nm23H1 expression and its role in the evolution of non-gastrointestinal malignancies

Abstract

The role of nm23H1 genetic instability is not limited to gastrointestinal malignancies. A similar close relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies. For instance, in oral malignant melanomas with lymphoid metastasis, the nm23H1 expression is significantly lower in contrast to tumors with no lymphoid metastasis. Similarly, increased metastasis is seen in non small cell lung cancers following down regulation of nm23H1 in conjunction with KAI-1 down regulation. There is an inverse relationship between tumor stage and metastasis and nm23H1 expression in individuals with prostate carcinomas and a similar relationship exists between microsatellite instability of the nm23H1 gene and ovarian carcinogenesis. For instance, nearly 70.5% of stageI-II ovarian tumors express nm23H1 in sharp contrast to only 25% of stage III-IV ovarian tumors. As is clearly evident, nm23H1 has a major role in gastrointestinal and non-gastrointestinal carcinogenesis. The coming few years will hopefully see the development of new strategies by virtue of which we can alter nm23H1 expression and thus decrease the risk of metastasis in malignant tumors.

Key Words: nm23H1, Non small cell lung cancers, Prostate carcinomas, Nasopharyngeal carcinomas

TO THE EDITOR

The recent article by Yang et al[1] about the relationship between gastrointestinal malignancies and nm23H1 genetic instability is highly interesting. Interestingly, the role of nm23H1 genetic instability is not limited to gastrointestinal malignancies. In fact, a similar close and intricate relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies.

For instance, Korabiowska et al[2] have shown that the nm23H1 expression is significantly lower in oral malignant melanomas with lymphoid metastasis than in tumors with no lymphoid metastasis. Similarly, increased metastasis is seen in non small cell lung cancers following down regulation of nm23H1 in conjunction with KAI-1 down regulation[3]. Similarly, there is an inverse relationship between tumor stage and metastasis and nm23H1 expression in individuals with prostate carcinomas[4]. A similar relationship exists between microsatellite instability of the nm23H1 gene and ovarian carcinogenesis. For instance, nearly 70.5% of stageI-II ovarian tumors express nm23H1 in sharp contrast to only 25% of stage III-IV ovarian tumors[5].

Similarly, nm23H1 expression may be used to determine response to treatment. For instance, following radiotherapy, the five-year survival rate in patients with nasopharyngeal carcinomas and high expression of nm23H1 is 53.2% in comparison to only 22.7% in individuals with low expression of nm23H1[6]. In fact, transfer of nm23H1 via adeno viruses is rapidly emerging as a potential therapeutic tool to prevent metastasis. For instance, this method has been shown to decrease metastasis in implantation models of ovarian cancer [7].

As is clearly evident, nm23H1 plays a major role in gastrointestinal and non-gastrointestinal carcinogenesis. The coming few years will hopefully see the development of new strategies by virtue of which we can alter nm23H1 expression and thus decrease the risk of metastasis in malignant tumors.