Skip to main content
Top
Published in: Journal of Gastrointestinal Cancer 1/2019

01-03-2019 | Original Research

Role of VEGF, CD105, and CD31 in the Prognosis of Colorectal Cancer Cases

Authors: Salem Y. Mohamed, Hanan Lotfy Mohammed, Hanaa M. Ibrahim, Elshaimaa M. Mohamed, Mona Salah

Published in: Journal of Gastrointestinal Cancer | Issue 1/2019

Login to get access

Abstract

Introduction

Colorectal cancer (CRC) incidence is increasing globally. It is ranked as the second most common cancer in women and the third most in men. Angiogenesis plays a significant role in the development and spread of colorectal cancer. Angiogenesis has been proposed as a prognostic marker in a variety of human neoplasms. In this regard, markers of angiogenic endothelial cells are emerging as targets for cancer therapy.

Aim of the Work

The aim of this study is to evaluate the prognostic impact of tumor angiogenesis assessed by microvessel density (MVD) counting using CD31 and CD105 along with VEGF immunostaining in colorectal cancer patients.

Methods

VEGF, CD31, and CD105 expressions were evaluated using immunohistochemical staining in 50 patients with colorectal cancer. The relationship between their expressions and clinicopathological factors and outcome of patients were analyzed.

Results

The VEGF expression (70% of the cases) correlated significantly with larger tumor size, higher grade, and advanced tumor stage (p = 0.006, p < 0.001, p < 0.001), respectively. The mean MVD was 24.2 ± VMD by CD105 (p = 0.10.65 019 for CD105, 19.2 ± 8.41 for CD31, respectively. MVD by CD31 (p = 0.023)) and was significant predictive factors for overall survival. Furthermore, the VEGF expression (p = < 0.001) was a significant predictive factor for DFS. There was a statistically significant association between the recurrence rates with both VEGF and CD105 (p < 0.001) but not significant with CD31.

