Medical Oncology

, Volume 19, Issue 4, pp 239–248 | Cite as

Clinical significance of nm23 expression and chromosome 17 numerical aberrations in primary gastric cancer

  • Ryusuke Terada
  • Toru Yasutake
  • Shirou Nakamura
  • Takashi Hisamatsu
  • Terumitsu Sawai
  • Hiroyuki Yamaguchi
  • Tohru Nakagoe
  • Hiroyoshi Ayabe
  • Yutaka Tagawa
Original Article


The metastasis suppressor gene nm23 located on chromosome 17 might be one of the targets in deletions of chromosome 17. In this study, we analyzed the expression of nm23 and chromsome 17 aberrations in gastric cancer and assessed their clinicopathological and prognostic significance. In 103 gastric cancer patients, we examined nm23 expression by immunohistochemistry and detected chromosome 17 aberrations by fluorescence in situ hybridization. There was a significant difference in the expression of nm23 among differentiated histologic types (well>moderately>poorly) (p<0.01). Negative expression of nm23 correlated with depth of invasion (p<0.01), lymph node metastasis (p<0.05), lymphatic invasion (p<0.05), venous invasion (p<0.05), poor prognosis (p<0.05), and chromosome 17 loss (p<0.05). Chromosome 17 aberrations broadly correlated with clinicopathological variables and were associated with poor prognosis (p<0.05). Univariate analyses identified nm23 (p<0.05), chromosome 17 aberrations (p<0.05), tumor size (p<0.01), depth of invasion (p<0.0001), lymph node metastasis (P<0.001), hepatic metastasis (p<0.01), peritoneal dissemination (p<0.01), and lymphatic invasion (p<0.01) as significant prognostic factors. Multivariate analysis showed that expression of nm23 and chromosome 17 aberrations were not independent prognostic indicators. Our results indicate that negative expression of nm23 and chromosome 17 numerical aberrations correlate with tumor progression and poor prognosis but are not independent prognostic indicators.

Key Words

Gastric cancer nm23 chromosome 17 immunohistochemistry fluorescence in situ hybridization (FISH) 


