Expression Of PTEN HIF-1α VEGF Laryngeal Quamous Cell Carcinoma And Their Clinical Significance

BacgroundLaryngeal carcinoma is a common malignant tumor in otolaryngology-head and neck surgery.Laryngeal squamous cell carcinomas comprise the vast majority(96%) of laryngeal malignancies and increasing has been observed in recent years.The complex molecular mechaniams in the malignant transformation and progression of laryngeal carcinoma have still not been well understood like other tumors.However,with the rapid development of tumor molecular biology it has been demonstrated that the occurrence of tumor was a long term,multiple factors,and grading process. Oncogene's activation and tumor suppressor gene's inactivation were considered to be closely related to laryngeal carcinoma.PTEN is a novel tyrosinephosphatase antioncogene.HIF-1αis a major transform factor under hypoxia,which regulates the protein VEGF.Now little is known about the relationship between the expression of PTEN,HIF-1αand VEGF proteins and tumorigenesis,differentiation,biological behavior and outcome of laryngeal squamous cell carcinoma(LSCC).In order to analyze the relationship between the clinicopathological features and the expression of PTEN,HIF-1αand VEGF proteins,we detected the expression of PTEN,HIF-1αand VEGF proteins by immunohistochemical method.This research discuss the probable disease mechism and influence factors of prognosis of LSCC from the epidemic and pathology angle,which provide lab evidence for directing clinic therapy,aidnosising diagnosis and judging prognosis of LSCC.Materials and Methods1. PatientsIn this stidy, All of the clinic datas were whole,and they were not treated by any chemotherapy and radiotherapy before undergoing the peration.All pathologic diagnoses were laryngeal squamous cell carcinoma.2. Method and Evaluation of ImmunostainingThe expression of PTEN,HIF-1αand VEGF proteins was detected by immunohistochemical method.Clearly brown staining restricted to cytoplasm was considered as positive expression of PTEN protein.Clearly brown staining restricted to cytoplasm or nucleus was considered as positive expression of HIF-1αprotein.Clearly brown staining restricted to cytoplasm was considered as positive expression of VEGF protein.3. Statistical AnalysisSPSS13.0 software was employed to analyze all data.Statistical evaluation was performed using Chi-Square test.P<0.05 was considered as statistical significance.Results1. PTEN protein was mainly restricted to cytoplasm. The positive rate of protein expression in the cases of laryngeal carcinoma was 61.40%,and in the normal tissue cases was 100%. By being compared them,the difference was statistically significant(P<0.05). The positive rate of PTEN protein expression in the well-differentiated LSCC was 84.85%,while in the moderately and poorly differentiated was 29.16%. Also compared in the different clinic stage,the positive rate of the group of stage I～II was 81.48%,while stageIII～IV was 43.33%.The differences were statistically significant(P<0.01). Being compared with the group with lymph node metastasis(40.91%),the positive rate of the relative group(74.29%) was significantly different(P<0.05). 2. HIE-1αprotein was mainly restricted to cytolymph and partially interstitial tissue.Compared between in the LSCC tissue(78.95%) and normal(20.00%),the positive rates of expression were significantly different(P<0.01).Of stage I～II and stageIII～IV,the rates were sperately 62.96%,93.33%. The differences were statistically significant(P<0.01). And of the group with lymph node metastasis and the group without lymph node metastasis,they were 95.45%,68.57%.The differences were statistically significant(P<0.05).3. VEGF protein was restricted to cytolymph,also periplast and vascular endothelial cell. Compared between in the LSCC tissue(75.43%) and normal(20.00%),the positive rates of expression were significantly different(P< 0.01).In the well-differentiated LSCC, The positive rate was 63.63%.In the moderately and poorly differentiated,it was 91.66%. And of the group with lymph node metastasis and the group without lymph node metastasis,they were 95.45%,68.57%.Both the differences were statistically significant(P<0.05).4. The positive expression group of PTEN protein and negative group in laryngeal squamous cell carcinoma,the positive expression rates of HIF-1αwere 68.57% and 94.45% respectively,a significant difference between them(contingency coefficient r=0.306,P<0.05). The positive expression group of HIF-1αprotein and negative group in laryngeal squamous cell carcinoma,the positive expression rates of VEGF were 84.44% and 41.67% respectively,a significant difference between them(r=0.376,P<0.01).Conclusion1. There is loss-expression or lower-expression of PTEN while higher-expression of HIF-1αand VEGF in the tumor tissue.It speculates three protein play a certain role in the tumorigensis and development of laryngeal squamous cell carcinoma.2. The expression of PTEN protein has closely correlation with evolvement of clinic stage and pathologic grade,also lymph node metastasis of LSCC.With the lower-expression of PTEN,the clinic stage is higher and the differentiation is more perfect,the PTEN expression of thegroup with lymph node metastasis is lower than the group without lymph node metastasis. This demonstrates that the level of inactivation and/or deletion of PTEN is increasing with the development of LSCC,and contribute to the metastasis.It may be estimated that the inactivation and/or deletion of PTEN is one of the mechanism of LSCC.3. The expression of HIF-1αprotein is closely related to the evolvement of clinic stage and lymph node metastasis of LSCC.With the increased expression of HIF-1αprotein,the clinic grade is higher.It is higher expression in the group with lymph node metastasis than without.All hint the high-expression of HIF-1αprotein contributes to the invasion and metastasis of LSCC.4. The expression of VEGF protein is closely related to the evolvement of pathologic grade and lymph node metastasis of LSCC.LSCC which is more malignant and higher expression of VEGF has lower pathological cell differentiation.And It is higher in the group with lymph node metastasis than without lymph node metastasis.It demonstrated that VEGF may play a important role in the development and metastasis of LSCC.5. PTEN,HIF-1αand VEGF may respectively take part in the progression of LSCC.And there is a certain relationship in three proteins.The level of inactivation and/or deletion of PTEN may deprivat the down-regulation of PI3K/Akt and enhance the expression of HIF-1α.Then HIF-1αinduces angionenesis by up-regulate the expression of VEGF.