까le purpose of this study was to evaluate the role of EGF(Epidermal Growth Factor) , EGFR(Epidemlal Growth Factor Receptor), aFGF(acidic Fibroblast Growth Factor, FGF-1), bFGF(basic Fibroblast Growth Factor, FGF-2), FGFR(Fibroblast Growth Factor Receptor), and VEGF(Vascular Endothelial Growth Factor) 띠 the development of the oral squamous cell carcinoma. For this study 6 subjects, diagnosed as squamous cell carcinoma refelTed to the Dept. of Oral Path. College of Dentistry, Kyung Hee University, 2 subjects of normal 이띠 mucosa with any inflammatolY changes were used as expelimental, control groups respectively. AlI the 디ssu es ; expe디me nta l and control group were fixed in 100;ú neutral fOlmalin solution and embeclded in paraffìn , seIial tissue section were made 511m in thickness ancl processecl in the standard way for immunohistochemical methocl, using primary ancl seconclalY antibodies, for EGF(Antirabbit Ig G, rabbit kit at 1:100 dilution), EGFR(Antimouse Ig G, mouse kit at 1:100 dilution), aFGF(Antirabbit Ig G, rabbit kit at 1:100 dilution), bFGF(Antirabbit Ig G, rabbit 써t at 1:100 dilution), FGFR(Antimouse Ig G, mouse kit at 1:100 dilution), ancl VEGF(Antirabbit Ig G, rabbit kit at 1:100 clilution), all BioGenex U.S.A. macle, followed by the Stre ptavidin - Horse Radish Peroxidase(InnoGenex, Human-avidin kit) application, counter stained with Mayer’s hematoxylin stain method. And examined under the biologic microscope, -(no epithelial stain), +(weak or focal epithelial stain), ++(mode rate or focal intensive epithelial stain), +++(intense generalized epithelial staining) for the epithelial, and connective tissue component in squamous cell carcinoma and in nomlal mucosal epithelium on each. Attained results as follows ; 1. It is noted that more intensed reactio n EGF, EGFR, aFGF, bFGF, FGFR, and VEGF on experimental group compare to that on the control group. 2. Increased reaction is noted on the tumor components compare to that in the stromal tissues. 3. Intensed reaction is noted on the basement membrane adjacent to cancer nest to EGF, EGFR, aFGF, bFGF, FGFR, and VEGF 4. It is noted that intensed positive reaction on cancer pearls, cancer components with hyperactivities, in cancer nest. And at the peIiphelY of cancer nest, diffuse moclerate reaction to EGF, EGFR, aFGF, bFGF, FGFR, and VEGF is notecl This results suggest that EGF, EGFR, aFGF, bFGF, FGFR, and VEGF mJy be effectecl to the growth ancl clevelopment of the squamous cell carcinoma.
Matrix metalloproteinases(MMPs) are involved in the degradation of extracellular matrix, which is re lated to infiltrative growth and metastasis of tumor and are regulated by tisslle inhibitor of metalloproteinases(TIMPs) or cell adhesion molecllles such as E-cadherin and epidermal growth factor receptor (EGFR). The aim of this study is to evaluate the relationship between MMP-2, MMP-9 expressions and clinico-pathologic factors, 끼MP-1 ， TIMP-2, EGFR and E-cadherin expressions. lmmunohistochemical stains were perfom1ed on 55 cases of squamous cell carcinoma of the ordl cavity and the results were as follows. MMP-2 and MMP-9 expressions were noted in 30(54.5%) and 22(40.0%) of 55 cases, TIMP-1 and πMP-2 in 21(38.2%) and 33(60.0%), and E-cadherin and EGFR expressions in 35(63.6%) and 26(47.3%) of 55 cases, respectively. MMP-2 expression rdte was slightly higher 띠 cases without recurrence, and 끼MP- 2 expression rate was slightly higher in cases showing more inftltrative growth pattem. 까1e expression rate of EGFR was higher in cases with well differentiation(p=0.OO47), but no posi디ve relationship between the expression rate of Ecadherin and histologic grade was found. Cases with positive reaction for MMP-9 showed an increasing tendency of nega디ve reaction for TIMP-1. π1e expression rate of MMP-2 was higher in cases with positive reaction for E-cadherin and EGFR with no statistical significance. 까1e expression rate of MMP-9 was significantly higher in cases with positive reaction for E-cadherin(p=0.022l). These results suggest that MMP-2, MMP-9, TIMP-1 and TIMP-2 expressions are involved in the development of oral squamous cell carcinomas, but MMP-2, MMP-9, 끼MP-1 ， and 끼MP-2 expressions might not seem to be a useful prognostic factors because there were no significant relationship between clinicopathologic parameters. EGFR expression showed positive correlation with low histologic grade, so EGFR expression could be regarded as a good prognostic factor. In the progression of sqllamous cell
Alterations in cell surface receptors and adhesion molecules which regulate cell-cell and cell-matrix interactions have been 뻐plicated in tumor processes. In order to investigate the effect of integrin expression on the invasiveness of oral sqllamous cell carcinoma, integ띠1 expression in the celllines such as SCC-4, SCC-9, SCC-15, and SCC-25 was analyzed, and the comparison between cell adhesion assay towards extracellular matrix proteins and in vitro invasion assay following inhibition of the functional domain of the integrins using blocking antibodies against the specific integrins 낀 nd Arg-Gly-Asp (RGD) peptide were carried out. The expression of integrin a 2, a 3, a 6 was detected in all oral squamous cell carcinoma celllines. In contrast, the expression of a vß6 integrin is detected in SCC-4 and SCC-9, not in SCC-1 5 and SCC-25. 까1e adhesion of SCC-4 cell line to collagen 1, laminin, and fibronectin was significantly reducecl by σeatment with a 3-, a 6-, and a vß6-blocking antibody, respectively (p (0.05). 꺼.1e invasion of SCC-4 cell line throllgh Matrigel was significantly reduced by treatment with v 6-blocking antibody and RGD pepticle (p(0.05). These results sllggested that specifìc integrins play an in1portant role in the process of adhesion and invasion of oral squamous cell carcinoma cells and the expression of a vß6 integrin is believed to the enhance its invasivene잃.
