Studies Of E-cadherin/β-catenin And KAI1/CD82 In Neuroblastoma

Neuroblastoma is a primitive neoplasm of neuroectodermal origin which is the second most common extracranial malignant solid tumors in childhood. The rate of complete resection by operation is lower than other tumors because of the higher malignancy and the aggressive characters. So the main reason of death is the recurrence , infiltration and metastasis in neuroblastoma. The infiltration and metastasis of tumor is a complificated and continuous process, while the tumor cells detached primarily site is a key step and prerequisite. Recently studies indicated that E-cadherin,β-catenin and KAI1/CD82 have played extremely crucial role in various factors interrelated with infiltration and metastasis of tumor cells. The mutation and inactivation of them are an important moleculer event in tumorigenesis and development of tumor.Purposes : ( 1 ) To study clinical pathological characters and immunohistotypes; (2) To study the expression of E-cadherin,β-catenin and KAI1/CD82 in vary differentiated neuroblastoma and observe the relationship between the expression of immunohistochemistry and the characters of clinical pathology; (3) To investigate the molecular biological mechanisms of their abnormal expression.Methods: Ninty cases of neuroblastoma were collected from Xin-hua Hospital and Shanghai Children' s Medical Centers and reviewed all clinical date. Pathological classification was referred based on Shimadestandard. Excepting routine immunostaining with antibodies , such as Vim, NSE, CHG-A, Syn, CD99, N-myc, PGP9.5, CD56, NF, S100, LCA, CK, We also detected the expression of E-cadherin, 3 -catenin and KAI1/CD82 on the collected cases. At same time, we detected the methylation of part region of CpG island on E-cadherin gene and the mutation of exon 3 of P -catenin gene on 7 cases of fresh specimens and 24 cases of paraffin-embedded samples by MSP and PCR, combining with follow-up information , undertaking the correlation and survival date were analysed with SPSS software .Results: (1) Neuroblastoma generally express NSE, CHG-A, Syn, CD56, and the expression of NF, S100, PGP9. 5 is concerned with the differentiated level of neuroblastoma, which the positive expression is commonly in higher differentiated tumor and vice versa. Some cases present Vim expression and the positive rate of N-myc is nearly one-fifth. Otherwise, there is non-specific expression of CD99 in rare case and negative expression of LCA and CK. (2) The positive rate of P -catenin in FH is predominate higher than in UFH, and the abnormal expression of E-cadherin, P -catenin is widespread in neuroblastoma . Furthermore, the positive rate of KAI1/CD82 in neuroblastoma is rather lower and the significant positive correlation with the differentiation. (3) We have detected the region of CpG island promotor from 8705 to 8727 site of E-cadherin was unmethylated in all thirty-one cases and found the mutation or/and rearrangement of P -catenin gene in three-seventh; in two cases, the point mutation is at same site. (4) The survival rate of neuroblastoma in UFH is significant lower than in FH, and the survival time in stage I, II is longer than stage III, IV patients predominately.Conclusions : (T) Neuroblastoma generally expression neuro and neuroendocrine markers, their expression level is correlated with the differentiation of tumors. The application of multiple monoclonal antibodies is very important in diagnosis and differential diagnosis.