The Mobile Expression Of JNK2 And SHH Protein In The Process From Precancerous Lesions To Early Carcinoma Of The Esophagus

Background and Objective Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common malignant tumors of a digestive tract. The incidence and mortality rates of this kind of tumor is the 8th and 6th worldwide respectively. It is believed that detection, diagnosis and treatment in its early stages are the key points in decreasing the mortality of the patients of esophageal cancer. Therefore, the research of the mechanism in the development from precancerous lesions of the esophagus to early carcinoma and the biomarkers for early screening and diagnosis, has become one of the hot points in the research field of EC. It is important to recognize the occurrence and development of EC.JNK2 is one member of the family of c-Jun N-terminal kinase (JNK) singal pathway. It is ubiquitously expressed in human body. It has some effects on the homeostasis of cells and the growth of tumor cells. SHH is one member of the family of Hedgehog singal pathway. It is applied mostly with the development process by Hedgehog singal pathway. It is located on 7q36, encoding one secretary protein. It is one of the signal transduced elements which is related to the growth and development closely. It is mainly expressed in the entodermal epithelium, and it has an important effect on embryonic development, histodifferentiation, tumorigenesis and the development of tumors. This study was designed to investigate the expressions of JNK2 and SHH in esophageal carcinogenesis in the same individual on protein level and their mobile changes and their correlation in different stages, which may be expected to offer the biomarkers for early diagnosis of esophageal cancer.Material and MethodsMaterials: Two parts of specimens are included in the study:(1) The samples partly were obtained from 10 cases with esophageal normal tissues, 20 cases with precancerous lesions and 19 cases with early carcinoma of the esophagus.(2) The other part of the materials were twice biopsy samples of the esophageal squamous cancer in the same individual from Anyang Tumor Hospital which were collected from a high-risk area before and after two years. In these samples, 17 cases with esophageal epithelial dysplasia which developed to carcinoma in situ two years later were chosen as carcinogenesis group. 40 cases with dysplasia detected in the same high-risk population who have not developed to cancer after 2-year-follow-up were chosen as non-carcinogenesis group. In addition,20 cases of biopsy samples from symptom-free subjects in the same area were selected as the healthy control group.Methods: (1) Immunohistochemistry (S-P method) was used to detect the expression of JNK2 and SHH in each group of the two-part specimens and analyze the mobile changes of JNK2 and SHH in the carcinogenesis group and the non- carcinogenesis group.(2 ) Chi-squared test (Fisher'exact test of probabilities) was performed with SPSS (10.0 version) to evaluate all the experimental data. Correlation analysis of contingency table was used between the expression of the biomarkers.α=0.05 was chosen as the standard for tests.Results: (1) the expression of JNK2 protein:ⅠThe positive rates of JNK2 expression in esophageal normal tissues ,precancerous lesions and early carcinoma of the esophagus were 20%(2/10),25%(5/20),63.16%(12/19) respectively .The expression of JNK2 protein in early carcinoma was significantly higher than that in precancerous lesions and esophageal normal tissues(P <0.05).But there was no significant difference between the precancerous lesions and esophageal normal tissues (P >0.05) .Ⅱ①According to the expressive degrees of JNK2, the positive rates of JNK2 expression in carcinogenesis group,non-carcinogenesis group and healthy control group during the first biopsy were 23.53%,25.00%,20. 00% respectively. There was no significant difference among the three groups(P >0.05 ). But two years later, the positive expression rate in carcinogenesis group was 64.71% and significantly higher than that in non-carcinogenesis group and healthy control group (P <0.05 ). There was no significant difference between the later two groups (P >0.05) .②The positive rate of carcinogenesis group in 2000 was significantly increased compared with that in 1998 (P <0.05) .However, the rate was lower in non-carcinogenesis group in 2000 than that in 1998(P >0.05).③Mobile changes of JNK2 between the two groups before and after two years showed a significant difference (P < 0.05) .The instances of JNK2 expression changing from negative to positive were higher in carcinogenesis group than in non-carcinogenesis group (P <0.05 ) ,but the instances changing from positive to negative were lower in carcinogenesis group than in non-carcinogenesis group (P >0.05) .(2) the expressions of SHH protein:ⅠThe expression rates of SHH in esophageal normal tissues ,precancerous lesions and early carcinoma of the esophagus were 30%(3/10),45%(9/20),73.68%(14/19) respectively. The expression of SHH protein in early carcinoma was significantly higher than that in precancerous lesions and esophageal normal tissues(P<0.05).But there was no significant difference between the rates of precancerous lesions and esophageal normal tissues (P>0.05) .Ⅱ①According to the expressive degrees of SHH, The expression rates of SHH in carcinogenesis group,non-carcinogenesis group and healthy control group during the first biopsy were 29.41%,15. 00%,25. 00% respectively. There was no difference among the three groups (P>0.05). But two years later, the positive expression rate in carcinogenesis group was 70.59% and significantly higher than that in non- carcinogenesis group and healthy control group (P <0.05) .There was no significant difference between the later two groups (P > 0.05) .②The positive rate in carcinogenesis group in 2000 was significantly increased compared with that in 1998 (P <0.05) .However, the rate was lower in non-carcinogenesis group in 2000 than that in 1998 (P >0.05) .③Mobile changes of SHH between the two groups in before and after two years showed a significant difference (P <0.05) .The instances of SHH expression changing from negative to positive were higher in carcinogenesis group than in non-carcinogenesis group(P <0.05),but the instances changing from positive to negative were lower in carcinogenesis group than in non-carcinogenesis group (P >0.05) .Conclusions :1. Compared with that in normal esophageal tissue,the expression of JNK2 and SHHin esophageal dysplasia and early esophageal carcinoma are higher. Followed with the transformation of dysplasia into early carcinoma, the expression rate of JNK2 increases significantly. It indicates that the overexpression of JNK2 and SHH may be the early molecular events in the carcinogenesis of esophageal carcinoma.2. The analysis result of mobile changes suggestes that the activatation of JNK2 andSHH may play an important role in esophageal carcinogenesis and the process of cancerization.3. Analyzing the expression of JNK2 and SHH in each group of the two part experiment by contingency table ,the results show no significant correlation the expression of JNK2 and SHH. But it shows the consistence in the expression of JNK2 and SHH ,based on the mobile changes of JNK2 and SHH observed. This suggests that there may be certain correlation between JNK2 and SHH, but it is required to study further through increasing sample amount and get the verification of cytobiology study.