Conclusion

CRC patients with high VEGF, CD105, and CD31 expression showed poor prognosis. The immunohistochemical markers could be used for stratification of patients into low-risk and high-risk groups.
Literature
3.
go back to reference Bendardaf R, Buhmeida A, Hilska M, et al. VEGF-1expression in colorectal cancer is associated with disease localization, stage, and long-term disease-specific survival. Anticancer Res. 2008;28(6B):3865–70.PubMed Bendardaf R, Buhmeida A, Hilska M, et al. VEGF-1expression in colorectal cancer is associated with disease localization, stage, and long-term disease-specific survival. Anticancer Res. 2008;28(6B):3865–70.PubMed
4.
go back to reference Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–410. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–410.
5.
go back to reference Cammarota R, Bertolini V, Penne G. The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker. J Transl Med. 2010;8:112.CrossRefPubMedPubMedCentral Cammarota R, Bertolini V, Penne G. The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker. J Transl Med. 2010;8:112.CrossRefPubMedPubMedCentral
6.
go back to reference Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69:34–10.CrossRef Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69:34–10.CrossRef
7.
go back to reference Chen YB, Wan DS, Zhan YQ, Zhou ZW, Li W, Chen G. Correlation of tumor microvessel density to metastasis and recurrence of rectal cancer. Ai Zheng. 2004;23:1203–6.PubMed Chen YB, Wan DS, Zhan YQ, Zhou ZW, Li W, Chen G. Correlation of tumor microvessel density to metastasis and recurrence of rectal cancer. Ai Zheng. 2004;23:1203–6.PubMed
8.
go back to reference Chung J, Braunschweig T, Hong S, et al. Assessment of vascular endothelial growth factor in formalin fixed, paraffin-embedded colon cancer specimens using a well-based reverse phase protein array. Proteome Sci. 2014;12:27.CrossRefPubMedPubMedCentral Chung J, Braunschweig T, Hong S, et al. Assessment of vascular endothelial growth factor in formalin fixed, paraffin-embedded colon cancer specimens using a well-based reverse phase protein array. Proteome Sci. 2014;12:27.CrossRefPubMedPubMedCentral
10.
go back to reference Dassoulas K, Gazouli M, Theodoropoulos M, et al. Vascular endothelial growth factor and endoglin expression in colorectal cancer. J Cancer Res Clin Oncol. 2010;136(5):703–8.CrossRefPubMed Dassoulas K, Gazouli M, Theodoropoulos M, et al. Vascular endothelial growth factor and endoglin expression in colorectal cancer. J Cancer Res Clin Oncol. 2010;136(5):703–8.CrossRefPubMed
11.
go back to reference Deliu C, Ciurea P, Neagoe D, et al. Evaluation of Angiogenesis in Colorectal Cancer. Current Health Sciences. 2015;41(2). Deliu C, Ciurea P, Neagoe D, et al. Evaluation of Angiogenesis in Colorectal Cancer. Current Health Sciences. 2015;41(2).
12.
go back to reference Deliu IC, Neagoe CD, Beznă M, et al. Correlations between endothelial cell markers CD31, CD34 and CD105 in colorectal carcinoma. Rom J Morphol Embryol. 2016;57(3):1025–30.PubMed Deliu IC, Neagoe CD, Beznă M, et al. Correlations between endothelial cell markers CD31, CD34 and CD105 in colorectal carcinoma. Rom J Morphol Embryol. 2016;57(3):1025–30.PubMed
13.
go back to reference Ferroni P, Palmirotta R, Spila A, Martini F, et al. Prognostic value of carcinoembryonic antigen and vascular endothelial growth factor tumor tissue content in colorectal cancer. Oncology. 2006;71:176–84.CrossRefPubMed Ferroni P, Palmirotta R, Spila A, Martini F, et al. Prognostic value of carcinoembryonic antigen and vascular endothelial growth factor tumor tissue content in colorectal cancer. Oncology. 2006;71:176–84.CrossRefPubMed
14.
go back to reference Gulubova M, Vlaykova T. Prognostic significance of mast cell number and microvascular density for the survival of patients with primary colorectal cancer. J Gastroenterol Hepatol. 2009;4(7):1265–75.CrossRef Gulubova M, Vlaykova T. Prognostic significance of mast cell number and microvascular density for the survival of patients with primary colorectal cancer. J Gastroenterol Hepatol. 2009;4(7):1265–75.CrossRef
15.
