:CAS:528:DC%2BD3cXltlOqsbw%3D
W Renner S Kotschan C Hoffmann B Obermayer-Pietsch E Pilger (2000) ArticleTitleA common 936 C/T mutation in the gene for vascular endothelial growth factor is associated with vascular endothelial growth factor plasma levels J Vasc Res 37 443–8 Occurrence Handle11146397 Occurrence Handle10.1159/000054076 Occurrence Handle1:CAS:528:DC%2BD3MXoslGmsQ%3D%3D
RS Saad KM Jasnosz JF Silverman (2003) ArticleTitleEndoglin (CD105) expression in endometrial carcinoma Int J Gynecol Pathol 22 248–53 Occurrence Handle12819391 Occurrence Handle10.1097/01.PGP.0000070852.25718.37
CA Brewer JJ Setterdahl MJ Li JM Johnston JL Mann ME McAsey (2000) ArticleTitleEndoglin expression as a measure of microvessels density in cervical cancer Obstet Gynecol 96 224–8 Occurrence Handle10908767 Occurrence Handle10.1016/S0029-7844(00)00864-4 Occurrence Handle1:CAS:528:DC%2BD3cXltVOmsr8%3D
RS Saad YL Liu G Nathan J Celebrezze D Medich JF Silverman (2004) ArticleTitleEndoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer Mod Pathol 17 197–203 Occurrence Handle14657950 Occurrence Handle10.1038/modpathol.3800034 Occurrence Handle1:CAS:528:DC%2BD2cXmsVOisrg%3D
B Bodey B Bode SuffixJr SE Siegel HE Kaiser (1998) ArticleTitleOver-expression of endoglin (CD105): a marker of breast carcinoma-induced neovascularization Anticancer Res 18 3621–8 Occurrence Handle9858949 Occurrence Handle1:CAS:528:DyaK1MXntFKr
MI Koukourakis D Papazoglou A Giatromanolaki G Bougioukas E Maltezos E Sivridis (2004) ArticleTitleVEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer Lung Cancer 46 293–8 Occurrence Handle15541813 Occurrence Handle10.1016/j.lungcan.2004.04.037
Tzanakis N, Gazouli M, Rallis G, Giannopoulos G, Papaconstantinou J, Theodoropoulos G, et al. vascular endothelial growth factor polymorphisms in gastric cancer development, prognosis and survival. J Surg Oncol 2006 (in press)
A Couvelard F Paraf V Gratio JY Scoazec D Henin C Degott et al. (2000) ArticleTitleAngiogenesis in the neoplastic sequence of Barrett's esophagus: correlation with VEGF expression J Pathol 192 14–8 Occurrence Handle10951394 Occurrence Handle10.1002/1096-9896(2000)9999:9999<::AID-PATH709>3.0.CO;2-F Occurrence Handle1:CAS:528:DC%2BD3cXmvVWgt70%3D
Y Kitadai K Haruma T Tokutomi S Tanaka K Sumii M Carvalho et al. (1998) ArticleTitleSignificance of vessel count and vascular endothelial growth factor in human esophageal carcinoma Clin Cancer Res 4 2195–200 Occurrence Handle9748139 Occurrence Handle1:CAS:528:DyaK1cXmslCjsLw%3D
JR Du Y Jiang YM Zhang H Fu (2003) ArticleTitleVascular endothelial growth factor and microvascular density in esophageal and gastric carcinoma World J Gastroenterol 9 1604–6 Occurrence Handle12854174 Occurrence Handle1:CAS:528:DC%2BD3sXoslajurw%3D
N Weidner JP Semple WR Welch J Folkman (1991) ArticleTitleTumor angiogenesis and metastasis: correlation in invasive breast carcinoma New Engl J Med 324 1–8 Occurrence Handle1701519 Occurrence Handle1:STN:280:DyaK3M%2FnsVWquw%3D%3D Occurrence Handle10.1056/NEJM199101033240101
C Fondevila JP Metges J Fuster JJ Grau A Palacin A Castells et al. (2004) ArticleTitlep53 and VEGF expression are independent predictors of tumor recurrence and survival following curative resection of gastric cancer Br J Cancer 90 206–15 Occurrence Handle14710231 Occurrence Handle10.1038/sj.bjc.6601455 Occurrence Handle1:CAS:528:DC%2BD2cXhtFKgtQ%3D%3D
A Kleespies M Guba KW Jauch JC Bruns (2004) ArticleTitleVascular endothelial growth factor in esophageal cancer J Surg Oncol 87 95–104 Occurrence Handle15282704 Occurrence Handle10.1002/jso.20070 Occurrence Handle1:CAS:528:DC%2BD2cXns1Ghtrk%3D
E Fonsatti M Maio (2004) ArticleTitleHighlights on endoglin (CD105): from basic findings towards clinical applications in human cancer J Transl Med 2 18 Occurrence Handle15193152 Occurrence Handle10.1186/1479-5876-2-18
JP Dales S Garcia S Carpentier L Andrac O Ramuz MN Lavaut et al. (2004) ArticleTitlePrediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n = 905) Br J Cancer 90 1216–21 Occurrence Handle15026804 Occurrence Handle10.1038/sj.bjc.6601452 Occurrence Handle1:CAS:528:DC%2BD2cXitV2rsrs%3D
C Li R Gardy BK Seon SE Duff S Abdalla A Renehan et al. (2003) ArticleTitleBoth high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis Br J Cancer 88 1424–31 Occurrence Handle12778073 Occurrence Handle10.1038/sj.bjc.6600874 Occurrence Handle1:CAS:528:DC%2BD3sXktFOgurk%3D
HB Salvesen MG Gulluoglu I Stefansson LA Akslen (2003) ArticleTitleSignificance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas APMIS 111 1011–8 Occurrence Handle14629267 Occurrence Handle10.1111/j.1600-0463.2003.apm1111103.x
JX Yu XT Zhang YQ Liao QY Zhang H Chen M Lin et al. (2003) ArticleTitleRelationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance World J Gastroenterol 9 2866–9 Occurrence Handle14669355 Occurrence Handle1:CAS:528:DC%2BD2cXmt1Crsg%3D%3D
K Maeda SM Kang N Onoda M Ogawa Y Kato T Sawada et al. (1999) ArticleTitleVascular endothelial growth factor expression in preoperative biopsy specimens correlate with disease recurrence in patients with early gastric carcinoma Cancer 86 566–71 Occurrence Handle10440683 Occurrence Handle10.1002/(SICI)1097-0142(19990815)86:4<566::AID-CNCR4>3.0.CO;2-1 Occurrence Handle1:STN:280:DyaK1MzmvFOntA%3D%3D
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nikiteas, N., Tzanakis, N., Theodoropoulos, G. et al. Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. Gastric Cancer 10, 12–17 (2007). https://doi.org/10.1007/s10120-006-0401-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10120-006-0401-8