| Background and objectiveEsophageal carcinoma is one of the most common malignant tumors worldwide,and the sixth most common cause of death from cancer.China is one of the countries with high incidence rate and high mortality rate of esophageal carcinoma.Esophageal carcinoma is the second cause of death from malignant tumors in China.The highest incidence rates of esophageal carcinoma in China are found in Taihang Mountain,the border of Fujian and Guangdong(Chaozhou and Shantou area),Xinjiang Kazakhstan,and so on.In histological,esophageal carcinoma is divided into squamous cell carcinoma,adenocarcinoma,small cell carcinoma and adenosquamous carcinoma.Esophageal Squamous Cell Carcinoma(ESCC)is the most common type in China,accounting for about 90%.Despite the progress and development of medicine in recent years,the diagnosis and treatment of esophageal carcinoma have been greatly improved,and the mode of comprehensive treatment of esophageal carcinoma has also been basically formed,the overall treatment effect is not ideal,the total survival rate of 5 years after the operation is only 20%-30%.The symptoms of early esophageal carcinoma are not specific.Upon presentation with dysphagia,over 70% of patients will already have lymph node metastasis.Of those who survive surgery,80% will eventually die from tumor recurrence;at least 40% of these are due to recurrence in lymph nodes.The latest research has shown that even if the primary tumor is removed,lymph node metastases can invade local blood vessels,exit the node,and colonize distant organs in mice.Thus it can be seen that lymph node status is one of the most important prognostic factors for esophageal carcinoma.As a specific marker of squamous epithelium,p40 is often used to identify squamous epithelial lesions or tumors.Although p40 is one of the specific markers of ESCC,the relationship between the expression of p40 and the prognosis is controversial.Cytokeratin(CK)is the characteristic marker of epithelial cells.The keratins CK7,CK8,CK18 and CK19 are often expressed in simple epithelial cells,which usually be used to diagnose the origin of the adenocarcinoma.In most of the adenocarcinoma,the keratins CK7,CK8,CK18 and CK19 often show diffuse expression.However,they are not present diffuse expression in some of the adenocarcinoma.Furthermore,their low expression in adenocarcinoma also indicates that the patient has a bad prognosis.In addition,it has been found that CK7,CK8,CK18 and CK19 can also be expressed in some squamous cell carcinoma cases,and their expression is closely related to the prognosis of the patients.Therefore,it would bring some confusion to pathologists and cause a misdiagnosis of pathological diagnosis.In view of this,the present study observed the expression of CK7,CK8/18,CK19 and p40 in ESCC and lymph node metastases,and analyzed the correlation between the expression of CK7,CK8/18,CK19 and p40 and the clinicopathological parameters,the differences of CK7,CK8/18,CK19 and p40 in the primary tumor and lymph node metastasis and their differences with the prognosis were also analyzed.Methods1.190 cases of ESCC with surgical resection,154 cases of normal esophageal mucosa adjacent to cancer and 64 cases of lymph node metastasis were collected,which were diagnosised by pathologist during 2012 in the First Affiliated Hospital of Zhengzhou University.The expression of CK7,CK8/18,CK19 and p40 in normal esophageal tissue,esophageal squamous cell carcinoma and lymph node metastases was detected by immunohistochemical S-P method,and analyzed the correlation between CK7,CK8/18,CK19 and p40 with sex,age,tumor site,degree of differentiation,depth of invasion,lymph node metastasis,pTNM staging,and other clinicopathological parameters.The differences of CK7,CK8/18,CK19 and p40 in the primary tumor and lymph node metastasis and their differences with the prognosis were also analyzed.2.All patients were followed up by telephone or review.The follow up time was deadline in July 31,2017.There were 108 patients successful follow-up in 190 cases,and the follow-up rate was 56.84%.The total survival time was from the date of operation to the date of death due to the disease or the date of survival at the last follow-up.Results1.In normal esophageal tissue,CK19 was expressed in the full layer of stratified squamous epithelium,and p40 in the basal layer and sub basal layer,while both CK7 and CK8/18 were not expressed in the esophageal mucosa.CK19 and p40 were both observed in 190 cases of ESCC tumor tissues.A strong expression of p40 and CK19 were recognized in 147 cases(77.37%)and 151 cases(79.47%),respectively.At the same time,43 cases(22.63%)and 39 cases(20.53%)presented a diminished expression.The positive rates of CK7 and CK8/18 were 15.26%(29 /190)and 31.05%(59/190),respectively.Besides that,CK19 and p40 were also both observed in 64 cases of lymph node metastasis.A strong expression of CK19 and p40 were recognized in 57 cases(89.06%)and 51 cases(79.69%),respectively.At the same time,7 cases(10.94%)and 13 cases(20.31%)presented a diminished expression.The positive rates of CK7 and CK8/18 were 17.19%(11 /64)and 43.75%(28/64),respectively.The inconsistency rates of CK7,CK8/18,CK19 and p40 in the primary tumor and lymph node metastases were 21.88%(14/64),28.13%(18/64),26.56%(17/64)and 20.31%(13/64)respectively.In most ESCC,the expression of CK7,CK8/18,CK19 and p40 were maintained between the primary sites and corresponding lymph node metastatic deposits,but a portion of CK19 and p40 low expression primary tumors displayed upregulation of CK19 and p40 in lymph node metastatic deposits(P < 0.001,P=0.003).2.The expression of CK7 in ESCC was significantly correlated with the degree of tumor differentiation,lymph node metastasis and pTNM staging(P < 0.05).The expression of CK8/18 in ESCC was significantly correlated with the degree of tumor differentiation and lymph node metastasis(P < 0.05).The expression level of CK19 in ESCC was negatively correlated with lymph node metastasis and pTNM staging(P < 0.05).The expression level of p40 was negatively associated with the degree of differentiation,lymph node metastasis and pTNM stage(P < 0.05).In both early and advanced ESCC,the low expression of p40 indicates that lymph node metastasis is easily happened,while the expression of CK7 and CK8/18 and the low expression of CK19 only in advanced ESCC indicate the patients are more likely to have lymph node metastasis.3.When ESCC is not accompanied by lymph node metastasis,the expression of CK8/18 in the primary tumor is an independent prognostic factor.However when ESCC is accompanied by lymph node metastasis,the expression of CK7 in the primary tumor and the low expression of CK19 in the lymph node metastases can be used as an independent indicator of poor prognosis.Conclusions1.We cannot exclude SCC with the diminished expression of CK19 and p40 and the expression of CK7 and CK8/18 in the low differentiated esophageal carcinomas.2.In both early and advanced ESCC,the low expression of p40 indicates that lymph node metastasis is easily happened,while the expression of CK7 and CK8/18 and the low expression of CK19 only in advanced ESCC indicate the patients are more likely to have lymph node metastasis.3.When the squamous carcinoma of the esophagus is not accompanied by lymph node metastasis,the expression of CK8/18 in the primary tumor is an independent prognostic factor.However,when ESCC is accompanied by lymph node metastasis,the expression of CK7 in the primary tumor and the low expression of CK19 in the lymph node metastases can be used as an independent indicator of poor prognosis. |
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