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

06.11.2017 | Original Research

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

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

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 1/2019

Einloggen, um Zugang zu erhalten

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.
Literatur
3.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRefPubMed Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRefPubMed
18.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Role of VEGF, CD105, and CD31 in the Prognosis of Colorectal Cancer Cases
verfasst von
Salem Y. Mohamed
Hanan Lotfy Mohammed
Hanaa M. Ibrahim
Elshaimaa M. Mohamed
Mona Salah
Publikationsdatum
06.11.2017
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 1/2019
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-017-0014-y

Weitere Artikel der Ausgabe 1/2019

Journal of Gastrointestinal Cancer 1/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.