Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages.

Abstract

Although a reduced expression of nm23 has been shown to correlate with a high metastatic potential in some human cancers, in colorectal cancers, conflicting data have been reported. As there are two homologous genes, nm23-H1 and nm23-H2, which encode the A and B subunits of nucleoside diphosphate kinase, efficient and simplified techniques were designed to selectively study nm23-H1 and -H2 expression in 35 colorectal cancers at both the protein and mRNA levels by immunoblotting, immunohistochemistry, and reverse transcription polymerase chain reaction (RT PCR) using specific antibodies and primers. Nm23-H1 and Nm23-H2 proteins were overexpressed in tumours compared with adjacent mucosa. This overexpression was lost, however, in some advanced cases: 89% and 81% of TNM (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression, respectively, which significantly differed from 47% and 38% of stage III-IV tumours. Similar results were seen with nm23-H1 mRNA. Heterogenous labelling of tumoral cells was seen by immunohistological staining. This suggests a dichotomy: an overexpression of nm23-H1 and -H2 linked to early stages of cancer and a loss of nm23-H1 overexpression seen in more advanced stages. Therefore specific nm23-H1 determination should be evaluated as a prognostic factor in human colorectal carcinoma.