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Immunohistochemical analysis of nm23 protein expression in malignant bone tumors

  • Original Paper
  • Clinical Oncology
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Abstract

Expression levels of nm23 protein in 72 malignant bone tumors comprising 41 osteosarcomas, 22 chondrosarcomas, 6 Ewing's sarcomas, and 2 malignant fibrous histiocytomas were examined immunohistochemically, using anti-nm23 protein polyclonal antibody, and compared with 51 cases of benign bone tumors or tumor-like lesions. Malignant bone tumors showed significantly higher nm23 protein expression than benign bone tumors or tumor-like lesions (P<0.0001). In chondrosarcoma, nm23 expression increased in high-grade tumors (grade I versus grade II and III:P=0.0229). In the cases of osteosarcoma, however, grade IV osteosarcomas showed decreased expression of nm23 compared with grade III tumors (P=0.0122). There was no significant relationship between nm23 expression and histological type. nm23 expression had no correlation with metastatic potential in osteosarcoma, although the therapy was not uniform in our cases. Furthermore, in 6 cases of osteosarcoma and 1 case of Ewing's sarcoma, there was no clear tendency for a decrease of nm23 in the metastatic sites compared with primary sites, as reported in breast cancer. These results showed that, in contrast to reports on breast cancer and experimental models, nm23 protein expression in human bone tumors may be associated with malignant potentiality, except in cases of osteosarcoma.

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References

  • Arai T, Watanabe M, Onodera M, Yamashita T, Masunaga A, Itoyama S, Itoh K, Sugawara I (1993) Reduced nm23-H1 messenger RNA expression in metastatic lymph nodes from patients with papillary carcinoma of the thyroid. Am J Pathol 142: 1938–1944

    PubMed  Google Scholar 

  • Ayhan A, Yasui W, Yokozaki H Kitadai Y, Tahara E (1993) Reduced expression of nm23 protein is associated with advanced tumor stage and distant metastases in human colorectal carcinomas. Virchows Arch [B] 63: 213–218

    Google Scholar 

  • Barnes R, Masood S, Barker E, Rosengard AM, Coggin DL, Crowell T, King CR, Porter-Jorddan K, Wargotz ES, Liotta LA, Steeg PS (1991) Low nm23 protein expression in infiltrating ductal breast carcinomas with reduced patients survivals. Am J Pathol 139: 245–250

    PubMed  Google Scholar 

  • Bauer HC, Kreicbergs A, Silfversward C (1989) Prognostication including DNA analysis in osteosarcoma. Acta Orthop Scand 60: 353–360

    PubMed  Google Scholar 

  • Bertheau P, De La Rosa A, Steeg PS, Merino MJ (1994) nm23 protein in neoplastic and nonneoplastic thyroid tissues. Am J Pathol 145: 26–32

    PubMed  Google Scholar 

  • Bevilacqua G, Sobel ME, Liotta L, Steeg PS (1989) Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinoma indicates of high tumor metastatic potential. Cancer Res 49: 5185–5190

    PubMed  Google Scholar 

  • Boix L, Bruix J, Campo E, Sole M, Castells A, Fuster J, Rivera F, Cardesa A, Rodes J (1994) nm23-H1 expression and disease recurrence after surgical resection of small hepatocellular carcinoma. Gastroenterology 107: 486–491

    PubMed  Google Scholar 

  • Dorfman H, Weiss S (1984) Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low grade osteosarcoma. Semin Diagn Pathol 1: 215–234

    PubMed  Google Scholar 

  • Evans HL, Ayala AG, Romsdahl MM (1977) Prognostic factors in chondrosarcoma of bone. A clinicopathologic analysis with emphasis on histologic grading. Cancer 40: 818–831

    PubMed  Google Scholar 

  • Farley DR, Eberhardt NL, Grant CS, Schaid DJ, Van-Heerden JA, Hay ID, Khosla S (1993) Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms. World J Surg 17: 615–621

    PubMed  Google Scholar 

  • Florenes VA, Aamdal S, Myklebost O, Maelandsmo GM, Bruland OS, Fodstad O (1992) Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res 52: 6088–6091

