Clinical implications and characteristics of factor forkhead box protein 3 in gastric cancer

Jiang,ChangLi; Wang,WeiHua; Yan,Wei; Zhang,YuHai; Yang,JiangTao; Zhang,Song; Zhang,Cun; Zhang,Wei; Han,Wei; Wang,JunZhi; Zhang,Ying-Qi

doi:10.3892/etm.2011.264

Clinical implications and characteristics of factor forkhead box protein 3 in gastric cancer

Authors:
- ChangLi Jiang
- WeiHua Wang
- Wei Yan
- YuHai Zhang
- JiangTao Yang
- Song Zhang
- Cun Zhang
- Wei Zhang
- Wei Han
- JunZhi Wang
- Ying-Qi Zhang
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Affiliations: Biotechnology Center of the Pharmacy, State Key Laboratory of Cancer Biology, the Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Health Statistics, the Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Pathology, Xi'an Gaoxin Hospital, Xi'an, Shaanxi 710032, P.R. China, Institute of Materia Medica, the Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, National Center for Safety Evaluation of Drugs, National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, P.R. China
Published online on: May 12, 2011 https://doi.org/10.3892/etm.2011.264
Pages: 667-673

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Abstract

Transcription factor forkhead box protein 3 (FOXP3) is a specific marker of naturally occurring regulatory T cells (Tregs). Recently, various reports have suggested that FOXP3 may represent a tumor escape mechanism in cancer cells apart from its roles in Tregs. In the present study, the clinical and biological characteristics of FOXP3 were evaluated in human gastric cancer. The expression and localization of FOXP3 in gastric cancer cell lines was analyzed to evaluate its cellular biological features. Sections of human gastric cancer specimens were stained using immunohistochemistry (IHC) to assess the relationship between FOXP3 expression and tumor differentiation, in order to identify its clinical characteristics in gastric cancer. Expression of FOXP3 mRNA and protein was found in four gastric cancer cell lines (AGS, SGC-7901, MKN-28 and MKN-45). IHC of the gastric cancer sections revealed that more than 56% of gastric cancers displayed nuclear or cytoplasmic FOXP3 staining. Furthermore, a linear relationship between the differentiation of the gastric cancer tissues and FOXP3 expression intensity was shown. IHC and confocal analysis showed that the expression of FOXP3 was mainly present in the nucleus of tumor cells in the tissues and cell lines. Thus, FOXP3 nuclear staining may be associated with the risk of poor tumor differentiation. Apart from the lymphocytes, no FOXP3 staining was noted in the normal gastric tissues and para-tumor tissues. The high frequency of FOXP3 expression in gastric cancer tissue is a significant finding in the investigation of tumor differentiation and immune escape. This mechanism provides a further understanding of gastric cancer and a novel therapeutic strategy is presented.

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