go back to reference Hamilton SR, Vogelstein B, Kudo S, Riboli E, Nakamura S, et al. World Health Organization Classification Of Tumours: Pathology and genetics of tumors of the digestive system. Lyon: IARC Press; 2000. p. 104–143. Hamilton SR, Vogelstein B, Kudo S, Riboli E, Nakamura S, et al. World Health Organization Classification Of Tumours: Pathology and genetics of tumors of the digestive system. Lyon: IARC Press; 2000. p. 104–143.
16.
18.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed
19.
go back to reference Jamshidi S, Zargaran M, Baghaei F, et al. An immunohistochemical survey to evaluate the expression of CD105 and CD34 in ameloblastoma and odontogenic keratocyst. J Dent (Shiraz). 2014;15(4):192–8. Jamshidi S, Zargaran M, Baghaei F, et al. An immunohistochemical survey to evaluate the expression of CD105 and CD34 in ameloblastoma and odontogenic keratocyst. J Dent (Shiraz). 2014;15(4):192–8.
20.
go back to reference Jung I, Gurzu S, Ranica M, et al. The differences between the endothelial area marked with CD31 and CD105 in colorectal carcinomas by computer-assisted morphometrical analysis. Romanian J Morphol Embryol. 2009;50(2):239–43. Jung I, Gurzu S, Ranica M, et al. The differences between the endothelial area marked with CD31 and CD105 in colorectal carcinomas by computer-assisted morphometrical analysis. Romanian J Morphol Embryol. 2009;50(2):239–43.
22.
go back to reference Khorana AA, Ryan CK, Cox C, Eberly S, et al. Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with Stage II and Stage III colon carcinoma: a role for the host response in prognosis. Cancer. 2003;97:960–8.CrossRefPubMed Khorana AA, Ryan CK, Cox C, Eberly S, et al. Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with Stage II and Stage III colon carcinoma: a role for the host response in prognosis. Cancer. 2003;97:960–8.CrossRefPubMed
23.
go back to reference Li C, Gardy R, Seon BK, et al. Both high intratumoral microvessel densities determined using a CD105 antibody, and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer. 2003;88:1424–31.CrossRefPubMedPubMedCentral Li C, Gardy R, Seon BK, et al. Both high intratumoral microvessel densities determined using a CD105 antibody, and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer. 2003;88:1424–31.CrossRefPubMedPubMedCentral
24.
go back to reference Minhajat R, Mori D, Yamasaki F, et al. Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers. Virchows Arch. 2006;448(2):127–34. Epub 2005 Sep 22CrossRefPubMed Minhajat R, Mori D, Yamasaki F, et al. Endoglin (CD105) expression in angiogenesis of colon cancer: analysis using tissue microarrays and comparison with other endothelial markers. Virchows Arch. 2006;448(2):127–34. Epub 2005 Sep 22CrossRefPubMed
25.
go back to reference Mohamed AH, Abd El All SH, Kamel AA, et al. Correlation of Vascular Endothelial Growth Factor Expression and Neovascularization with Colorectal Carcinoma: A Pilot Study .journal of adenocarcinoma. 2016;1(1):5 Mohamed AH, Abd El All SH, Kamel AA, et al. Correlation of Vascular Endothelial Growth Factor Expression and Neovascularization with Colorectal Carcinoma: A Pilot Study .journal of adenocarcinoma. 2016;1(1):5
26.
go back to reference Mokhtar N, Gouda I, Adel I. Cancer pathology registry (2003–2004) and time trend analysis. In: Mokhtar N, Gouda I, Adel I, editors. Malignant digestive system tumors. Cairo: NCI, Elshere press; 2007. p. 55–67. Mokhtar N, Gouda I, Adel I. Cancer pathology registry (2003–2004) and time trend analysis. In: Mokhtar N, Gouda I, Adel I, editors. Malignant digestive system tumors. Cairo: NCI, Elshere press; 2007. p. 55–67.
27.
go back to reference Nakayama H, Enzan H, Miyazaki E, et al. Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumourstroma. J Clin Pathol. 2000;53(8):626–9. Nakayama H, Enzan H, Miyazaki E, et al. Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumourstroma. J Clin Pathol. 2000;53(8):626–9.
28.
go back to reference Raica M, Cimpean AM, Ribatti D. Angiogenesis in pre-malignant conditions. Eur J Cancer. 2009 Jul;45(11):1924–34.CrossRefPubMed Raica M, Cimpean AM, Ribatti D. Angiogenesis in pre-malignant conditions. Eur J Cancer. 2009 Jul;45(11):1924–34.CrossRefPubMed
29.
