engleski

Tumor suppressor gene nm23-H1 in sporadic colon adenocarcinoma

The discovery of genetic alterations in oncogenes and tumor-suppressor genes, which accompany tumor formation in a wide variety of human tumor types, has encouraged the search for genes that may promote or suppress tumor spread and metastasis. Nm23 gene was originally identified by differential hybridisation of K-1735 melanoma cell line clones of varying metastatic potential. A tumor metastases-suppressor function was implicated by the reduced expression of nm23 in highly metastatic sublines compared with non-metastatic sublines derived from the same K-1735 clone. Nm23 expression has been shown to be higher in several different tumors of lower metastatic potential than in the corresponding tumors of higher metastatic potential, including breast, hepatocellular, ovarian and gastric carcinomas and melanoma. In other tumors, such as neuroblastoma, pancreatic carcinoma and head and neck carcinomas, surprisingly, the opposite trend has been reported. The purpose of this study was to evaluate whether the expression of the nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with tumor stage and grade of tumor differentiation. In addition, we also investigated the correlation of nm23-H1 expression with 5-year survival. Paraffin tissue sections were analyzed immunohistochemically using monoclonal antibody NM301 to human nm23-H1 protein. DNAs (normal and tumor) isolated from microdissections of parafin sections were used for LOH analysis. Of 102 adenocarcinomas that were examined, 41% showed a weak positive immunostaining for nm23-H1 protein.The most nm23-H1 positive tumors were in Dukes' B (67%) and in the well differentiated tumors (65%). Statistical analysis showed that there was no statistically significant difference in survival between the patients with nm23-H1 positive tumors and patients with tumors that were not stained for nm23-H1 protein. To analyze LOH at the nm23-H1 gene we used VNTR marker located in untranslated 5' region of the nm23-H1 gene. At this nm23-H1 locus 60% of samples were informative and 33% of them demonstrated LOH. The nm23-H1 LOH was more frequent in tumors that were larger than 5 cm than in smaller ones. Positive correlation was found between the nm23-H1 LOH and histological grade of tumors. Positive correlation was also found between the nm23-H1 LOH and Dukes' stage of tumor samples.

nm23-H1; sporadic colon adenocarcinoma

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