Expression Of KGF,KGFR,Bcl-2 In Oral Lichen Planus And Oral Squamous Cell Carcinoma

Objective:Oral Lichen Planus (OLP) is an autoimmune disease by T cell-mediated associated with chronic superficial inflammation. It was defined by the World Health Organization (WHO) as precancerous state. Various cytokines play an important role in the pathogenesis. The occurrence and cancerization of OLP were promoted by the interaction of the cytokines jointly. Oral squamous cell carcinoma (OSCC) is the most common oral cancer developed mostly from oral precancerous lesion or precancerous condition. The early diagnosis and treatment of precancerous lesions and precancerous conditions is contributed to the prevention of the OSCC. Keratinocyte growth factor (KGF) is the major growth factor secreted by the mesenchymal cells to promote keratinocyte growth. Keratinocyte growth factor receptor(KGFR) expresses mainly in epithelial cells, so KGF take the function of signal transmission between mesenchymal cells and epithelial cells. KGF not only has the function of anti-epithelial cell apoptosis and promoting epithelial cell proliferate and differentiate, but also has the potential capabilities of transformation, which relates to the occurrence of cancer. Bcl-2 belongs to a new class of cancer gene family members. It is an apoptosis regulatory gene studied deeply and extensively. Both OLP and OSCC are concerned with imbalance between apoptosis and proliferation in epithelial cell. So it is important to investigate the expression of KGFR, KGF, bcl-2 in OSCC and OLP for studying the pathogenesis, prevention and treatment of OLP and OSCC. Methods:20 OLP specimens who had not undergone any treatment were collected, including 8 cases of erosive OLP and 12 cases of non-erosive type.12 OSCC surgical resection specimens and 4 biopsy samples who had not undergone chemical and radiative treatment were collected, then graded according to the WHO standard for OSCC histological grading. Oral gingival tissues from removing impacted teeth and tissues around the benign lesions of 12 cases were set as control group. The tissues were fixed with 4% neutral formalin for 24 hours, embedded with paraffin, cut into 4μm thick serial sections and immunohistochemically stained with S-P methods using rabbit anti-human KGF polyclonal antibody (FGF-7/KGF), rabbit anti-human KGFR polyclonal antibody, rabbit anti-human bcl-2 monoclonal antibody. The positive staining showed as brown-yellow in cytoplasm or membrane. According to staining intensity and number of positive cells, the staining were divided into—,+,++ and +++, and scored correspondingly as 0,1,2,and 3. Each index in the normal epithelium, OLP tissue, OSCC tissue was compared with two sample rank test methods. Expression of KGF,KGFR and bcl-2 in the cancer were analyzed by Spearman correlation analysis. Statistical analysis was completed by SPSS 11.5 statistical software. Results:1.KGF expressed weakly in basal lamina of normal oral mucosa and OLP, positivly in submucosal muscle and vascular endothelial cells, and positivly in stromal cells of OSCC.2.KGFR expressed positivly in Basal layer and spinous layer of NOM, negatively or weakly positivly in the basal layer of non-erosive OLP, but showed as positive to intensive expression in basal layer, spinous layer and granular layer of erosive OLP (++～+++). particularly, epithelial peg stained deeply in two cases accompanied atypical hyperplasia of erosive OLP, even scattered expression was visible in stratum corneum. Expression of KGFR was weakly positive to intensive in OSCC cancer cells and stroma (range+～+++). Intensive staining distributed mainly in well-differentiated areas, particularly in well differentiated keratinizing cells.3. Bcl-2 expressed positivly in NOM epithelium, weakly positivly in the OLP epithelium and weakly positivly to intensivly in OSCC cells (range+-+++). Intensive staining distributed mainly in poor differentiated areas and diffused throughout the cancer nest. Statistically, expression of KGF was no significant difference between OLP and NOM, although increased slightly in OSCC than OLP and NOM, but there was no statistical significance, no significant difference as well as in well, moderate and poor differentiated OSCC. Expression of KGFR in non-erosive OLP, NOM and erosive OLP increased gradually, the difference was significant. There were significant differences of KGFR in well, moderate and poor differentiated OSCC also. The better OSCC differentiated, the stronger KGFR expressed; the poorer differentiated, the weaker expressed. Bcl-2 expression increased significantly in NOM epithelium than OLP, the difference was statistically significant. differences of Bcl-2 expression in well, moderate and poor differentiated OSCC were significant also, but contrary to KGFR, the poorer OSCC differentiated, the stronger bcl-2 expressed; the better differentiated, the weaker expressed. Expression of KGFR and bcl-2 in OSCC were correlated.Conclusion:1. KGF may not be the key role on the origination of OLP and OSCC.2.Expression of KGFR in non-erosive OLP, NOM and erosive OLP increased gradually. KGFR may be a important factor to influence proliferation of oral mucosal epithelial cell, which may be related to the pathogenesis of OLP and can be conducted to monitor OLP early canceration.3. Expression of bcl-2 in OLP epithelium decreased significantly than NOM epithelium, Which may be associated with increased apoptosis of epithelial cells and epithelial thinning in the OLP.4.Expression of KGFR,bcl-2 in well, moderate and poor differentiated OSCC were significantly different, which may be related to the differentiation of OSCC.5.Expression of bcl-2 and KGFR in OSCC were well correlated. Therefore, their combined applicaton will facilitate better accurate pathological grading of OSCC, which may be provide new diagnostic markers and therapeutic targets for clinical diagnosis and treatment of OSCC.