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Objective To explore the relationship between the loss of the heterozygosity of nm23-H_1 and the lymph node metastasis in no-small-cell lung cancer (NSCLC). Methods The loss of the heterozygosity of nm23-H_1 gene of cancer tissue and peri-cancerous tissue was detected in 39 patients with NSCLC by Southern blotting. Results The heterozygosity gene of nm23-H_1 is 7.6 kb and 2.3 kb. The LOH rate of the patients with lymph node metastasis (48%, 12/25) was higher than those without lymph node involvement (8%, 1/11) (P
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0.05).Conclusion The increase in the amount of nm23H1 protein expression can play an important role in restraining metastasis of squamous cell lung carcinoma.The heredity instability(MSI and LOH) of nm23H1 gene may not be implicated in expression of the gene and pathogenesis and progression of squamous cell lung carcinoma.
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Objective To explore the prognostic index for nasopharyngeal carcinoma (NPC). Methods The expression of nm23-H 1 protein in the tissue specimens of 115 NPC patients was detected by immunohistochemical S-P staining before radiotherapy. The 115 patients were treated in 1992～1994, underwent the whole radiotherapy, and were followed up for over 5 years. The association of nm23-H 1 protein expression with the clincal staging of NPC, radiosensitivity of tumor, survival rate of patients, and relapse and metastasis of carcinoma was analyzed. Results The positive rate of nm23-H 1 expression in NPC was 47.8%. The tumor clinical staging, lymph nodes metastasis, and patient survival rate were closely correlated with the low level expression of nm23-H 1 protein in NPC. Conclusion The low level expression of nm23-H 1 protein may be associated with the development and poor prognosis of NPC.
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Purpose:To study the expression of CD 44 V 5 and Nm23 H 1 gene products and their significance in esophageal cancer patients.Methods:The expression of CD 44 V 5 and Nm23 H 1 in 85 cases of formalin fixed, paraffin embedded specimens of esophageal cancer were measured by immunohistochemistry S P method. Fifty cases were followed up for 3 years after operation.Results:①The positive expression rate of CD 44 V 5 and Nm23 H 1 was 61.2% 、57 6%, respectively in esophageal cancer.②Overexpression of CD 44 V 5 gene products were closely related with the invasive extent , histopathologic classification , TNM stage ,lymph node metastasis(LNM) and prognosis of Ec( P
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砄bjective:To investigate the variation of nm23 H1 gene structure and its expression in oral squamous cell carcinoma (OSCC) and to study the relationship between nm23 H1 expression and OSCC metastasis to neck lymph nodes.Methods: nm23 H1 gene in the samples of 30 cases of OSCC,7 of normal oral mucous tissue,human OSCC cell line TSCCa and human oral metastatic cancer cell line GNM was extracted and amplified by PCR. PCR products were investegated with SSCP analysis; nm23 m RNA level in the samples was studied by in situ hybridization.The relationship between mRNA expression and metastasis to neck lymph nodes was analyzed statistically.Results: All samples showed no change in nm23 H1 gene structure except deletion in one case of OSCC;7 out of 9 cases with metastasis to neck lymph nodes showed no hybridization signal of nm23 H1 mRNA,however,only 5 were found no nm23 H1 mRNA in 21 cases without metastasis,positive rate of nm23 H1 expression in GNM cells was lower than that in TSCCa (41.2% versus 63.1%);The expression of nm23 H1 gene showed significant negative relationship with neck lymph nodes metastasis ( P
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Objective To study the relationship between the expression of nm23- H1 gene product and early distant metastases in nasopharyngeal carcinoma (NPC). Methods The S- P immunohistochemical method was used to detect the expression of nm23- H1 in 95 cases of NPC. Results The positive rate of nm23- H1 was 47.4 % (45/95). The positive rate of nm23- H1 in early distant metastases group (26.7 %) was much lower than those without distant metastases group (60.0 %) (P
