Expression And Significance Of CD44V6, MUC1 Before And After Neoadjuvant Chemotherapy In Cervical Cancer

Background and ObjectiveCervical cancer, which is one of the common gynecological malignant tumors, has the first incidence rate. In our country the morbidity and mortality of cervical cancer shows an increasing trend in recent years. Since Frei proposed the program of Neoadjuvant Chemotherapy(NACT)in 1982, it has been used in clinic more and more. Not only can NACT reduce the size of the tumor, increase the operability, and enhance the sensitivity of the tumor sell to radiotherapy, but also can decrease the occurrence of metastasis, reduce the risk of recrudescence and enhance the survival rate. Now the clinical short-term curative effect of NACT has been well proved by most researches, but it still has some patients who have poor sensitivity to chemotherapy. Enforcing NACT to these patients can delay the best time for the other treatments. Therefore, it is of great significance to searching the index which can predict the effect of NACT exactly.CD44, which calls eluster of differentiation 44, is a widespread transmembrane glycoprote on the cell surface.It belongs to cellular adhesion molecule. CD44 can be divided into:standard CD44(CD44S) and variant CD44(CD44V). In variant CD44, CD44V6 has a close relationship with the tumor. The tumor cell which has a high expression of CD44V6 can adhere to the extracellular matrix (ECM), give the tumor cell a high invasive ability, and compose the invasion and metastasis of the tumor cell thereby. Mucoprotein 1(MUC1)is a glucoprotein with high molecular mass. It plays an important role in protecting normal epithelial tissue. In tumor, MUC1 expresses abnormally. It expresses abundantly and the heteropolarity is disappeared. It disturbs the function of adhesion molecule of the whole tumor cell surface and reduces the adhesive ability between tumor cells. It takes part in the invasion and metastasis and has a close connection with the development of the tumor.Cell adhesion is the initiating factor to the invasion and metastasis of tumor. The abnormal expression of cell adhesion molecules is closely related to the invasion and metastasis of tumor. So far, the researches about predicting the efficacy of NACT of cervical cancer mostly focus on the proliferation and apoptosis mechanisms of cells, but it is rarely reported about CD44V6 and MUC1 in this field. Through detecting the expression of CD44V6 and MUC1 before and after NACT of cervical cancer, this study evaluated the curative effect of NACT, discussed the correlation between the clinical effect and the clinical pathological factors, and explored the feasibility of CD44V6 and MUC1 being the index of effective prediction. The purpose of this study was to find out the sensitive index for predicting the effect of NACT, and provide guidance for the application of NACT in clinical practice.Material and Methods1. Clinical dataThe paraffin section came from the department of pathology in the Second Affiliated Hospital of Zhengzhou University. All the cases were identified by histopathologic examination and had no other therapy before NACT. In this study we collected forty cervical biopsy specimens before NACT and forty surgical specimens after NACT. The chemotherapy plan was TC (Paclitaxel+Carboplatin) programe.2. Experimental methodImmunohistochemical (IHC) staining was used to examine the expression of CD44V6 and MUC1 in cervical cancer before and after NACT. 3. Statistics analysisStatistical analysis was executed by statistical package SPSS version 10.0 software. The statistic data were analyzed with Chi-square tests and Fisher's exact probability test. Pearson correlation analysis was used to analyze correlation between CD44V6 and MUC1, and a value less than 0.05 was considered as significance.Results1. Clinical effectThe overall response rate of NACT was 85%, including CR group 4(10%), PR group 30(75%) and SD group 6(5%). There was no PD samples, and 100% of patients had operation.1 case with stageâ…¡was confirmed as cervical squamous cell carcinomas in situ by pathological examination after the surgery.2. The expression of CD44V6 and MUC1The positive expression of CD44V6 and MUC1 in cervical cancer after NACT was significantly lower than that before NACT. There was significant difference between the two groups (P<0.05). In clinical effective group the positive expression of CD44V6 and MUC1 after NACT was significantly lower than that before NACT, and the difference had statistical significance (P<0.05); The positive expression of CD44V6 and MUC1 before and after NACT in clinical invalid group had no obvious contrast(P>0.05). The contrast of the positive expression of CD44V6 and MUC1 between the clinical effective and invalid groups before NACT had no statistical sense (P>0.05). Before NACT the metastatic rate of lymph nodes in group with CD44V6 and MUC1 positive expression was significantly higher than those in the negative group (P<0.05). In cervical cancer tissues with different pathologic type, clinical stage and histological grade, the change of positive expression of CD44V6 and MUC1 before and after NACT has no significance (P>0.05).3. The correlation between CD44V6 and MUC1 in cervical cancerIn the expression of CD44V6 and MUC1 before NACT in 40 cervical cancer tissues, the positive co-expression had 22 cases, and the negative co-expression had 8 cases. There was positive correlation between the two groups (P<0.05, r=0.409). In the expression of CD44V6 and MUC1 after NACT in 40 cervical cancer tissues, the positive co-expression had 10 cases, and the negative co-expression had 18 cases. There was positive correlation between the two groups (P<0.05, r=0.354).Conclusions1. The neoadjuvant chemotherapy TC program has good short-term curative effect on cervical cancer, and it is worthwhile for extensive application.2. Detecting the expression of CD44V6 and MUC1 before NACT in the cervical cancer tissues can not predict the curative effect of NACT.3. Detecting the expression of CD44V6 and MUC1 after NACT in the cervical cancer tissues can better evaluate the curative effect of NACT. It can be considered as clinical effective group if the expression of CD44V6 and MUC1 had obvious declined after NACT.4. In cervical cancer tissues, there is positive correlation between CD44V6 and MUC1. The combined detection of CD44V6 and MUC1 can evaluate the effect of NACT better.5. The expression of cellular adhesive molecular decline obviously after NACT. It may have positive effects on improving the prognosis of cervical cancer.