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Comparison Of TGF-β1and N-cadeherin Expression In Oral Squamous Cell Carcinoma Of Human And Mouse And Observation Of Dtc In Submandibular Lymph Nodes In Mouse Oral Cancer Model

Posted on:2015-03-12Degree:MasterType:Thesis
Country:ChinaCandidate:B S WeiFull Text:PDF
GTID:2254330431953047Subject:Oral and Maxillofacial Surgery
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Objectives:1.To study the expression of TGF-β1and N-cadherin in normal oralmucosa, dysplasia, oral squamous cell carcinoma(OSCC) and metastatic lymphnodes tissue of human and mouse model.2.To detect the pan-CK positive cells in submandibular lymphnodes of normal oral mucosa, dysplasia and OSCC in mouse.Methods:1. The expression of TGF-β1and N-cadherin protein were detectedby Immunohistochemical staining in normal oral gingival tissues, dysplasiatissues, squamous cell carcinoma primary tumor tissues and neck lymph nodemetastasis carcinoma tissues, which from human specimens and Balb/c mouseoral squamous cell carcinoma model induced by4-NQO (4-nitroquinoline-1-oxide) in Drinking Water.2. Submandibular lymph node tissues of mouse model, which fromnormal oral mucosa group, oral dysplasia group and OSCC group, were stainedby pan-CK Antibody. Results:1. The expression rate of TGF-β1protein in human normal oralmucosa was33.3%(4/12), in oral dysplasia tissue was45.8%(11/24), in OSCCtissue was75.0%(18/24) and in lymph node metastasis was83.3%(10/12). Thelevel of TGF-β1expression in OSCC group and lymph node metastasis groupwas significantly higher than that in the normal group and oral dysplasia group(P<0.05). On the other hand, the expression rate of TGF-β1protein in mousenormal oral mucosa was22.2%(2/9), in oral dysplasia tissue was45.0%(9/20),in OSCC tissue was80.0%(16/20) and in lymph node metastasis was88.9%(8/9). The level of TGF-β1expression in mouse OSCC group and lymph nodemetastasis group was also significantly higher than that in the normal group andoral dysplasia group (P<0.05).2. The expression rate of N-cadherin protein in human normal oralmucosa was16.7%(2/12), in oral dysplasia tissue was45.8%(11/24), in OSCCtissue was79.2%(19/24) and in lymph node metastasis was83.3%(10/12). Thelevel of N-cadherin expression in human OSCC group and lymph nodemetastasis group was significantly higher than that in the normal group and oraldysplasia group (P<0.05). On the other hand, the expression rate of N-cadherinprotein in mouse normal oral mucosa was11.1%(1/9), in oral dysplasia tissuewas45.0%(9/20), in OSCC tissue was85.0%(17/20) and in lymph nodemetastasis was88.9%(8/9). The level of N-cadherin expression in OSCC groupand lymph node metastasis group was also significantly higher than that in thenormal group and oral dysplasia group (P<0.05).3. There was no pan-CK positive cell detected in normal mousesubmandibular lymph node tissue, whereas scattered pan-CK positive cells weredetected in submandibular lymph node tissue in2of8cases of mouse oral dysplasia group, and pan-CK positive cells cluster were found in2of4cases ofsubmandibular lymph tissue of mouse OSCC group without lymph nodemetastasis. The strong pan-CK positive expression cell masses were found in all4cases of submandibular lymph tissues from mouse OSCC group with lymphnode metastasis.Conclusions:1. The level of TGF-β1protein expression in OSCC and lymphnode metastasis tissue is significantly higher than the normal oral tissue and oraldysplasia tissue both in human and mouse, the expression shows an ascendingtendency among the different pathological degree of oral organization. Itsuggests that TGF-β1protein participated in the process of oral carcinogenesis,and plays a catalytic role in the development of EMT and tumor metastasis.2. The level of N-cadherin protein expression in OSCC and lymphnode metastasis is significantly higher than the normal oral tissue and oraldysplasia tissue both in human and mouse, the expression shows an ascendingtendency among the different pathological degree of oral organization. Itsuggests that N-cadherin protein, as an important biomarker of EMT, plays aimportant role in oral carcinogenic process and tumor metastasis.3. Pan-CK positive cell, which may be DTC, can be detected inthe local lymph node tissue when abnormally proliferate in the oral mucosa. Itindicates that the tumor cells may leave primary lesion in the very early periodeven precancerous lesions stage.
Keywords/Search Tags:Transforming growth factor beta1(TGF-β1), neural cadherin(N-cadherin), oral squamous cell carcinoma (OSCC), epithelial-mesenchymaltransition (EMT), pan-cytokeratin (pan-CK), disseminated tumor cell (DTC)
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