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The nm23 gene was originally identified by differential screening of a cDNA library with RNA from low and high metastatic clones of a murine melanoma cell line. And the nm23 gene has been represented as a metastasis suppressor gene. The product of nm23 gene is known to be identical to nucleoside diphosphate(NDP) kinase. The lack of expression of nm23 protein has been correlated with a poorer prognosis in some human tumors, among which are breast carcinoma, malignant melanoma, gastric carcinoma and hepatcelluar cacin-oma. However, in several types of malignant tumors such as colon carcinoma, neuroblastoma and pancreatic carcinoma, unexpected overexpression of nm23 protein was found as compared with normal tissues. Also in a few studies with cervical carcinoma, the expression of nm23 protein was found to be increased as compared with normal cervical tissue recently. Therefore, in this study, we analyzed the expression of nm23-H1 protein by immunohistochemistry method in a series of 40 cervical carcinomas, to determine whether the alterations in the expression of nm23-H1 protein occured in cervical carcinoma as compared with cervical intraepithelial neoplasia(CIN) and normal cervices, and also analyzed the possible association between nm23 protein expression and prognostic parameters of cervical carcinoma at Ewha Womans University Mokdong Hospital from September 1993 to March 1997. The results obtained were as follows; 1. The mean ages of normal control patients, CIN and cervical carcinomas were 42.9 (+/-5.1) years, 39.5(+/-7.7) years, and 49.3(+/-11.7) years respectively. All cases of cervical carcinoma were squamous cell carcinomas. And the number of each stages Ia, Ib, IIa, IIb, III and IV were 13 cases, 8 cases, 6 cases, 9 cases, 2 cases, and 2 cases respectively. 2. In cervical carcinoma, nm23-H1 protein expression was significantly increased as compared with CIN and normal cervical tissue(t=5.017>1.96). 3. In cervical carcinoma, the nm23-H1 protein expression was more increased in higher stages(p=0.021). But it had no significant correlations with primary tumor size, lymphovascular space invasion, parametrial invasion or lymph node metastasis. Our results on nm23-H1 protein expression in cervical carcinoma suggest that cervical carcinoma seems to belong to the group of tumors, like colon carcinoma and neuroblastoma, pancreatic carcinoma in which nm23-H1 overexpression is associated with a more malignant phenotype. In this study, nm23-H1 protein was more expressed in higher clinical stages of cervical carcinoma. Therefore the expression of nm23-H1 protein probably may have a prognostic significance in cervical carcinoma. But a further prospective study on a larger population is needed to establish the role of nm23 gene in this kind of tumor.
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Female , Humans , Breast Neoplasms , Carcinoma, Squamous Cell , Cell Line , Cervix Uteri , Clone Cells , Colon , Gene Library , Genes, Tumor Suppressor , Immunohistochemistry , Lymph Nodes , Mass Screening , Melanoma , Neoplasm Metastasis , Neuroblastoma , Phenotype , Phosphotransferases , Prognosis , RNAABSTRACT
BACKGROUND AND PURPOSE: We had previously demonstrated by immunohistochemical study (IHS) that nm23-H1 gene may play an important role in disease prognosis as well as its participation in metastasis of urothelial cancer. The purpose of present study was 1) to reexamine the role of nm23-H1 gene in urothelial cancers at molecular level, 2) to identify the molecular mechanism of decreased immunoreactivity for nm23-H1 protein in metastatic urothelial cancers, and 3) to identify whether IHS is reliable in studying the expression of nm23-H1. MATERIALS AND METHODS: We studied expression level and mutation profiles of nm23-H1 gene in 25 fresh surgical specimens of urothelial cancer by reverse transcription polymerase chain reaction(RT-PCR)-Southern blotting analysis, and PCR of genomic DNA followed by single strand conformation polymorphism and sequencing analysis. The results of RT-PCR-Southern blotting were comparatively analyzed with those of IHS. RESULTS: mRNA transcript levels of nm23-H1 gene were significantly decreased in tumor tissues with metastasis as compared with those without metastasis. The transcript levels of nm23-H1 gene were also significantly decreased in metastatic tumor tissues as compared with primary tumor tissues. Point mutation of nm23-H1 gene was detected in only 1 of 13 urothelial cancer tissues with metastasis, whereas, mutation was observed in none of those without metastasis. The results of IHS corresponded with those of RT-PCR-Southern blotting analysis in 23 of 25 specimens. CONCLUSIONS: The nm23-H1 gene may play an important role in metastasis of urothelial cancer. Decreased transcription at mRNA level may be a major molecular mechanism of loss of immunoreactivity for nm23-H1 protein in urothelial cancer. IHS used in the present study may be a clinically useful method to study the expression of nm23-H1 and to predict metastasis potential and prognosis of urothelial cancers.