Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 6/2010

01-06-2010 | Hepatobiliary Tumors

Prognostic Significance of c-erbB-2 and Vascular Endothelial Growth Factor in Colorectal Liver Metastases

Authors: Jinggui Chen, MD, Qingguo Li, MD, Changjian Wang, MD, Jianghong Wu, MD, PhD, Guangfa Zhao, MD, PhD

Published in: Annals of Surgical Oncology | Issue 6/2010

Login to get access

Abstract

Background

The prognostic value of c-erbB-2 and vascular endothelial growth factor (VEGF) expression in colorectal liver metastases (CLM) is unclear. The purpose of this study was to clarify the relationship of c-erbB-2 and VEGF with the clinicopathological parameters and the survival results in CLM.

Methods

For 44 patients who had undergone liver resection for CLM at Fudan University Cancer Hospital from 2000 to 2007, the expression of c-erbB-2 and VEGF in CLM and the corresponding primary cancer specimens were evaluated immunohistochemically. The correlations among c-erbB-2 and VEGF, clinicopathologic factors, and survival were then statistically analyzed.

Results

Positive expression rates of c-erbB-2 and VEGF in CLM lesions were 38.64% and 52.72%, respectively. The expression of c-erbB-2 and VEGF in CLM were similar to that of corresponding primary tumor. c-erbB-2 expression correlated with number of metastatic lesions and the distribution of liver metastases. The expression of VEGF correlated with the size of liver metastatic lesion and distribution of liver metastases. A statistically significant association between the expression of c-erbB-2 and VEGF in both CLM and primary tumor was noted. Univariate analysis showed that VEGF was a prognostic factor. However, on multivariate analysis, expression of VEGF was not an independent prognostic marker. Patients with both negative expression of c-erbB-2 and VEGF expression had a better outcome than others.

