Expression And Significance Of FOXP3 In Normal Skin And Epidermis Neoplasms

Background:Increasing investigations indicated that the cancer patients'local and systemic imm-unologic function is in a state of tolerance or deficiency. And Tumor must escape from host immune surveillance for its further development. Regulatory T cells are unique T cell subgroups possessing the characteristic of immunosuppression and anergy, which are considerd as an important member of immunosuppressive network in tumors. CD4+ CD 25+FOXP3+ regulatory T cells (CD4+CD25+Treg) represent a main subset of regulatory T cells, which play a crucial role in the maintenance of immunological self tolerance and negative control of various immune response to non-self antigens. FOXP3 is a member of the forkhead-winged helix family of transcription factor, and has been demonstrated as a reliable marker of CD4+CD25+Treg.It plays a crucial role in the differentiation, development, and functionality of CD4+CD25+Treg.The overexpression of FOXP3+Treg has been found in tumors such as malignant melanoma, gastrointesti-nal tumors and breast cancer. And it is relevant with tumor stage and high mortality. However, studies to investigate the expression and significance of FOXP3 in normal skins and different epidermis neoplasms are few.Objective:To detect the expression of FOXP3 in lesions of seborrheic keratosis(SK), actinic keratosis(AK), Bowen's disease (BD), squamous cell carcinoma(SCC),as well as in normal skin controls; And to explore the significance of FOXP3 in normal,benign tumor lesions, precancerous lesions, malignant lesions of skin. Methods:1.73 cases diagnosed by clinic and pathology as epidermis neoplasms in the last ten years in the department of Dermatology of QiLu Hospital were collected, including 20 cases of seborrheic keratosis (SK),19 actinic keratosis (AK),21 Bowen's disease (BD),13 squamous cell carcinoma (SCC).As normal control,13 normal skin specimens obtained from clinic Operating Room and Plastic Surgery, were fixxed by formaldehyde and embedded by paraffin. As positive control, tonsil were getted from Pathology Room.2. The expression of Foxp3 in lesions of different epidermis neoplasms and normal skins was detected by immunohistochemistry technique.3. By using SPSS13.0 statistical analysis software, the expression of Foxp3 in normal skins and epidermis neoplasms was tested by Mann-Whitney test; One-way ANOVA was used to compare in groups of SK,AK,BD and SCC; Least-significant difference, LSD is applied ro pairwise comparison. The diference had statistical significance is P<0.05.Result:1. Location and distribution of FOXP3 in immunohistochemical stainFOXP3 mainly expresses in dermal lymphocytes. Buffy or darkbrown were observed which located in both nuclear and kytoplasm.FOXP3 positive lymphocytes were observed in partial cases of normal control, SK, AK, and BD. Lesions of all cases of SCC were infiltrated with FOXP3 positive cells, and the distribution of these cells was focal, In addition to dermis, FOXP3 positive lymphocytes were observed in epidermis.2. Positive label index of normal skins and different epidermis neoplasmsThe positive rate of FOXP3 positive lymphocytes in lesions of SK,AK,BD and SCC was higher than that in normal skin tissue (P<0.01). There was significant difference in the expression of FOXP3 among the SK,AK,BD and SCC lesions(P< 0.01). The positive rate of FOXP3-positive lymphocytes in AK lesions was higher than that in SK lesions(P<0.05). The positive rate of FOXP3-positive lymphocytes in BD and SCC lesions was both higher than that in AK lesions(P<0.05).But significant difference in the expression of FOXP3 between lesions of BD and SCC was not observed(P>0.05).Conclusion:1.Tumor infiltrating lymphocytes such as CD4, CD8, NK cells and other immune effector cells, to a certain extent, represent the body of the anti-tumor immune response, but there are a considerable number of excessive FOXP3+ lymphocytes, which may inhibit the effect of effector cell's function and reduce the role of its anti-tumor immunity.2. FOXP3 positive lymphocytes gradually increase in epidermis neoplasms from benign to malignant tumors. It may play an important role in immune escape of epidermal tumors and promotes their occurrence and development.3. Significant difference in the expression of FOXP3 between lesions of BD and SCC was not observed.It indicates that carcinoma in situ may already have some kind of immune regulation ability expressing or secreting chemokines to recruit an increasing number of FOXP3 positive lymphocytes and promote further development of cancer cells.