Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Dec;70(6):1224–1228. doi: 10.1038/bjc.1994.477

NM23 expression in metastasis of malignant melanoma is a predictive prognostic parameter correlated with survival.

L Xerri 1, J J Grob 1, Z Battyani 1, J Gouvernet 1, J Hassoun 1, J J Bonerandi 1
PMCID: PMC2033668  PMID: 7981081

Abstract

The management of patients presenting with metastatic malignant melanoma (MM) is hampered by the substantial variability in survival of these patients and the lack of prognostic markers. In the search for a reliable predictive parameter, we have investigated the expression of the nm23 gene, considered to be a major regulator of the metastatic process. We have analysed by Northern blot the nm23 mRNA level in tumour tissue obtained from metastases of 20 stage II and ten stage III patients with MM. Normal human tissues and benign naevi were simultaneously examined. The level of nm23 expression was highly heterogeneous in MM metastases, with a mean value which was higher than the mean level in normal tissues and naevi. Correlative study was focused on the overall survival following resection of the metastasis in which nm23 Northern blot analysis was performed. Patients displaying higher nm23 expression in metastatic tissue (above the mean level) tended to have a longer survival than others (P = 0.08), and this difference was significant for patients presenting with isolated regional lymph node involvement (P = 0.035). The time from biopsy of the primary MM to the appearance of the first lymph node metastasis also showed a positive correlation with the nm23 mRNA level in this metastasis. The present study is not only in accordance with previous reports showing that the nm23 gene may be implicated in MM progression, but also suggests the reliable value of nm23 expression as a prognostic marker for patients presenting with metastatic MM.

Full text

PDF
1224

Images in this article

1225Figure 1
on p.1225

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes R., Masood S., Barker E., Rosengard A. M., Coggin D. L., Crowell T., King C. R., Porter-Jordan K., Wargotz E. S., Liotta L. A. Low nm23 protein expression in infiltrating ductal breast carcinomas correlates with reduced patient survival. Am J Pathol. 1991 Aug;139(2):245–250. [PMC free article] [PubMed] [Google Scholar]
  2. Bevilacqua G., Sobel M. E., Liotta L. A., Steeg P. S. Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res. 1989 Sep 15;49(18):5185–5190. [PubMed] [Google Scholar]
  3. Biggs J., Hersperger E., Steeg P. S., Liotta L. A., Shearn A. A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase. Cell. 1990 Nov 30;63(5):933–940. doi: 10.1016/0092-8674(90)90496-2. [DOI] [PubMed] [Google Scholar]
  4. Bosma P. J., Kooistra T. Different induction of two plasminogen activator inhibitor 1 mRNA species by phorbol ester in human hepatoma cells. J Biol Chem. 1991 Sep 25;266(27):17845–17849. [PubMed] [Google Scholar]
  5. Cohn K. H., Wang F. S., Desoto-LaPaix F., Solomon W. B., Patterson L. G., Arnold M. R., Weimar J., Feldman J. G., Levy A. T., Leone A. Association of nm23-H1 allelic deletions with distant metastases in colorectal carcinoma. Lancet. 1991 Sep 21;338(8769):722–724. doi: 10.1016/0140-6736(91)91444-y. [DOI] [PubMed] [Google Scholar]
  6. Flørenes V. A., Aamdal S., Myklebost O., Maelandsmo G. M., Bruland O. S., Fodstad O. Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res. 1992 Nov 1;52(21):6088–6091. [PubMed] [Google Scholar]
  7. Gilles A. M., Presecan E., Vonica A., Lascu I. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem. 1991 May 15;266(14):8784–8789. [PubMed] [Google Scholar]
  8. Hailat N., Keim D. R., Melhem R. F., Zhu X. X., Eckerskorn C., Brodeur G. M., Reynolds C. P., Seeger R. C., Lottspeich F., Strahler J. R. High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest. 1991 Jul;88(1):341–345. doi: 10.1172/JCI115299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Haut M., Steeg P. S., Willson J. K., Markowitz S. D. Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential. J Natl Cancer Inst. 1991 May 15;83(10):712–716. doi: 10.1093/jnci/83.10.712. [DOI] [PubMed] [Google Scholar]
  10. Henderson B. R. Expression of the nm23-2/NDP kinase alpha gene in rat mammary and oral carcinoma cells of varying metastatic potential. Br J Cancer. 1993 Nov;68(5):874–878. doi: 10.1038/bjc.1993.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hennessy C., Henry J. A., May F. E., Westley B. R., Angus B., Lennard T. W. Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis. J Natl Cancer Inst. 1991 Feb 20;83(4):281–285. doi: 10.1093/jnci/83.4.281. [DOI] [PubMed] [Google Scholar]
  12. Leone A., McBride O. W., Weston A., Wang M. G., Anglard P., Cropp C. S., Goepel J. R., Lidereau R., Callahan R., Linehan W. M. Somatic allelic deletion of nm23 in human cancer. Cancer Res. 1991 May 1;51(9):2490–2493. [PubMed] [Google Scholar]
  13. Rosengard A. M., Krutzsch H. C., Shearn A., Biggs J. R., Barker E., Margulies I. M., King C. R., Liotta L. A., Steeg P. S. Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development. Nature. 1989 Nov 9;342(6246):177–180. doi: 10.1038/342177a0. [DOI] [PubMed] [Google Scholar]
  14. Sirott M. N., Bajorin D. F., Wong G. Y., Tao Y., Chapman P. B., Templeton M. A., Houghton A. N. Prognostic factors in patients with metastatic malignant melanoma. A multivariate analysis. Cancer. 1993 Nov 15;72(10):3091–3098. doi: 10.1002/1097-0142(19931115)72:10<3091::aid-cncr2820721034>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  15. Stahl J. A., Leone A., Rosengard A. M., Porter L., King C. R., Steeg P. S. Identification of a second human nm23 gene, nm23-H2. Cancer Res. 1991 Jan 1;51(1):445–449. [PubMed] [Google Scholar]
  16. Steeg P. S., Bevilacqua G., Kopper L., Thorgeirsson U. P., Talmadge J. E., Liotta L. A., Sobel M. E. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988 Apr 6;80(3):200–204. doi: 10.1093/jnci/80.3.200. [DOI] [PubMed] [Google Scholar]
  17. Stryer L., Bourne H. R. G proteins: a family of signal transducers. Annu Rev Cell Biol. 1986;2:391–419. doi: 10.1146/annurev.cb.02.110186.002135. [DOI] [PubMed] [Google Scholar]
  18. Yamaguchi A., Urano T., Fushida S., Furukawa K., Nishimura G., Yonemura Y., Miyazaki I., Nakagawara G., Shiku H. Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis. Br J Cancer. 1993 Nov;68(5):1020–1024. doi: 10.1038/bjc.1993.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zentella A., Weis F. M., Ralph D. A., Laiho M., Massagué J. Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function. Mol Cell Biol. 1991 Oct;11(10):4952–4958. doi: 10.1128/mcb.11.10.4952. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES