RELATIONSHIP BETWEEN THE EXPRESSIONS OF LMP1 AND ECADHERIN/β-CATENIN IN NASOPHARYNGEAL CARCINOMA

Objective: To compare the expression of Epstein-Barr virus encoded LMP1 and E-cadherin/β-catenin in primary and metastatic nasopharyngeal carcinoma (NPC) for the purpose of understanding their relationship. Methods: Twenty-two pairs of biopsies taken from the nasopharynx and cervical lymph node(s) of the same patient with nasopharyngeal carcinoma were collected. The expression of LMP1, E-cadherin and β-catenin was observed on immunostained slides using LSAB method. Results: The expression rate of LMP1 in the 22 metastatic tumors (86.36%, 19/22) was significantly higher than that in the 22 primary growths (68.18%, 15/22), P<0.05. The mean expression percentages of E-cadherin and β-catenin in metastatic tumors (50.11%±22.53% and 66.36±21.05%, respectively) were significantly lower than those in primary growths (71.52±24.34 % and 79.40%±15.05%, respectively), P<0.05. There was a positive correlation between the expressions of E-cadherin and β-catenin either in primary growths or metastatic tumors. Conclusion: The LMP1 is more likely to be expressed in metastatic neoplastic cells of NPC than in primary carcinoma cells, and on the contrary the expression of E-cadherin/β-catenin in metastatic cells was decreased. Accordingly, the LMP1 might have the ability to downregulate the expression of E-cadherin/β-catenin, resulting in enhancement of the invasive capacity of metastatic NPC cells.

ANALYSIS OF 26,826 PATIENTS WITH TUMORS IN THE HEAD AND NECK

A series of 26,826 patients with head and neck tumer as confirmed by pathology from January 1970 to December 1989 are analyzed. It accounted for 39. 5% of all the tumors blopsied in the same interval. In this series, 72. 4% was malignant which accounted for 45. 77% of malignant tumors in different parts of the whole body. For benign tumors in the head and neck, the ratio of male to female was 0. 84:1, and for malignant tumors In the head and neck it was 2. 4:1. The most frequently involved site by the malignant tumors were :nasopharynx, mouth, maxillofacial regions, and neck. THe majority (62. 65%) of malignant tumors were located in the nasopharynx which accounted for 28. 68% of all malignanties of which the ratio of mate and female was 3:1, peak age was 41-50 years, 18 of themwas under 10 years of age, the youngest was 1 1/2 years andthe oldest was 84 years old. These data showed that malignant tunors in the head and neck regions, expecially those in the nasopharynx, are common in Guanxi province, China. The program for cancer research on prevention and treatment should be enforced.

Association of E-cadherin and β-catenin with metastasis in nasopharyngeal carcinoma

Background This study was designed to detect methylation of E-cadherin gene promoter and gene mutation of β-catenin in exon 3 and their expression of protein and mRNA in primary tumor and lymph node metastatic tumor of nasopharyngeal carcinoma (NPC), and investigate the mechanism of invasion and metastasis of neoplastic cells in NPC Methods Fourty-two fresh biopsy samples were taken from untreated NPC patients at the Affiliated Hospital of Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou, China during the period of 1999-2002 Among them 21 were taken from primary tumors and the other 21 from lymph node metastatic tumors The gene promoter methylation of E-cadherin was detected by methylation-specific PCR (MSP) The mutation in exon 3 of β-catenin was detected by direct sequencing analysis RT-PCR, Western blot and immunohistochemical staining were used to detect the mRNA and protein expression patterns in both primary and metastatic tumors of NPC Results Down-regulated expression of E-cadherin in metastatic tumor was compared with that in primary tumor Reduced expression of E-cadherin was found to be correlated with lymph node metastatic tumor of NPC ( P =0 004); but there was no obvious correlation between primary and metastatic tumors in the expression of β-catenin ( P =0 698) The mRNA expression level of E-cadherin in metastatic tumors decreased significantly compared with that in primary tumors However, little change was observed in the mRNA level of β-catenin in different tumor tissues Only 4 samples (19 1%) displayed gene promoter methylation of E-cadherin in primary tumor and 10 samples (47 6%) showed methylated form of E-cadherin The gene promoter methylation of E-cadherin was more common in metastatic tumor than in primary tumor of NPC ( P =0 024) Only 2 (4 76%) of the 42 samples showed mutations in exon 3 of β-catenin at 41 (T41A, ACCGCC) and codon 47 (S47T, AGTACT) The cytoplasmic and nuclear expression of β-catenin in tumor was not found in any samples of NPC Conclusions The results suggest that the downregulation of E-cadherin results from the gene promoter aberrant methylation of E-cadherin and that the methylation of E-cadherin plays an important role in invasion and metastasis of tumor cells in NPC However, β-catenin mutation is an infrequent event in NPC, and β-catenin is not a critical factor influencing the invasion and metastasis of tumor cells in NPC

cDNA representational difference analysis of differentially expressed cDNA sequences in human nasopharyngeal carcinoma

Objective To search differentially expressed sequences correlated with pathogenesis of human nasopharyngeal carcinoma (NPC), including the candidates of tumor suppressor genes Methods Representational difference analysis (RDA) was performed to isolate differentially expressed sequences between cDNA from normal human primary cultures of nasopharyngeal epithelial cells and cDNA from NPC cell line HNE1 The source of differentially expressed products were proved by Southern blot, Northern blot and in situ hybridization The fragments were cloned with pGEM T easy kit and sequenced by the chain termination reaction Results Four differentially expressed cDNA fragments were isolated in the fourth subtractive hybridization using cDNA from normal human nasopharyngeal epithelial cells as tester amplicon and cDNA from NPC cell line HNE1 as driver amplicon by cDNA RDA These differential cDNA fragments revealed that they really came from the tester amplicon and were not expressed or down regulated in the NPC HNE1 cells Some of the genes were expressed only in human nasopharyngeal epithelial cells but deleted or down regulated in the biopsies of NPC Of these obtained clones, some were the sequences of the human known genes including house keeping genes, the others represented novel gene sequences Conclusion The differentially expressed products including the candidates of tumor suppressor genes may be associated with the initiation of the NPC