Expression Of CK10 And CK17 In Cervical Lesion And Its Prognostic Value In Early Cervical Cancer

Cervical Cancer?CC?is one of the most common gynecological malignant tumors worldwide.The high incidence age is 50-55 years old.In recent years,with the popularization of cervical cancer screening,cervical cancer can be detected and treated early,and its morbidity and mortality have decreased significantly.Relevant literatures reported that 528,000 people suffered from diseases and 266,000 died in the world in 2012,ranking fourth in the incidence and mortality of female malignant tumors^[1].In 2013,there were 100,700 cases of cervical cancer and 26,400 deaths in China.The incidence and mortality of cervical cancer were younger and rising gradually^[2].For the treatment of cervical cancer patients clinically,appropriate individualized treatment plans are often formulated after comprehensive consideration of clinical stages,reproductive needs,age and medical level of patients.The preferred treatment for patients with advanced cervical cancer is radiotherapy and chemotherapy.However,because of the special location of cervical lesion and easy infiltration of surrounding tissues,the recurrence rate and metastasis rate are high,and the prognosis is not good.The 5-year survival rate of patients is low^[3].It has been reported that the 5-year survival rate of patients with advanced cervical cancer is about 55.33%to 68.81%^[4].Early cervical cancer patients are mainly treated with surgery,supplemented by radiotherapy and chemotherapy,and have a good prognosis,but some patients also have rapid disease progression and poor prognosis.It has been reported in the literature that the clinical pathological characteristics of cervical cancer patients under 35 years old are late clinical stage and high degree of malignancy,with many influencing factors and poor prognosis^[5].Currently,there are few molecular markers available to evaluate the progression of early cervical cancer and predict the prognosis of patients with early cervical cancer.Therefore,it has become a persistent pursuit of gynecological oncologists to search for a molecular marker to predict the prognosis of patients with early cervical cancer.Cytokeratins?CK?is a kind of intermediate filament protein of cytoskeleton,which is usually located in the cytoplasm of epithelial tissue.At present,54genotypes have been found in human,but more than 20 genotypes have been found earlier.Cytokeratin is expressed differently in epithelial cells of different organs or tissues and at different stages of cell differentiation^[6].It can provide a framework for epithelial cells and tissues to maintain the integrity of cells and tissues,and at the same time,plays an important role in malignant transformation of epithelial cells,various stress reactions and apoptosis tolerance^[7].Cytokeratin has Specific expression in cancer tissues,a relevant literatureit has been reported that:When invasive tumors occur,AKT/mTOR pathway is activated,which regulates the development of epithelial tumors.When AKT2 was overexpressed,the expression level of cell keratin 18 increased.When AKT1 was overexpressed,the expression level of cell keratin 8/18 increased^[8].The expression of keratin in normal and diseased tissues can be detected by immunohistochemistry,and when the cell keratin fragments are dissolved,the dissolved fragments can be detected in the blood,The overexpression of keratin in tumor tissues may provide diagnostic and prognostic value for tumor patients^[9],Such as:CK17 is highly expressed in oral squamous cell carcinoma and significantly correlated with the prognosis of patients^[10].The expression of CK20 in lymph nodes of patients with rectal cancer was significantly correlated with the prognosis of patients with rectal cancer^[11].The expression levels of CK18 and CK19 are negatively correlated with the severity of prostate cancer,which is of guiding significance for the prognosis of prostate cancer patients^[12].High expression of CK5/6 in breast cancer tissues is a poor prognostic factor for breast cancer patients^[13].In cervical cancer,CK10 is highly expressed in normal cervical tissue but not or lowly expressed in cancer tissue,and the expression level of CK10may be positively correlated with the differentiation of cancer tissue.The higher the differentiation of cancer tissue,the higher the positive expression rate of CK10.CK17 is not expressed in normal tissues but is highly expressed in cancer tissues^[8].However,there are no articles about predicting the prognosis of patients with cervical cancer with CK17 and CK10.Objective1.To study the expression of CK10 and CK17 in normal cervical tissue,cervical squamous intraepithelial lesion?SIL?and early cervical cancer,and to explore the correlation between CK10 and CK17 and the severity of cervical lesions.2.To explore the correlation between CK10 and CK17 and the prognosis of early cervical cancer patients.Materials and methods1.Clinical dataA total of 240 cases of cervical tissue resection were collected from the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2013.Among them,60 cases were normal cervical tissue,Material taken from uterine myoma?fibroid?patients undergoing total hysterectomy and pathologically confirmed cervical lesion-free;60 cases were cervical squamous intraepithelial lesions?SIL?,including low-grade and high-grade squamous intraepithelial lesions,There were 30 cases of LSIL and 30 cases of HSIL,Samples were taken from patients with abnormal TCT and HPV infection who underwent cervical biopsy and confirmed by pathology after operation.120 patients with early cervical cancer?IA-IIA1?were included in the study,and the inclusion criteria were:all patients were newly diagnosed,meeting the clinical diagnostic criteria for cervical cancer,without any radiotherapy or chemotherapy before the surgery,and finally underwent radical surgery.2.Test methodsThe positive rates of CK10 and CK17 in normal cervical tissues,LSIL,HSIL and early cervical cancer were detected by immunohistochemical SP method.The correlation between CK10 and CK17 and the severity of cervical lesions was analyzed.To investigate its relationship with the clinicopathological characteristics of patients with early cervical cancer and its value in predicting the prognosis of early cervical cancer.3.Statistical methodsSPSS 21.0 was used for statistical analysis.The qualitative data were compared by x² test.Spearman grade correlation analysis was used for the correlation between severity of cervical lesions,?