| Cervical cancer is the third most commonly diagnosed cancer in females worldwide, and the incidence of cervical cancer is getting younger and younger and rising. The main reason of the incidence of cervical cancer is persistent infection of high risk HPV, but its development, recurrence and metastasis processes are very complex. Treatment effect and prognosis are not optimistic in part patients, so it has become a hot study topic. Vasculogenic mimicry(VM), hypoxiainducible factor-1α(HIF-1α) and EMT(epithelial-mesenchymal transition, EMT) are prevalent existing in highly malignant tumors, and they play important roles in the genesis and development of tumors, including cervical cancer.Being different from traditional vascular endothelium, VM is a kind of irregular pipe-like channel, which is directly surrounded by tumor cells, while not endothelial cells(CD34-negative). Inside the channel, there is one layer of PAS-positive basement membrane and sometimes red blood cells, being not with obvious inflammatory cells and necrotic cells. And the channel is communicating with peripheral vasculars. The structural characteristics of VM determine that tumor cells without barrier function of the endothelial cells more easily penetrate the basement membrane into the blood circulation and metastasis in this microenvironment. HIF-1α plays an important role in adapting to hypoxic microenvironment and angiogenesis of tumors. EMT, the process of epithelial cells into mesenchymal cells transition, makes the tumor cells looser in morphology, leading tumor cells are more prone to metastasis. Epithelial phenotype Ecadherin losing and mesenchymal phenotype Vimentin obtaining were regarded as the signs of EMT process. Rapid growth of tumor cells can result in the formation of hypoxic microenvironment surrounding the tumor, and it will increase the expression of HIF-1α, which then contributing to the formation of VM by inducing EMT with E-cadherin losing and Vimentin obtaining. All of HIF-1α, EMT and VM can promote the development of cervical cancer, but the studies about the latter two are still few. This article aims to explore VM, HIF-1α and EMTassociated marker proteins, E-cadherin and Vimentin, expressions in human cervical squamous cell carcinoma(HCSCC) and their relationships and significances.In this study, 43 parafin specimens of HCSCC and 20 paraffin specimens of normal cervical tissues were collected; hematoxylin and eosin staining and immunohistochemical double staining of CD34 and PAS was used to detect the presence situation of VM; immunohistochemical method was used to detect the expression characteristics of HIF-1α, E-caherin and Vimentin proteins in HCSCC. In the results we found that the positive rate of VM group in HCSCC was 37.2%(16/43), which was significantly higher than that in normal cervix group(P<0.05); the positive rate of VM in poorly differentiated HCSCC(56.5%) was significantly higher than that in moderately and well differentiated HCSCC(15.0%), and it was related to FIGO stage, lymph node metastasis and thrombus formation(P<0.05); there was significant differences in positive expression rates of HIF-1α, E-cadherin and Vimentin between HCSCC and normal cervical tissues, they were 60.9% and 20.0%, 37.5% and 100.0%, 32.8% and 0 respectively(P<0.05); the expression of HIF-1α was related to tumor size, pathological grade and lymph node metastasis or not(P<0.05), the expression E-cadherin appeared significant differences with the different pathological grade of HCSCC(P<0.05), and the expression of Vimentin was related to pathological grade, lymph node metastasis or not and thrombus formation or not(P<0.05); there was negative correlation between E-cadherin expression and Vimentin expression(r=-0.330, P<0.05), there were respectively positive, negative and positive correlations between VM expression and HIF-1α, E-cadherin and Vimentin expressions(r respectively=0.426,-0.394, 0.697, P all<0.05), and there were respectively negative and positive correlations between HIF-1α expression and E-cadherin and Vimentin expressions(r respectively=-0.362, 0.359, P all<0.05); in the serial sections for localization immunolocalization, the HIF-1α expression was correlated with negative of E-cadherin and positive Vimentin in 56.2%(9/16)of VM-positive patients, but a correlation was not found in VM-negative HCSCC samples(P<0.05). These show that VM exsists in HCSCC tissues, and the expressions of VM, HIF-1α, E-cadherin and Vimentin are all closely correlated with malignant progression of HCSCC; HIF-1α may induce EMT by down-regulation of E-cadherin and upregulation of Vimentin expressions, and they may promote the formation of VM in HCSCC tisues; the combined detection of VM, HIF-1α, E-cadherin and Vimentin may have an instructive role in predicting the progression, prognosis and clinical diagnosis and treatment of HCSCC. |
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