    PubMed  Google Scholar 

  • Gilles AM, Presecan E, Vonica A, 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

    PubMed  Google Scholar 

  • Haut M, Steeg PS, Willson JKV, Markowitz SD (1991) 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 83: 712–716

    PubMed  Google Scholar 

  • Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, Reynolds CP, Seeger RC, Lottspeich F, Strahler JR, Hanash SM (1991) High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage and with N-myc gene amplification. J Clin Invest 88: 341–345

    PubMed  Google Scholar 

  • Hennessy C, Henry JA, May FEB, Westley BR, Angus B, Lennard TWJ (1991) Expression of the antimetastatic gene nm23 in human breast cancer: An association with good prognosis. J Natl Cancer Inst 83: 281–285

    PubMed  Google Scholar 

  • Higashiyama M, Doi O, Yokoguchi H, Kamada K, Nakamori S, Tateishi R, Kimura N (1992) Immunohistochemical analysis of nm23 gene product/NDP kinase expression in pulmonary adenocarcinoma: lack of prognostic value. Br J Cancer 66: 533–536

    PubMed  Google Scholar 

  • Hirayama R, Sawai S, Takagi Y, Mishima Y, Kimura N, Shimada N, Esaki Y, Kurashima C, Utsuyama M, Hirokawa K (1991) 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 83: 1249–1250

    PubMed  Google Scholar 

  • Honoki K, Tsutsumi M, Miyauchi M, Mii Y, Tsujiuchi T, Moroshita T, Miura S, Aoki M, Kobayashi E, Tamai S, et al (1993) Increased expression of nucleoside diphosphate kinase/nm23 and c-Ha-ras mRNA is associated with spontanous lung metastasis in rattransplantable osteosarcomas. Cancer Res 53: 5038–5042

    PubMed  Google Scholar 

  • Keim D, Hailat N, Melhen R, Zhu XX, Lascu I, Veron M, Strahler J (1992) Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase. J Clin Invest 89: 919–924

    PubMed  Google Scholar 

  • Kobayashi S, Iwase H, Itoh Y, Furukawa H, Yamashita H, Kuzushima T, Iwata H, Masaoka A, Kimura N (1992) Estrogen receptor, c-erb B-2 and nm23/NDP kinase expression in intraductal and invasive components of human breast cancers. Jpn J Cancer Res 83: 859–865

    PubMed  Google Scholar 

  • Kodera Y, Isobe K, Yamauchi M, Kondoh K, Kimura N, Akiyama S, Itoh K, Nakashima I, Takagi H (1994) Expression of nm23 H-1 RNA levels in human gastric cancer tissues. A negative correlation with nodal metastasis. Cancer 73: 259–265

    PubMed  Google Scholar 

  • Konishi N, Nakaoka S, Tsuzuki T, Matsumoto K, Kitahori Y, Hiasa Y, Urano T, Shiku H (1993) Expression of nm23-H1 and nm23-H2 proteins in prostate carcinoma. Jpn J Cancer Res 84: 1050–1054

    PubMed  Google Scholar 

  • Lacombe ML, Sastre-Garau X, Lascu I, Vonica A, Wallet V, Thiery JP, Veron M (1991) Overexpression of nucleoside diphosphate kinase (Nm23) in solid tumours. Eur J Cancer 27: 1302–1307

    PubMed  Google Scholar 

  • Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336

    PubMed  Google Scholar 

  • Luo W, Matsuo K, Nagayama Y, Urano T, Furukawa K, Takeshita A, Nakayama T, Yokoyama N, Yamashita S, Izumi M, Shiku H, Nagataki S (1993) 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 3: 105–109

    PubMed  Google Scholar 

  • Nakamori S, Ishikawa O, Ohigashi H, Imaoka S, Sasaki Y, Kameyama M, Kabuto T, Furukawa H, Iwanaga T, Kimura N (1993a) Clinicopathological features and prognostic significance of nucleoside diphosphate kinase/nm23 gene product in human pancreatic exocrine neoplasms. Int J Pancreatol 14: 125–133

