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The Expression and Significance of PhosPhatas of Regenerating Liver-3 and Matrix Metalloproteinase-14 and CD105 in Human Laryngeal Squamous Cell Carcinoma

Author: HuHaiLi
Tutor: DongXueLei
School: Zhengzhou University
Course: Otorhinolaryngology
Keywords: PRL-3 MMP-14 MVD CD105 LSCC
CLC: R739.65
Type: Master's thesis
Year: 2011
Downloads: 29
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Abstract


Laryngeal squamous cell carcinoma is one of common malignant tumors in head and neck,95%-98% of Laryngeal cancer is squamous cell carcinoma. Whose therapy is mainly radical surgery combined with radiotherapy or precise radiotherapy, patients in early stage may obtain better local control rate, but metastasis can not be prevented or reduced, for sufferer in middle or late stage, conventional therapy is not so satisfactory,the local recurrence rate is about 27-61%, the metastas rate is 18-21%, and the five-year survival rate is 27-34%.With the development of tumor biology, many new technologies are servced for the clinical,but in practice, many effects and results can not be explained now.For Head and neck tumors, the main factors that affect patient survival are invasion and metastasis,but the mechanisms that the invasion from primarily focus to perienchyma even metastasis and malignant cells obtain invasion ability are still unclear, to clarify the mechanisms and improve the prognosis of patients with laryngeal cancer, It is important to explore new and specific tumor marker. Phatase of regenerating liver-3(PRL-3) is a newly discovered protein tyrosine phosphatase, belonging to protein tyrosine phosphatase. it can regulate protein function by dephosphorylation, and is involved in various cellular life activities, research shows that PRL-3 is involved in invasion and metastasis of many tumors by promoting cell proliferation, migration, invasion, adhesion and angiogenes.Matrix metalloproteinase-14(MMP-14) belonging to membrane-type matrix metalloproteinases is a kind of transmembrane protein. It can degrade extracellular matrix, which is one of the conditions to the formation of malignant tumors.CD105, also called endoglin, is a glycoprotein, it mainly locats in nascent vascular endothelial cell membrane and cytoplasm, but not in large vessel.so it is an ideal marker of endothelial cells,CD105-MVD is the gold standard of tumor microvascular density.At home and abroad, the research on PRL-3 focused on glandular carcinoma,but the study in laryngeal squamous cell carcinoma has not been reported.The roles of PRL-3 in tumor invasion and metastasis are not clear, it was reported PRL-3 might be involved in tumor invasion and metastasis by matrix metalloproteinase and angiogenesis pathway, but the expresssion of PRL-3, MMP-14 and CD105 and their relationship with laryngeal squamous Carcinoma has not been reported.ObjectiveTo explore the Relationship beween human laryngeal carcinoma invasion and metastasis with PRL-3, MMP-14,and find the tumor markers that may predict invasion and metastasis laryngeal squamous Carcinoma, further to supply the helpful observation index for the patients and the theoretical evidences for the advanced study,the expression levels of PRL-3,MMP-14 in laryngeal squamous cell carcinomwere are detected by immunohistochemistry and microvessel density (CD 105-MVD)of tumor tissue is labeled with CD105.Materials and methods1. Research objectparaffin blocks of tissue samples from 69 Human laryngeal squamous cell carcinoma patients in the First Affiliated Hospital of Zhengzhou University between January 2006 and December 2008 were collected, of which 28 cases were well-differentiated,41 were low-differentiated,and 25 cases were lymph node metastasis positive,44 cases were negtive. According to international UICC cancer association (TNM classification criteria) (2002):I period stage:11 cases,Ⅱperiod: 15 cases,27 cases, III period IV stage:16 cases, age of The Patients is beween 40 and 84 years old (average 62 years old), male 67 and female 2, the clinical data of all patients were complete, none received radiation and chemotherapy and any immunotherapy before operation. the same batch adjacent cancer mucosal tissue from 35 patients and 32 cases normal throat mucosal tissue were also collected as the control, the length beween the place that adjacent cancer mucosal tissue were collected and the tumor edge more than 1.0cm, all confirmed as squamous epithelial cells atypical hyperplasia by pathology, Cancer cells were not found.2.MethodsThe Expression of PRL-3 and MMP-14 in samples of 69 Human laryngeal squamous cell carcinoma and 35 Corresponding adjacent cancer mucosal tissue and 32 normal throat mucosal tissues by immunohistochemistry respectively, microvessel density (CD105-MVD) of tumor tissue is labeled with CD 105. to explore the relationship between PRL-3 and CD 105-MVD,the results were analyzed with clinicopathologic factors.3.Statistical treatmentThe data were recorded and analyzed by SPSS18.0 package, measurement data were recorded as x±s The rates and means between each group were respectively analyzed by x2 test and t test, the relationship beween PRL-3 and MMP-14 CD105-MVD were tested by Spearman rank correlation analysis, with a= 0.05 as inspective standards.Resultsl.The positive rate of PRL-3 in laryngeal Squamous Cell carcinoma(65.22%) was higher than that in adjacent tissues(17.17%) and normal tissues(15.63%),the difference is significant (P<0.01). the expression of PRL-3 in lymph-node metastasis group is significantly higher than in no-metastasis group, the difference is significant (P<0.05). the expression of PRL-3 inⅢ～Ⅳstage is significantly higher than that in stageⅠ-Ⅱ(P<0.05). The expression of PRL-3 is positively correlation with lymph-node metastasis, pathological stage and differentiation degree.But has no correlation with primarily focus. gender and age.2.The positive rate of MMP-14 in laryngeal Squamous Cell carcinoma(76.81%) was higher than that in adjacent tissues(31.43%)and normal tissues(25.00%),the difference is significant (P<0.01). the expression of MMP-14 in lymph-node metastasis group was significantly higher than in no-metastasis group, the difference is significant (P<0.05). the expression of MMP-14(P<0.05) in pathological stageⅢ～IV was significantly higher than that in stageⅠ-Ⅱ(P<0.05). The expression of MMP-14 is positively correlation with lymph-node and pathological stage and differentiation degree.But the expression of MMP-14 have no correlation with primarily focus, gender and age.3.CD105-MVD in lymph-node metastasis group (13.4000±4.36845) is significantly higher than that in no-metastasis group (10.7273±4.08835) the difference is significant (P<0.05). CD105-MVD inⅢ-Ⅳpathological stage (12.7907±4.16080) is significantly higher than that in stageⅠ-Ⅱ(9.8846±4.13112),(P<0.05).CD105-MVD is positively correlation with lymph-node and pathological stage,But no correlation with differentiation degree, primarily focus and gender and age.4.The expression of PRL-3 and MMP-14 are positively correlation with CD105-MVD (respectively rs=0.811 and r,=0.867, both P<0.0).5.The difference beween the positive rate of PRL-3 and MMP-14 is not statistically significant, but the expression of PRL-3 is positively correlation with that of MMP-14.Conclusions1.PRL-3 and MMP-14 are involved in invasion and metastasis of laryngeal squamous cell carcinoma,and may play important roles in the diagnosis of laryngeal squamous cell carcinoma. 2.PRL-3 and MMP-14 was positively correlated.They promote tumor angiogenesis and can be combined as the marker laryngeal squamous cell carcinoma,they may play an important role in the options of clinical treatment and prognosis assessment.3.CD 105 is an ideal marker of tumor angiogenesis,CD105-MVD could be assessed as an important indicator of metastasis and prognosis of laryngeal squamous cell carcinoma.4.PRL-3, MMP-14 is closely related with tumor angiogenesis and play an important role in laryngeal squamous cell carcinoma.

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