=0.05,as the test level,P<0.05 was statistically significant.Kaplan-meier survival curve method,univariate analysis and Cox proportional risk regression model were used to analyze the influence of CK10 and CK17 on the prognosis of patients with early cervical cancer.Results1.Expression of CK10 and CK17The positive expression rates of CK10 in normal cervical tissues,SIL and cervical cancer were 80.00%,50.00%and 21.67%,respectively.There was significant difference among the three groups?x²=56.878,P<0.001?.The positive rate in normal group was higher than that in SIL group,x²=11.868,P=0.001;in SIL group,it was higher than that in cervical cancer group,x²==14.983,P<0.001;in normal group,it was higher than that in cervical cancer group,x²=56.221,P<0.001.Intra-SIL comparison,the positive expression rates of CK10 in LSIL and HSIL in SIL group were 66.67%and 33.33%respectively,x²=6.667,P=0.01,with statistical significance.The positive rate of CK10 was negatively correlated with the severity of cervical lesions?r=-0.484,P<0.001?.The positive expression rates of CK17 in normal cervical tissue,SIL and cervical cancer were 0%,46.67%and 80.00%,respectively.Significant?x²=103.315,P<0.001?.Two or two comparisons among three groups:the positive rate of SIL group was higher than that of normal group,x²=36.522,P<0.001;the positive rate of cervical cancer group was higher than that of SIL group,x²=20.737,P<0.001;the positive rate of cervical cancer group was higher than that of normal group,x²=102.857,P<0.001.Intra-sil comparison,the positive rates of CK17 in LSIL and HSIL were 30.00%,63.33%,x²=6.696,P=0.01,respectively,with statistical significance.The positive rate of CK17 was positively correlated with the severity of cervical lesions?r=0.645,P<0.001?.2.The relationship between CK10,CK17 and clinicopathological characteristics of cervical cancer patientsCK10 expression was not related to FIGO stage,lymph node metastasis and pathological type,but was related to the degree of tissue differentiation?x²=5.303,P=0.021?.CK17 expression was not correlated with FIGO stage,lymph node metastasis,pathological type and tissue differentiation,all P>0.05.3.Prognostic aspectsKaplan-Meier survival analysis showed that the 1-year,3-year and 5-year survival rates of 120 patients with early cervical cancer treated by surgery were100%,96.70%and 93.30%,respectively;the 5-year survival rates of CK10 negative group and positive group were 91.50%and 100%,respectively,P>0.05;the 5-year survival rates of CK17 negative group and positive group were 100%and 91.70%,respectively,P>0.05,with no significant difference.Univariate analysis showed that the expression of CK10 and CK17 was not related to prognosis,all P>0.05.According to the expression of CK17 and CK10,patients were divided into four groups.The 1-year,3-year and 5-year survival rates of CK17 positive CK10 negative group were 100%,94.90%and 89.70%,respectively.The 5-year survival rates of CK17 positive and CK10 positive group?CK17 negative and CK10 positive group?CK17 negative and CK10 negative group were 100%,100%and 100%?x²=4.518,P=0.211?,respectively,with no significant difference.The 5-year survival rates of CK10 negative group and positive group were91.50%and 100%respectively,P>0.05.The 5-year survival rates of CK17 negative group and positive group were 100%and 91.70%respectively,P>0.05.Statistical analysis indicated that the difference was not statistically significant.Due to the significant difference in percentage,Cox regression analysis model was established:It indicates that CK10 and CK17 can affect the survival status of patients at least one of them?x²=6.832,P=0.033?,and the risk of death of CK10 negative patients is significantly higher than that of CK10 positive patients over time,and the risk of death of CK17 positive patients is significantly higher than that of CK17 negative patients,but CK10 and CK17 are not independent risk factors affecting the prognosis of patients with early cervical cancer.conclusion1.CK10 is highly expressed in normal cervical tissue,and its expression rate tends to decrease with the increase of cervical lesion severity.The lack of CK10expression may be a sign of malignant transformation of epidermal cells.CK10 was positively correlated with the differentiation of cervical cancer tissues.2.CK17 were not expressed in normal cervical tissue,the expression rate of increase of cervical lesion severity is on the rise,CK17 is likely to become a forecast development trend of cervical lesions or cervical lesion to malignant transformation of specific markers,namely CK17 positive cervical lesions are likely to further development in the future,instead of CK17 negative cervical lesions there is little possibility of further development in the future.3.CK10 and CK17 are not independent risk factors affecting the prognosis of patients with early cervical cancer.The risk of death of patients with CK10 negative is higher than that of patients with CK10 positive,and the risk of death of patients with CK17 positive is higher than that of patients with CK17 negative.