    PubMed  Google Scholar 

  • Nakamori S, Ishikawa O, Ohhigashi H, Kameyama M, Furukawa H, Sasaki Y, Inaji H, Higashiyama M, Imaoka S, Iwanaga T, Funai H, Wada A, Kimura N (1993b) Expression of nucleoside diphosphate kinase/nm23 gene product in human pancreatic cancer. Clin Exp Metastasis 11: 151–158

    PubMed  Google Scholar 

  • Nakayama H, Yasui W, Yokozaki H, Tahara E (1993) Reduced expression of nm23 is associated with metastasis of human gastric carcinomas. Jpn J Cancer Res 84: 184–190

    PubMed  Google Scholar 

  • Nakayama T, Ohtsuru A, Nakao K, Shima M, Nakata K, Watanabe K, Ishii N, Kimura N, Nagataki S (1992) Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. J Natl Cancer Inst 84: 1349–1354

    PubMed  Google Scholar 

  • Rosengard AM, Kurtzsch HC, Shearn A, et al (1989) Reduced Nm23/Awd protein in tumor metastasis and aberrantDrosophila development. Nature 342: 177–180

    PubMed  Google Scholar 

  • Royds JA, Stephanson TJ, Rees RC, Shorthouse AJ, Silcocks PB (1993) Nm23 protein expression in ductal in situ and invasive human breast carcinoma. J Natl Cancer Inst 85: 727–731

    PubMed  Google Scholar 

  • Sastre-Garau X, Lacombe ML, Jouve M, Veron M, Magdelenat H (1992) Nucleoside diphosphate kinase/nm23 expression in breast cancer: Lack of correlation with lymph-node metastasis. Int J Cancer 50: 533–538

    PubMed  Google Scholar 

  • Simpson JF, O'Malley F, Dupont WD, Page DL (1994) Heterogeneous expression of nm23 gene product in noninvasive breast carcinoma. Cancer 73: 2352–2358

    PubMed  Google Scholar 

  • Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson U, Thalmadge E, Liotta LA, Sobel ME (1988a) Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80: 200–204

    PubMed  Google Scholar 

  • Steeg PS, Bevilacqua G, Pozatti R, Liotta L, Sobel ME (1988b) 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

    PubMed  Google Scholar 

  • Stephenson TJ, Royds JA, Bleehen SS, Silcocks PB, Rees RC (1993) Anti-metastatic nm23 gene product expression in keratoacanthoma and squamous cell carcinoma. Dermatology 187: 95–99

    PubMed  Google Scholar 

  • Tokunaga Y, Urano T, Furukawa K, Kondo H, Kanematsu T, Shiku H (1993) Reduced expression of nm23-H1, but not of nm23-H2, is concordant with the frequency of lymph-node metastasis of human breast cancer. Int Cancer 55: 66–71

    Google Scholar 

  • Unni KK, Dahlin DC (1984) Grading of bone tumors. Semin Diagn Pathol 1: 165–172

    Google Scholar 

  • Wallet V, Mutzel R, Troll H, Barzu O, Wurster B, Veron M, Lacombe ML (1990) Dicrostelium nucleoside diphosphatase kinase highly homologous to nm23 and awd proteins involved in mammalian tumor metastasis andDrosophila development. J Natl Cancer Inst 82: 1199–1202

    PubMed  Google Scholar 

  • Yamaguchi A, Urano T, Goi T, Takeuchi K, Niimoto S, Nakagawara G, Furukawa K, Shiku H (1994) Expression of human nm23-H1 and nm23 H-2 proteins in hepatocellular carcinoma. Cancer 73: 2280–2284

    PubMed  Google Scholar 

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Oda, Y., Walter, H., Radig, K. et al. Immunohistochemical analysis of nm23 protein expression in malignant bone tumors. J Cancer Res Clin Oncol 121, 667–673 (1995). https://doi.org/10.1007/BF01218525

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  • DOI: https://doi.org/10.1007/BF01218525

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