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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Jul;145(1):26–32.

NM23 protein in neoplastic and nonneoplastic thyroid tissues.

P Bertheau 1, A De La Rosa 1, P S Steeg 1, M J Merino 1
PMCID: PMC1887288  PMID: 8030752

Abstract

The expression of nm23 gene products has been associated with a lower metastatic potential and better outcome in malignant tumors. We have used immunohistochemistry to study the expression of nm23 protein in thyroid tissues from 101 patients consisting of 78 malignant neoplasms, 13 adenomas, and 10 other benign conditions. Cytoplasmic staining for nm23 protein was identified in normal tissues and in most benign and malignant lesions and did not correlate with either histological type of clinical outcome. Nuclear staining was seen in 93% of normal tissues and in 29% of primary carcinomas of the thyroid and was associated with a longer disease-free survival (P = 0.03). Membranous staining was present in some tumors but absent in normal thyroid. In conclusion, nm23 protein has a combined pattern of distribution among subcellular compartments in thyroid tissues. Although there was no significant association between cytoplasmic or membranous expression and histological type of tumor or survival nm23 nuclear expression may be a useful marker in assessing the evolution of thyroid tumors.

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  1. Arai T., Watanabe M., Onodera M., Yamashita T., Masunaga A., Itoyama S., Itoh K., Sugawara I. Reduced nm 23-H1 messenger RNA expression in metastatic lymph nodes from patients with papillary carcinoma of the thyroid. Am J Pathol. 1993 Jun;142(6):1938–1944. [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Dumas C., Lascu I., Moréra S., Glaser P., Fourme R., Wallet V., Lacombe M. L., Véron M., Janin J. X-ray structure of nucleoside diphosphate kinase. EMBO J. 1992 Sep;11(9):3203–3208. doi: 10.1002/j.1460-2075.1992.tb05397.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Hawk W. A., Hazard J. B. The many appearances of papillary carcinoma of the thyroid. Cleve Clin Q. 1976 WINTER;43(4):207–215. doi: 10.3949/ccjm.43.4.207. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Higashiyama M., Doi O., Yokouchi H., Kodama K., Nakamori S., Tateishi R., Kimura N. Immunohistochemical analysis of nm23 gene product/NDP kinase expression in pulmonary adenocarcinoma: lack of prognostic value. Br J Cancer. 1992 Sep;66(3):533–536. doi: 10.1038/bjc.1992.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirayama R., Sawai S., Takagi Y., Mishima Y., Kimura N., Shimada N., Esaki Y., Kurashima C., Utsuyama M., Hirokawa K. Positive relationship between expression of anti-metastatic factor (nm23 gene product or nucleoside diphosphate kinase) and good prognosis in human breast cancer. J Natl Cancer Inst. 1991 Sep 4;83(17):1249–1250. doi: 10.1093/jnci/83.17.1249. [DOI] [PubMed] [Google Scholar]
  11. Johnson T. L., Lloyd R. V., Thompson N. W., Beierwaltes W. H., Sisson J. C. Prognostic implications of the tall cell variant of papillary thyroid carcinoma. Am J Surg Pathol. 1988 Jan;12(1):22–27. doi: 10.1097/00000478-198801000-00003. [DOI] [PubMed] [Google Scholar]
  12. Kantor J. D., McCormick B., Steeg P. S., Zetter B. R. Inhibition of cell motility after nm23 transfection of human and murine tumor cells. Cancer Res. 1993 May 1;53(9):1971–1973. [PubMed] [Google Scholar]