go back to reference Redston M. Epithelial neoplasm of the large intestine. In: Odze RD, Goldblum JR, Crawford JM (eds). Surgical pathology of the GI tract, liver, biliary tract, and pancreas. Philadelphia: Saunders; 2004. p. 441–472 Redston M. Epithelial neoplasm of the large intestine. In: Odze RD, Goldblum JR, Crawford JM (eds). Surgical pathology of the GI tract, liver, biliary tract, and pancreas. Philadelphia: Saunders; 2004. p. 441–472
30.
go back to reference Saad RS, Jasnosz KM, Silverman JF. Endoglin (CD105) expression in endometrial carcinoma. Int J Gynecol Pathol. 2003;22:248–53.CrossRefPubMed Saad RS, Jasnosz KM, Silverman JF. Endoglin (CD105) expression in endometrial carcinoma. Int J Gynecol Pathol. 2003;22:248–53.CrossRefPubMed
31.
go back to reference Saad RS, Liu YL, Nathan G, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol. 2004 Feb;17(2):197–203.CrossRefPubMed Saad RS, Liu YL, Nathan G, et al. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol. 2004 Feb;17(2):197–203.CrossRefPubMed
32.
go back to reference Saad RS, El-Gohary YL, Memari E, Liu YL, Silverman JF. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. Hum Pathol. 2005;36:955–61.CrossRefPubMed Saad RS, El-Gohary YL, Memari E, Liu YL, Silverman JF. Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma. Hum Pathol. 2005;36:955–61.CrossRefPubMed
33.
go back to reference Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, et al. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100:1385–92.CrossRefPubMedPubMedCentral Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, et al. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100:1385–92.CrossRefPubMedPubMedCentral
34.
go back to reference Soumaoro LT, Uetake H, Higuchi T, Takagi Y, et al. Cyclooxygenase-2 expression: a significant prognostic indicator for patients with colorectal cancer. Clin Cancer Res. 2004;10:8465–71.CrossRefPubMed Soumaoro LT, Uetake H, Higuchi T, Takagi Y, et al. Cyclooxygenase-2 expression: a significant prognostic indicator for patients with colorectal cancer. Clin Cancer Res. 2004;10:8465–71.CrossRefPubMed
35.
go back to reference Takahashi N, Kawanishi-Tabata R, Haba A, et al. Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res. 2001;7(3):524–32.PubMed Takahashi N, Kawanishi-Tabata R, Haba A, et al. Association of serum endoglin with metastasis in patients with colorectal, breast, and other solid tumors, and suppressive effect of chemotherapy on the serum endoglin. Clin Cancer Res. 2001;7(3):524–32.PubMed
36.
go back to reference Tien YW, Chang KJ, Jeng M, et al. Tumor angiogenesis and its possible role in intravasation of colorectal epithelial cells. Clin Cancer Res. 2001;7(6):1627–32.PubMed Tien YW, Chang KJ, Jeng M, et al. Tumor angiogenesis and its possible role in intravasation of colorectal epithelial cells. Clin Cancer Res. 2001;7(6):1627–32.PubMed
37.
go back to reference Uribarrena AR, Ortego J, Fuentes J, et al. Prognostic value of microvascular density in Dukes A and B (T1–T4, N0, M0) colorectal carcinomas. Gastroenterol Res Pract. 2009;2009:679830.CrossRef Uribarrena AR, Ortego J, Fuentes J, et al. Prognostic value of microvascular density in Dukes A and B (T1–T4, N0, M0) colorectal carcinomas. Gastroenterol Res Pract. 2009;2009:679830.CrossRef
38.
go back to reference Wang Y, Yao X, Ge J, et al. Can vascular endothelial growth factor and microvessel density be used as prognostic biomarkers for colorectal cancer? A systematic review and meta-analysis. Sci World J. 2014:102736. Wang Y, Yao X, Ge J, et al. Can vascular endothelial growth factor and microvessel density be used as prognostic biomarkers for colorectal cancer? A systematic review and meta-analysis. Sci World J. 2014:102736.
39.
go back to reference Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36:169–80.CrossRefPubMed
Metadata
Title
Role of VEGF, CD105, and CD31 in the Prognosis of Colorectal Cancer Cases
Authors
Salem Y. Mohamed
Hanan Lotfy Mohammed
Hanaa M. Ibrahim
Elshaimaa M. Mohamed
Mona Salah
Publication date
01-03-2019
Publisher
Springer US
Published in
Journal of Gastrointestinal Cancer / Issue 1/2019
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-017-0014-y

Other articles of this Issue 1/2019

Journal of Gastrointestinal Cancer 1/2019 Go to the issue