This semiquantitative immunohistochemical study investigated the clinical significance of S100A4 and vascular endothelial growth factor C (VEGF-C) protein expression in gastric carcinoma. Correlations between S100A4 and VEGF-C immunoreactivity and clinicopathological characteristics were evaluated using 108 gastric carcinoma specimens and 20 specimens of tissue adjacent to gastric carcinoma. S100A4 and VEGF-C expression in carcinoma was higher than that in adjacent tissues. S100A4 expression was significantly related to tumour size and lymph node metastasis, whereas VEGF-C expression was associated with invasion depth, lymph node metastasis and tumour, node, metastasis (TNM) stage. A significant correlation was found between S100A4 and VEGF-C expression. Patients expressing S100A4 or VEGF-C showed no significant reduction in 5-year survival rate compared with those not expressing these proteins. Sex, age, tumour size, invasion depth, lymph node involvement, TNM stage, S100A4 expression and VEGF-C expression had a common effect on carcinoma prognosis but none was an independent prognostic factor.
JemalASiegelRWardE: Cancer statistics, 2008. CA Cancer J Clin2008; 58: 71–96.
3.
JemalASiegelRWardE: Cancer statistics, 2009. CA Cancer J Clin2009; 59: 225–249.
4.
JemalASiegelRXuJ: Cancer statistics, 2010. CA Cancer J Clin2010; 60: 277–304.
5.
DurraniAAYaqoobNAbbasiS: Pattern of upper gastrointestinal malignancies in Northern Punjab. Pak J Med Sci2009; 25: 302–307.
6.
ChenXMChenGYWangZR: Detection of micrometastasis of gastric carcinoma in peripheral blood circulation. World J Gastroenterol2004; 10: 804–808.
7.
WenhuaZFanghaiH: Surgical therapy of gastric cancer in China. J Pract Oncol2008; 23: 91–93.
8.
KimDYJooJKRyuSY: Factors related to lymph node metastasis and surgical strategy used to treat early gastric carcinoma. World J Gastroenterol2004; 10: 737–740.
9.
KunisakiCShimadaHTakahashiM: Prognostic factors in early gastric cancer. Hepatogastroenterology2001; 48: 294–298.
10.
ZhangMZhuGYZhangHF: Clinicopathologic characteristics and prognosis of mucinous gastric carcinoma. J Surg Oncol2010; 102: 64–67.
11.
DeguchiKIchikawaDSogaK: Clinical significance of vascular endothelial growth factors C and D and chemokine receptor CCR7 in gastric cancer. Anticancer Res2010; 30: 2361–2366.
12.
ArigamiTNatsugoeSUenosonoY: Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pN0 early gastric cancer. J Surg Oncol2009; 99: 148–153.
13.
WangYYYeZYZhaoZS: High-level expression of S100A4 correlates with lymph node metastasis and poor prognosis in patients with gastric cancer. Ann Surg Oncol2010; 17: 89–97.
14.
ChoYGNamSWKimTY: Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer. APMIS2003; 111: 539–545.
15.
TanakaTIshiguroHKuwabaraY: Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. J Exp Clin Cancer Res2010; 29: 83.
16.
ZhangCHaoLWangL: Elevated IGFIR expression regulating VEGF and VEGF-C predicts lymph node metastasis in human colorectal cancer. BMC Cancer2010; 10: 184.
17.
SunJGWangYChenZT: Detection of lymphangiogenesis in non-small cell lung cancer and its prognostic value. J Exp Clin Cancer Res2009; 28: 21.
18.
TianXCongMZhouW: Relationship between protein expression of VEGF-C, MMP-2 and lymph node metastasis in papillary thyroid cancer. J Int Med Res2008; 36: 699–703.
19.
AiKXLuLYHuangXY: Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer. World J Gastroenterol2008; 14: 1931–1935.
20.
SteinUArltFWaltherW: The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology2006; 131: 1486–1500.
21.
KwakJMLeeHJKimSH: Expression of protein S100A4 is a predictor of recurrence in colorectal cancer. World J Gastroenterol2010; 16: 3897–3904.
22.
KikuchiNHoriuchiAOsadaR: Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: an important autocrine/paracrine factor in tumor progression. Cancer Sci2006; 97: 1061–1069.
23.
YaoRLopez-BeltranAMaclennanGT: Expression of S100 protein family members in the pathogenesis of bladder tumors. Anticancer Res2007; 27: 3051–3058.
24.
JiJZhaoLWangX: Differential expression of S100 gene family in human esophageal squamous cell carcinoma. J Cancer Res Clin Oncol2004; 130: 480–486.
25.
KimYJKimMAImSA: Metastasis-associated protein S100A4 and p53 predict relapse in curatively resected stage III and IV (M0) gastric cancer. Cancer Invest2008; 26: 152–158.
26.
LeeWJHongRLLaiIR: Reappraisal of the new UICC staging system for gastric cancer: problem in lymph node stage. Hepatogastroenterology2002; 49: 860–864.
27.
BoyeKMaelandsmoGM: S100A4 and metastasis: A small actor playing many roles. Am J Pathol2010; 176: 528–535.
28.
MatsumotoKIrieASatohT: Expression of S100A2 and S100A4 predicts for disease progression and patient survival in bladder cancer. Urology2007; 70: 602–607.
29.
YoonCSHyungWJLeeJH: Expression of S100A4, E-cadherin, alpha- and beta-catenin in gastric adenocarcinoma. Hepatogastroenterology2008; 55: 1916–1920.
30.
SlaeemMKweonMHJohnsonJJ: S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Proc Natl Acad Sci U S A2006; 103: 14825–14830.
31.
SemovAMorenoMJOnichtchenkoA: Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation. J Biol Chem2005; 280: 20833–20841.
32.
Moriyama-KitaMEndoYYonemuraY: S100A4 regulates E-cadherin expression in oral squamous cell carcinoma. Cancer Lett2005; 230: 211–218.
33.
AlitaloKCarmelietP: Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell2002; 1: 219–227.
34.
KodamaMKitadaiYTanakaM: Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms. Clin Cancer Res2008; 14: 7205–7214.
35.
DengJLiangHSunD: Vascular endothelial growth factor-D is correlated with hepatic metastasis from gastric cancer after radical gastrectomy. Surgery2009; 146: 896–905.
36.
WangTBDengMHQiuWS: Association of serum vascular endothelial growth factor-C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer. World J Gastroenterol2007; 13: 1794–1798.