  13. Kobayashi S., Iwase H., Itoh Y., Fukuoka H., Yamashita H., Kuzushima T., Iwata H., Masaoka A., Kimura N. Estrogen receptor, c-erbB-2 and nm23/NDP kinase expression in the intraductal and invasive components of human breast cancers. Jpn J Cancer Res. 1992 Aug;83(8):859–865. doi: 10.1111/j.1349-7006.1992.tb01991.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lacombe M. L., Sastre-Garau X., Lascu I., Vonica A., Wallet V., Thiery J. P., Véron M. Overexpression of nucleoside diphosphate kinase (Nm23) in solid tumours. Eur J Cancer. 1991;27(10):1302–1307. doi: 10.1016/0277-5379(91)90101-i. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Leone A., Flatow U., VanHoutte K., Steeg P. S. Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity. Oncogene. 1993 Sep;8(9):2325–2333. [PubMed] [Google Scholar]
  17. Luo W., Matsuo K., Nagayama Y., Urano T., Furukawa K., Takeshita A., Nakayama T., Yokoyama N., Yamashita S., Izumi M. Immunohistochemical analysis of expression of nm23-H1/nucleoside diphosphate kinase in human thyroid carcinomas: lack of correlation between its expression and lymph node metastasis. Thyroid. 1993 Summer;3(2):105–109. doi: 10.1089/thy.1993.3.105. [DOI] [PubMed] [Google Scholar]
  18. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966 Mar;50(3):163–170. [PubMed] [Google Scholar]
  19. Nakayama H., Yasui W., Yokozaki H., Tahara E. Reduced expression of nm23 is associated with metastasis of human gastric carcinomas. Jpn J Cancer Res. 1993 Feb;84(2):184–190. doi: 10.1111/j.1349-7006.1993.tb02853.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakayama T., Ohtsuru A., Nakao K., Shima M., Nakata K., Watanabe K., Ishii N., Kimura N., Nagataki S. Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. J Natl Cancer Inst. 1992 Sep 2;84(17):1349–1354. doi: 10.1093/jnci/84.17.1349. [DOI] [PubMed] [Google Scholar]
  21. Okabe-Kado J., Kasukabe T., Honma Y., Hayashi M., Henzel W. J., Hozumi M. Identity of a differentiation inhibiting factor for mouse myeloid leukemia cells with NM23/nucleoside diphosphate kinase. Biochem Biophys Res Commun. 1992 Feb 14;182(3):987–994. doi: 10.1016/0006-291x(92)91829-f. [DOI] [PubMed] [Google Scholar]
  22. Postel E. H., Berberich S. J., Flint S. J., Ferrone C. A. Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science. 1993 Jul 23;261(5120):478–480. doi: 10.1126/science.8392752. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Royds J. A., Stephenson T. J., Rees R. C., Shorthouse A. J., Silcocks P. B. Nm23 protein expression in ductal in situ and invasive human breast carcinoma. J Natl Cancer Inst. 1993 May 5;85(9):727–731. doi: 10.1093/jnci/85.9.727. [DOI] [PubMed] [Google Scholar]
  25. Sastre-Garau X., Lacombe M. L., Jouve M., Véron M., Magdelénat H. Nucleoside diphosphate kinase/NM23 expression in breast cancer: lack of correlation with lymph-node metastasis. Int J Cancer. 1992 Feb 20;50(4):533–538. doi: 10.1002/ijc.2910500406. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Steeg P. S., de la Rosa A., Flatow U., MacDonald N. J., Benedict M., Leone A. Nm23 and breast cancer metastasis. Breast Cancer Res Treat. 1993;25(2):175–187. doi: 10.1007/BF00662142. [DOI] [PubMed] [Google Scholar]
  29. Teng D. H., Engele C. M., Venkatesh T. R. A product of the prune locus of Drosophila is similar to mammalian GTPase-activating protein. Nature. 1991 Oct 3;353(6343):437–440. doi: 10.1038/353437a0. [DOI] [PubMed] [Google Scholar]
  30. Tokunaga Y., Urano T., Furukawa K., Kondo H., Kanematsu T., Shiku H. Reduced expression of nm23-H1, but not of nm23-H2, is concordant with the frequency of lymph-node metastasis of human breast cancer. Int J Cancer. 1993 Aug 19;55(1):66–71. doi: 10.1002/ijc.2910550113. [DOI] [PubMed] [Google Scholar]
  31. Urano T., Furukawa K., Shiku H. Expression of nm23/NDP kinase proteins on the cell surface. Oncogene. 1993 May;8(5):1371–1376. [PubMed] [Google Scholar]
  32. 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]

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