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  1. 1.
    Tagawa, Y., Yasutake, T., Sawai, T., Nanashima, A., Jibiki, M., Morinaga, M., et al. (1997). Clinical and pathological significance of numerical aberrations of chromosomes 11 and 17 in colorectal neoplasms. Clin. Cancer Res. 3:1587–1592.PubMedGoogle Scholar
  2. 2.
    Rao, P.H., Mathew, S., Lauwers, G., Rodriguez, E., Kelsen, D.P. and Chaganti, R.S. (1993). Interphase cytogenetics of gastric and esophageal adenocarcinomas. Diagn. Mol. Pathol. 2:264–268.PubMedGoogle Scholar
  3. 3.
    Micale, M.A., Visscher, D.W., Gulino, S. and Wolman, S.R. (1994). Chromosomal aneuploidy in proliferative breast disease. Hum. Pathol. 25:29–35.PubMedCrossRefGoogle Scholar
  4. 4.
    Gomyo, Y., Osaki, M., Kaibara, N. and Ito, H. (1996). Numerical aberration and point mutation of p53 gene in human gastric intestinal metaplasia and well-differentiated adenocarcinoma: analysis by fluorescence in situ hybridization (FISH) and PCR-SSCP. Int. J. Cancer 66:594–599.PubMedCrossRefGoogle Scholar
  5. 5.
    Terada, R., Yasutake, T., Yamaguchi, E., Hisamatsu, T., Nakamura, S., Ayabe, H., et al. (1999). Higher frequencies of numerical aberrations of chromosome 17 in primary gastric cancers are associated with lymph node metastasis. J. Gastroenterol. 34:11–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Terada, R., Yasutake, T., Nakamura, S., Hisamatsu, T., Nakagoe, T., Ayabe, H., et al. (2001). Evaluation of metastatic potential of gastric tumors by staining for proliferating cell nuclear antigen and chromosome 17 numerical aberrations. Ann. Surg. Oncol. 8:525–532.PubMedCrossRefGoogle Scholar
  7. 7.
    Kobayashi, M., Kawashima, A., Mai, M. and Ooi, A. (1996). Analysis of Chromosome 17p13 (p53 locus) alterations in gastric carcinoma cells by dual-color fluorescence in situ h ybridization. Am. J. Pathol. 149:1575–1584.PubMedGoogle Scholar
  8. 8.
    Laurent-Puig, P., Olschwang, S., Delattre, O., Remvikos, Y., Asselain, B., Melot, T., et al. (1992). Survival and acquired genetic alterations in colorectal cancer. Gastroenterology 102:1136–1141.PubMedGoogle Scholar
  9. 9.
    Steeg, P.S., Bevilacqua, G., Kopper, L., Thorgeirsson, U.P., Talmadge, J.E., Liotta, L.A., et al. (1988). Evidence for a novel gene associated with low tumor metastatic potential. J. Natl. Cancer Inst. 80:200–204.PubMedCrossRefGoogle Scholar
  10. 10.
    Gilles, A.M., Prescan, E., Vonica, A. and Lascu, I. (1991). Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J. Biol. Chem. 266:8784–8789.PubMedGoogle Scholar
  11. 11.
    Steeg, P.S., Bevilacqua, G., Pozzatti, R., Kopper, L., Liotta, L.A. and Sobel, M.E. (1988). Altered expression of nm23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis. Cancer Res. 48:6550–6554.PubMedGoogle Scholar
  12. 12.
    Bevilacqua, G., Sobel, M.E., Liotta, L.A. and Steeg, P.S. (1989). Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinoma with lymph node involvement and other histopathological indicators of high tumor metastatic potential. Cancer Res. 49:5185–5190.PubMedGoogle Scholar
  13. 13.
    Yamaguchi, A., Urano, T., Goi, T., Takeuchi, K., Niimoto, S., Nakagawara, G., et al. (1994). Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma. Cancer 73:2280–2284.PubMedCrossRefGoogle Scholar
  14. 14.
    Dome, B., Somlai, B. and Timar, J. (2000). The loss of NM23 protein in malignant melanoma predicts lymphatic spread without affecting survival. Anticancer Res. 20:3971–3974.PubMedGoogle Scholar
  15. 15.
    Mandai, M., Konishi, I., Koshiyama, M., Mori, T., Arao, S., Tashiro, H., et al. (1994). Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. Cancer Res. 54:1825–1830.PubMedGoogle Scholar
  16. 16.
    Nakayama, H., Yasui, W., Yokozaki, H. and Tahara, E. (1993). Reduced expression of nm23 is associated with metastasis of human gastric carcinomas. Jpn. J. Cancer Res. 84:184–190.PubMedGoogle Scholar
  17. 17.
    Japanese Gastric Cancer Association (1999). Japanese Classification of Gastric Carcinoma, 13th ed., pp1–155, Kanehara, Tokyo (in Japanese).Google Scholar
  18. 18.
    Royds, J.A., Stephenson, T., Rees, R.C., Shorthouse, A.J. and Silicocks, P.B. (1993). Nm23 protein expression in ductal in situ and invasive human breast carcinoma. J. Natl. Cancer Inst. 85:727–731.PubMedCrossRefGoogle Scholar
  19. 19.
    Pinkel, D., Straume, T. and Gray, J.W. (1986). Cytogenic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc. Natl. Acad. Sci. USA 83:2934–2938.PubMedCrossRefGoogle Scholar
  20. 20.
    Hopman, A.H.N., Moesker, O., Smeets, W.G.B., Pauwels, P.E., Vooijs, G.P. and Ramaekers, C.S. (1991). Numerical chromosome 1,7,9, and 11 aberrations in bladder cancer detected by in situ hybridization. Cancer Res. 51:644–651.PubMedGoogle Scholar
  21. 21.
    Sauter, G., Deng, G., Moch, H., Kerschmann, R., Matsumura, K., De Vries, S. et al. (1994). Physical deletion of the p53 gene in bladder cancer. Am. J. Pathol. 144:756–766.PubMedGoogle Scholar
  22. 22.
    Sauter, G., Moch, H., Moore, D., Carroll, P., Kerschmann, R., Chew, K., et al. (1993). Heterogeneity of erbB-2 gene amplification in bladder cancer. Cancer Res. 53:2199–2203.PubMedGoogle Scholar
  23. 23.
    Cohn, K.H., Wang, F.S., Desoto LaPaix, F., Solomon, W.B., Patterson, L.G., Arnold, M.R., et al. (1991). Association of nm23-H1 allelic deletions with distant metastasis in colorectal carcinoma. Lancet 338:722–724.PubMedCrossRefGoogle Scholar
  24. 24.
    Leone, A., McBride, O.W., Weston, A., Wang, M.G., Anglard, P., Cropp, C.S., et al. (1991). Somatic allelic deletion of nm23 in human cancer. Cancer Res. 51:2490–2493.PubMedGoogle Scholar
  25. 25.
    Marone, M., Scambia, G., Ferrandina, G., Giannitelli, C., Benedetti-Panici, P., Iacovella, S., et al. (1996). Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion. Br. J. Cancer 74:1063–1068.PubMedGoogle Scholar
  26. 26.
    Kawakubo, Y., Sato, Y., Koh, T., Kono, H. and Kameya, T. (1997). Expression of nm23 protein in pulmonary adenocarcinomas: inverse correlation to tumor progression. Lung Cancer 17:103–113.PubMedCrossRefGoogle Scholar
  27. 27.
    Sauer, T., Furu, I., Beraki, K., Jebsen, P.W., Ormerod, E. and Naess, O. (1998). Nm23 protein expression in fine-needle aspirates from breast carcinoma: inverse correlation with cytologic grading, lymph node status, and ploidy. Cancer 84:109–114.PubMedCrossRefGoogle Scholar
  28. 28.
    Müller, W., Schneider, A., Hommel, G. and Gabbert, H.E. (1998). Expression of nm23 in gastric carcinoma: association with tumor progression and poor prognosis. Cancer 83:2481–2487.PubMedCrossRefGoogle Scholar
  29. 29.
    Kodera, Y., Isobe, K., Yamaguchi, M., Kondoh, K., Kimura, N., Pharm, D., et al. (1994). Expression of nm23 H-1 RNA levels in human gastric cancer tissues—a negative correlation with nodal metastasis. Cancer 73:259–265.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Ryusuke Terada
    • 1
    • 3
  • Toru Yasutake
    • 1
  • Shirou Nakamura
    • 1
  • Takashi Hisamatsu
    • 1
  • Terumitsu Sawai
    • 1
  • Hiroyuki Yamaguchi
    • 1
  • Tohru Nakagoe
    • 1
  • Hiroyoshi Ayabe
    • 1
  • Yutaka Tagawa
    • 2
  1. 1.The First Department of SurgerySchool of MedicineJapan
  2. 2.School of Health SciencesNagasaki UniversityNagasaki City, NagasakiJapan
  3. 3.Department of SurgeryHokusho Central HospitalNagasakiJapan

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