Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1998 Apr;77(7):1164–1168. doi: 10.1038/bjc.1998.193

NM23-H1 immunostaining is inversely associated with tumour staging but not overall survival or disease recurrence in colorectal carcinomas.

P Y Cheah 1, X Cao 1, K W Eu 1, F Seow-Choen 1
PMCID: PMC2150137  PMID: 9569056

Abstract

The NM23-H1 gene product has been recently identified as a potential metastasis suppressor. Studies on breast carcinomas have shown an inverse correlation between NM23-H1 status and stage of carcinogenesis and overall survival. However, in colorectal cancer, conflicting data have been reported. This study aimed to investigate whether NM23-H1 immunostaining is correlated with tumour stage, overall survival, disease recurrence, tumour differentiation, age and sex in colorectal carcinomas for the Singapore population using chi-square analysis. The staining was performed on 141 paraffin-embedded surgical specimens collected between 1991 and 1992 using a monoclonal anti-NM23-H1 antibody. Follow-up of patients was until time of death or for 5 years. There was a very significant inverse association between tumour staging and NM23-H1 status (P = 0.0004). However, NM23-H1 expression was not significantly correlated to overall 5-year survival, disease recurrence, tumour differentiation, age or sex. Thus, although NM23-H1 may be involved in suppressing metastasis, NM23-H1 immunohistochemistry has no prognostic value in colorectal cancer. This is the first report of a significant inverse association of NM23-H1 status with tumour staging in colorectal cancer which showed no correlation with overall survival or disease recurrence. Our result thus cautions against the practice of equating an inverse relation of genetic markers with tumour staging to survival or disease recurrence.

Full text

PDF
1168

Images in this article

1165Figure 1
on p.1165

Selected References

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

  1. Cawkwell L., Lewis F. A., Quirke P. Frequency of allele loss of DCC, p53, RBI, WT1, NF1, NM23 and APC/MCC in colorectal cancer assayed by fluorescent multiplex polymerase chain reaction. Br J Cancer. 1994 Nov;70(5):813–818. doi: 10.1038/bjc.1994.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cohn K. H., Ornstein D. L., Wang F., LaPaix F. D., Phipps K., Edelsberg C., Zuna R., Mott L. A., Dunn J. L. The significance of allelic deletions and aneuploidy in colorectal carcinoma. Results of a 5-year follow-up study. Cancer. 1997 Jan 15;79(2):233–244. [PubMed] [Google Scholar]
  3. 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]
  4. Freije J. M., Blay P., MacDonald N. J., Manrow R. E., Steeg P. S. Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro. J Biol Chem. 1997 Feb 28;272(9):5525–5532. doi: 10.1074/jbc.272.9.5525. [DOI] [PubMed] [Google Scholar]
  5. Indinnimeo M., Giarnieri E., Stazi A., Cicchini C., Brozzetti S., Valli C., Carreca I., Vecchione A. Early stage human colorectal cancer: prognostic value of nm23-H1 protein overexpression. Cancer Lett. 1997 Jan 1;111(1-2):1–5. doi: 10.1016/s0304-3835(96)04472-2. [DOI] [PubMed] [Google Scholar]
  6. Leone A., Flatow U., King C. R., Sandeen M. A., Margulies I. M., Liotta L. A., Steeg P. S. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell. 1991 Apr 5;65(1):25–35. doi: 10.1016/0092-8674(91)90404-m. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Lindmark G. NM-23 H1 immunohistochemistry is not useful as predictor of metastatic potential of colorectal cancer. Br J Cancer. 1996 Nov;74(9):1413–1418. doi: 10.1038/bjc.1996.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. MacDonald N. J., De la Rosa A., Benedict M. A., Freije J. M., Krutsch H., Steeg P. S. A serine phosphorylation of Nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential. J Biol Chem. 1993 Dec 5;268(34):25780–25789. [PubMed] [Google Scholar]
  10. Martinez J. A., Prevot S., Nordlinger B., Nguyen T. M., Lacarriere Y., Munier A., Lascu I., Vaillant J. C., Capeau J., Lacombe M. L. Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages. Gut. 1995 Nov;37(5):712–720. doi: 10.1136/gut.37.5.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Myeroff L. L., Markowitz S. D. Increased nm23-H1 and nm23-H2 messenger RNA expression and absence of mutations in colon carcinomas of low and high metastatic potential. J Natl Cancer Inst. 1993 Jan 20;85(2):147–152. doi: 10.1093/jnci/85.2.147. [DOI] [PubMed] [Google Scholar]
  12. Royds J. A., Cross S. S., Silcocks P. B., Scholefield J. H., Rees R. C., Stephenson T. J. Nm23 'anti-metastatic' gene product expression in colorectal carcinoma. J Pathol. 1994 Mar;172(3):261–266. doi: 10.1002/path.1711720306. [DOI] [PubMed] [Google Scholar]
  13. Ruiz P., Günthert U. The cellular basis of metastasis. World J Urol. 1996;14(3):141–150. doi: 10.1007/BF00186893. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Tannapfel A., Köckerling F., Katalinic A., Wittekind C. Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma. Dis Colon Rectum. 1995 Jun;38(6):651–654. doi: 10.1007/BF02054128. [DOI] [PubMed] [Google Scholar]
  16. Wang L., Patel U., Ghosh L., Chen H. C., Banerjee S. Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res. 1993 Feb 15;53(4):717–720. [PubMed] [Google Scholar]
  17. 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]
  18. Zeng Z. S., Hsu S., Zhang Z. F., Cohen A. M., Enker W. E., Turnbull A. A., Guillem J. G. High level of Nm23-H1 gene expression is associated with local colorectal cancer progression not with metastases. Br J Cancer. 1994 Nov;70(5):1025–1030. doi: 10.1038/bjc.1994.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. de la Rosa A., Williams R. L., Steeg P. S. Nm23/nucleoside diphosphate kinase: toward a structural and biochemical understanding of its biological functions. Bioessays. 1995 Jan;17(1):53–62. doi: 10.1002/bies.950170111. [DOI] [PubMed] [Google Scholar]

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

RESOURCES