Conclusions

VEGF might be a statistically significant prognostic factor. The combined analysis of c-erbB-2 and VEGF is of added prognostic value. An association exists between c-erbB-2 and VEGF. However, further studies are required to confirm this issue.
Literature
1.
2.
Sarpel U, Bonavia AS, Grucela A, et al. Does anatomic versus nonanatomic resection affect recurrence and survival in patients undergoing surgery for colorectal liver metastasis? Ann Surg Oncol. 2009;16:379–84.CrossRefPubMed
3.
Simmonds PC, Primrose JN, Colquitt JL, et al. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer. 2006;94:982–99.CrossRefPubMed
4.
Pawlik TM, Choti MA. Surgical therapy for colorectal metastases to the liver. J Gastrointest Surg. 2007;11:1057–77.CrossRefPubMed
5.
Yang JL, Ow KT, Russell PJ, et al. Higher expression of oncoproteins c-myc, c-erbB-2/neu, PCNA, and p53 in metastasizing colorectal cancer than in nonmetastasizing tumors. Ann Surg Oncol. 1996;3:574–9.CrossRefPubMed
6.
Press MF, Hung G, Godolphin W, et al. Sensitivity of HER-2/neu antibodies in archival tissue samples—potential source of error in immunohistochemical studies of oncogene expression. Cancer Res. 1994;54:2771–7.PubMed
7.
Seliger B, Rongcun Y, Atkins D, et al. HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels independently of tumor grading and staging and can be recognized by HLA-A2.1-restricted cytotoxic T lymphocytes. Int J Cancer. 2000;87:349–59.CrossRefPubMed
8.
de Graeff P, Crijns APG, ten Hoor KA, et al. The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer. Br J Cancer. 2008;99:341–9.CrossRefPubMed
9.
Cascinu S, Staccioli MP, Gasparini G, et al. Expression of vascular endothelial growth factor can predict event-free survival in stage II colon cancer. Clin Cancer Res. 2000;6:2803–7.PubMed
10.
Bradbury PA, Zhai RH, Ma C, et al. Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis. Clin Cancer Res. 2009;15:4680–5.CrossRefPubMed
11.
Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26:4672–8.CrossRefPubMed
12.
Ellis LM, Hicklin DJ. Pathways mediating resistance to vascular endothelial growth factor-targeted therapy. Clin Cancer Res. 2008;14:6371–5.CrossRefPubMed
13.
Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER-2/neu proto-oncogene in human-breast and ovarian-cancer. Science. 1989;244:707–12.CrossRefPubMed
14.
Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20:719–26.CrossRefPubMed
15.
McKay JA, Loane JF, Ross VG, et al. c-erbB-2 is not a major factor in the development of colorectal cancer. Br J Cancer. 2002;86:568–73.CrossRefPubMed
16.
Park DI, Kang MS, Oh SJ, et al. HER-2/neu overexpression is an independent prognostic factor in colorectal cancer. Int J Colorectal Dis. 2007;22:491–7.CrossRefPubMed
17.
Baiocchi G, Lopes A, Coudry RA, et al. ErbB family immunohistochemical expression in colorectal cancer patients with higher risk of recurrence after radical surgery. Int J Colorectal Dis. 2009;24:1059–68.CrossRefPubMed
18.
Osako T, Miyahara M, Uchino S, et al. Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the correlation with patient survival. Oncology. 1998;55:548–55.CrossRefPubMed
19.
Schuell B, Gruenberger T, Scheithauer W, et al. HER 2/neu protein expression in colorectal cancer. BMC Cancer. 2006;6:123.
20.
21.
Claffey KP, Robinson GS. Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis. Cancer Metastasis Rev. 1996;15:165–76.CrossRefPubMed
22.
Maehara Y, Kabashima A, Koga T, et al. Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma. Surgery. 2000;128:408–16.CrossRefPubMed
23.
Kim JG, Chae YS, Sohn SK, et al. Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with colorectal cancer. Clin Cancer Res. 2008;14:62–6.CrossRefPubMed
24.
Seo Y, Baba H, Fukuda T, et al. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer. 2000;88:2239–45.CrossRefPubMed
25.
Takeda A, Stoeltzing O, Ahmad SA, et al. Role of angiogenesis in the development and growth of liver metastasis. Ann Surg Oncol. 2002;9:610–6.CrossRefPubMed
26.
Kondo Y, Arii S, Mori A, et al. Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line. Clin Cancer Res. 2000;6:622–30.PubMed
27.
Andre T, Kotelevets L, Vaillant JC, et al. VEGF, VEGF-B, VEGF-C, and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa. Int J Cancer. 2000;86:174–81.CrossRefPubMed
28.
Randal J. Antiangiogenesis drugs target specific cancers, mechanisms. J Natl Cancer Inst. 2000;92:520–2.CrossRefPubMed
29.
Eatock MM, Schatzlein A, Kaye SB. Tumour vasculature as a target for anticancer therapy. Cancer Treat Rev. 2000;26:191–204.CrossRefPubMed
30.
Kuramochi H, Hayashi K, Uchida K, et al. Vascular endothelial growth factor messenger RNA expression level is preserved in liver metastases compered with corresponding primary colorectal cancer. Clin Cancer Res. 2006;12:29–33.CrossRefPubMed
31.
Mooteri S, Rubin D, Leurgans S, et al. Tumor angiogenesis in primary and metastatic colorectal cancers. Dis Colon Rectum. 1996;39:1073–80.CrossRefPubMed
32.
Berney CR, Yang JL, Fisher RJ, et al. Vascular endothelial growth factor expression is reduced in liver metastasis from colorectal cancer and correlates with urokinase-type plasminogen activator. Anticancer Res. 1998;18:973–7.PubMed
33.
Lee JC, Chow NH, Wang ST, et al. Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer. 2000;36:748–53.CrossRefPubMed
34.
Tokunaga T, Oshika Y, Abe Y, et al. Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer. Br J Cancer. 1998;77:998–1002.PubMed
35.
Wolmark N, Fisher B, Wieand HS, et al. The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer: results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg. 1984;199:375–82.CrossRefPubMed
36.
Hohenberger P, Schlag PM, Gerneth T, et al. Pre- and postoperative carcinoembryonic antigen determinations in hepatic resection for colorectal metastases: predictive value and implications for adjuvant treatment based on multivariate analysis. Ann Surg. 1994;219:135–43.CrossRefPubMed
37.
Mann CD, Metcalfe MS, Leopardi LN, et al. The clinical risk score: emerging as a reliable preoperative prognostic index in hepatectomy for colorectal metastases. Arch Surg. 2004;139:1168–72.CrossRefPubMed
38.
Yen L, You XL, Al Moustafa AE, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene. 2000;19:3460–9.CrossRefPubMed
39.
Yen L, Benlimame N, Nie ZR, et al. Differential regulation of tumor angiogenesis by distinct ErbB homo- and heterodimers. Mol Biol Cell. 2002;13:4029–44.CrossRefPubMed
40.
Yang WT, Klos K, Yang Y, et al. ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer. 2002;94:2855–61.CrossRefPubMed
41.
Klos KS, Wyszomierski SL, Sun MH, et al. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6 K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006;66:2028–37.CrossRefPubMed
42.
Petit AMV, Rak J, Hung MC, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo—angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997;151:1523–30.PubMed
Metadata
Title
Prognostic Significance of c-erbB-2 and Vascular Endothelial Growth Factor in Colorectal Liver Metastases
Authors
Jinggui Chen, MD
Qingguo Li, MD
Changjian Wang, MD
Jianghong Wu, MD, PhD
Guangfa Zhao, MD, PhD
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 6/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0897-3

Other articles of this Issue 6/2010

Annals of Surgical Oncology 6/2010 Go to the issue

Breast Oncology

Changes in Circulating Tumor Cell Detection in Patients with Localized Breast Cancer Before and After Surgery

Medical Oncology

Increased Use of Percutaneous Technique for Totally Implantable Venous Access Devices. Is It Real Progress? A 27-Year Comprehensive Review on Early Complications

Gastrointestinal Oncology

In Reply: Does Metastatic Lymph Node Ratio Really Suit for Prognostic Prediction of the D1 Lymphadenectomy?

Breast Oncology

Liver Resection for Multimodal Treatment of Breast Cancer Metastases: Identification of Prognostic Factors

Gastrointestinal Oncology

Extended Esophagectomy in Elderly Patients with Esophageal Cancer: Minor Effect of Age Alone in Determining the Postoperative Course and Survival

Gastrointestinal Oncology

In Reply: Five Reasons Why Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy Must Be Regarded as the New Standard of Care for Diffuse Malignant Peritoneal Mesothelioma