To cletermine the role of mismatch repair in the clevelopment of oral squamolls cell carcinomas (OSCCs) , the prevalence of microsatellite instability (MSI), expression of I뼈LH1 ancll띠SH2 ， ancl hypennethylation of I뻐LH1 ancl hMSH2 were explorecl. Bya panel of five markers (BAT25, BAT26 , 02S123, 05S346, ancl 017~‘250 ， the so-callecl Bethescla markers) for screening of MSI, MSI was observecl in 5 of the 15 sqllamolls cell carcinomas (33.3%). As MSI is callsecl by the clysfllnction of MMR genes, this stucly examinecl the methylation status of CpG sites in the hMLH 1 ancl hMSH2 promoters ancl the expression hMLH1 ancl hMSH2. Becallse of inappr이)riate efficiency of fonnalin-frxecl ancl paraffin-embeclclecl samples for methylation-specific PCR (MS-PCR) of hMLH1 ancl hMSH2, the role of promoter hypelmethylation 띠 the clevelopment of MSI ancl expression of hMLH1 ancl hMSH2. meùlylation was failecl to clefìne. However, loss of nllclear staining of 1ψIILH 1 ancl hMSH2 were seen in nine (69.2%) ancl four (30.7%) of 13 OSCCs, while four ancl fìve all corresponcling normal epiùlelial tisslles showecl positive nllclear stι ining ofl마ILH1 and hMSH2. These data suggest that MSI anclloss of expression of hMLH1 ancl hMSH2 play a role in the carcinc핑enesis of oral sqllamolls cell carcinomas thollgh the role of promoter hypermethylation of hMLH1 ancl hMSH2 in MSI and their expresslon IS lIncertam
Transglutaminase 2(TGase 2) expression is modulatecl by π>JF- a in various carcinoma. The role of TGase 2 ancl TNF- a expression in salivaIY gland tumors is not clear yet. Establishecl SGT cellline has been used to study the pathogenesis of salivaIY gland adenocaI‘cinoma on a cellular level in vitro. 까le pupose of this study were to examine n버NA expression of TGase 2 and TNF- ain SGT cellline comparecl to other tumor celllines, ancl to apply these results to the paùlogenesis of salivary gland tumor. After SGT, SCC-15, HN 4, and HeLa tumor celllines were culturecl under preconfluency, ancl 3 clays after postconfluency, the cells were harvested for total RNA extraction and cDNA preparation. RT-PCR for semiquantitative mRNA analysis was done. 까le obtained results were as follows. 1. TGase 2 and π>JF- amRNA expression was not induced by confluency in all the celllines 2. TGase 2 and π'JF- amRNA expression was variable but markeclly enhanced 비 SGTcellline 3. TGase 2 n버NA expression appeared to be associated with that of π>JF- ain SGT cellline From the aboving res ults, mRNA expression of TGase 2 and TNF a should play an important role in the pathogenesis of SGT cellline originated ti'om ductal cell.
Squamous cell carcinoma comprises about 95% of oral cancers. 까le gene디C 없mage in carcinogen-exposed fields is accumulated to transforrn norrnal mucosa in dysplas디c tissue and fmally invasive carcinoma through multistep process. This carcinogenic process has been a cause of the development of secondary tumors after the removal of primary carcmoma. πle improvement of therapeutic modalities of oral cancer has driven into the increase of multiple cancer occurrence in head and neck region. We experienced 3 pa디ents who had mul디ple squamous cell carcinomas in oral cavlty. π1ÎS study aimed to report multiple pr따laπ squamous cell carcinoma by clinical and pathologic examination and to discuss their molecular mechanism