Application Of Tissue Microarray Of Hpv Infection And Tumor-associated Gene Protein In Cervical Squamous Cell Carcinoma And Its Significance

Objective:To study the expression and significance of HPV16/18,31/33 DNA and P53,P16^INK4A, CyclinD1,and Ki67 proteins in invasive squamous cell carcinoma of cervix(ISCC),cervical intraepithelial neoplasia(CIN)and normal cervical epithelium(NCE).To investigate the correlation of HPV 16/18,31/33 DNA and proteins referred to above and the relationship between the biomarkers and clinical pathological parameters.To analyse the significance of the biomarkers in the occurrence and development of ISCC so as to provide the valuable evidence for the early clinical diagnosis an early therapy,and for the preservation of recurrence and metastasis of ISCC.Method:To make four,two,and two tissue microarrays embedded in 66 cases of ISCC,35 cases of CIN,and 30 cases of NCE respectively,in Situ Hybridization(ISH)was used to detect the expression of HPV16/18,31/33 DNA and the SP immunohistochemical method was performed to research the expression of p53,P16^INK4A,CyclinD1,and Ki67 protein in ISCC,CIN and NCE. Results was assessed by SPSS vision 12.5.Results:1.The positive expression rate of HPV16/18 in ISCC was markedly higher than in CIN and NCE(P＜0.05).No correlation was found between HPV16/18 and every clinical pathological parameters.There is no abvious difference about HPV31/33 expression in ISCC,CIN and NSE(P＞0.05),but the HPV31/33 positive expression was significantly high between lymph node transferation.and without lymph node transferation.2.The positive expression rate of P53 protein was 45.5%in ISCC,which was significantly higher than in NSE.There was difference about P53 protein expression between CIN and NSE.The positive rates of P53 protein expression were significantly higher in the cases of histological gradeⅢthan the cases of histological gradeⅠ-Ⅱand the cases with lymph node metastasis than those without lymph node metastasis(P＜0.001).3.The positive expression rate of P16^INK4Ahad the significant difference among ISCC,CIN and NSE.between ISCC and CIN,ISCC and NCE,and the difference was found between ISCC and NSE,between CIN and NSE.Significant relationship was observed between P16^INK4Aprotein expression and differentiated grades of the ISCC.4.We found the difference of the expression of CyclinD1 among ISCC,CIN and NSE.(P＜0.05).There was no difference between CyclinD1 and every clinical pathological parameter..5.Defference was significant about the positive expression of Ki67 among ISCC,CIN,and NSE.Significant relationship was observed between the positive expression of Ki67 and lymph node metastasis,and between the Ki67 expression and the invasion depth,too.6.We found the positive correlation between P53 and CyclinD1 protein, between Ki67 and P16^INK4Aprotein,and between Ki67 and P53 protein.Conclusion:There was a higher positive expression of HPV16/18 than that of HPV31/33 in ISCC and we found that mtp53 protein expression rate was very high because HPV DAN was positive in ISCC.The results of our study indicate that the positive expression rate of P16^INK4A,was high,but not low in ISCC.The positive expression of P16^INK4Ahint that P16^INK4Agenes might not act as a suppressor-gene only on the occurrence and development in ISCC.