The Expression Of NDRG1 And Its Significance In The Carcinogenesis And Progression Of Uterine Cervical Squamous Cell Carcinoma

Objective: To study the expression and significance of NDRG1(N-myc downstream regulated gene-1)in the carcinogenesis and progression of Uterine cervical squamous cell carcinoma(UCSCC). Also to study the expression of tumor suppressor gene p53 and PTEN in UCSCC, and the correlation with NDRG1, for investigating the mechanism of NDRG1 expression.Methods: NDRG1 protein was detected by immunohistochemistry (IHC, ABC method) in 42 cases of UCSCC, 30 cases of high-grade squamous intraepithelial lesion (HSIL), 28 cases of low-grade squamous intraepithelial lesion (LSIL), and 20 cases of normal squamous epithelium. NDRG1 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in 10 cases of UCSCC and 10 cases of normal squamous epithelium. PTEN, p53 protein was detected by IHC (two-step method) in 42 cases of UCSCC and 20 cases of normal squamous epithelium.Results: The results of IHC shows that: From normal squamous epithelium to LSIL, HSIL and UCSCC, NDRG1 protein was gradually decreased during the tumor carcinogenesis (P=0.000),the positive ratio is separately 100%(20/20),92.9%(26/28),66.7%(20/30)and 52.4%(22/42).In UCSCC with non-lymphnode metastasis, the positive ratio of NDRG1 protein expression is 70.8%(17/24), and in UCSCC with lymphnode metastasis is dramatically decreased to 27.8%(5/18), There was inverse correlation of NDRG1 protein expression and metastatic conditions in UCSCC(R=-0.427,P<0.01). The relationship of NDRG1 with other clinicopathologic parameters has not been found, such as patients'age and tumor's differentiation degree. RT-PCR shows that: NDRG1 mRNA correspondence expression quantity was separately 1.21±0.13, 0.90±0.07 in normal squamous epithelium tissue and UCSCC tissue. The expression of NDRG1 mRNA was significantly lower in UCSCC than normal squamous epithelium(P=0.000). The positive ratio of PTEN expression in normal squamous epithelium and UCSCC was separately 75%(15/20)and 76.2%(18/42), the difference between them have no statistical significance(P>0.05). The positive ratio of p53 expression in normal squamous epithelium and UCSCC was separately 0%(0/20) and 54.8%(23/42). p53 was significantly up-regulated expression in UCSCC(P=0.000). The expression of p53 was inverse correlated with NDRG1(R= -0.483,P<0.01).Conclusion: Down-regulation of NDRG1 mRNA and protein in UCSCC maybe associate with its carcinogenesis and progression. NDRG1 gene was down-regulated in metastatic UCSCC, suggesting that NDRG1 maybe a potential biomarker for predicting metastasis of UCSCC. And NDRG1 gene maybe another downstream regulated gene of tumor suppressor gene p53 to suppress tumor growth and metastasis. PTEN gene may not be correlated with the carcinogenesis and progression of UCSCC.