SOX group F genes are important regulators of angiogenesis and lymphangiogenesis. The aim of the present study was to examine the relationships between Sox group F expression and clinicopathological factors in gastric cancer. Three hundred and fifteen gastric cancer tissues and the corresponding normal gastric tissue were obtained from the tumor bank at the National Cancer Center, Korea. SOX group F mRNA levels in these tissues were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). The serum levels of SOX 18 proteins in 219 gastric cancer patients and in 30 healthy volunteers were also measured by enzyme-linked immunosorbent assay. Furthermore, immunohistochemistry (IHC) was performed on 679 gastric cancer tissues and the clinicopathological characteristics, as well as the survival rates of SOX 18 positive and negative gastric cancers were compared. RT-PCR showed that SOX group F mRNA was increased in the gastric cancer tissues compared to the normal gastric tissues (p < 0.001, respectively). The serum levels of SOX 18 protein were also increased in gastric cancer patients compared to healthy volunteers. IHC showed that of the 679 gastric cancer cases, 177 (26.1%) were positive for SOX 18 expression in their tumor stroma, and the frequencies of both lymphovascular invasion and lymph node metastases were higher in the SOX 18 positive than in the negative group. Both the 5-year survival and the recurrence-free survival were shorter for SOX 18 positive tumors (p 5 0.023 and 0.012, respectively). SOX 18 expression might be a prognostic tumor marker and a potential therapeutic target in gastric cancer.Gastric cancer is the fourth most common cancer in the world and, annually, about 1 million new cases are diagnosed worldwide. 1 In South Korea, gastric cancer has a higher incidence than any other cancer, and is the third most common cause of death from cancer. 2 The prognosis of patients with gastric cancer is influenced by the presence of lymph node (LN) metastasis, therefore, an accurate and reliable indicator is required to predict the presence of LN metastasis. Furthermore, a biomolecular predictor of LN metastasis can be a prognostic marker or a potential therapeutic target. [3][4][5] Recently, angiogenesis and lymphangiogenesis were found to be critically required for solid tumor growth, invasion and distant metastases. 6-8 Previous molecular and cellular analyses have identified a number of factors of angiogenesis and lymphangiogenesis, such as, the fibroblast growth factor, the vascular endothelial growth factor and angiopoietin. 9-13 Similarly, specific gene-based studies recently discovered the lymphangiogenesis associated SOX genes (i.e., sex determining region Y box genes). 14,15 The SOX genes constitute a large family of diverse and well-conserved genes, which encode transcription factors. [16][17][18] Members of this gene family are subdivided on a homology basis into ten groups (A to J), and SOX group F comprises the SOX 7, 17 and 18 genes. 17 SOX 18 is transiently expressed in the ...