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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 Aug;85(8):840–846. doi: 10.1111/j.1349-7006.1994.tb02956.x

Immunohistochemical Analysis of nm23/NDP Kinase Expression in Human Lung Adenocarcinoma: Association with Tumor Progression in Clara Cell Type

Yuichi Ozeki 1,, Kunio Takishima 1, Gunji Mamiya 1
PMCID: PMC5919568  PMID: 7928630

Abstract

Levels of nm23‐H1/nucleoside diphosphate kinase (NDP kinase) expression have been reported to correlate inversely with mctastatic potential in some tumors but not in others. Whether or not nm23 gene product is associated with metastatic potential in lung cancer is not clear as yet. We therefore immunohistochemically examined the expression of nm23 gene products in primary lung adenocarci‐no mas according to cytologic subtypes in order to clarify the association of its expression with the clinical features of the disease. Seventy‐two (64.9%) of the 111 lung adenocarcinomas were positive for nm23 protein. In lung adenocarcinoma of Clara cell type, high levels of nm23 expression were associated with advanced pathologic stage, positive lymph node status, and poorer prognosis (P<0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that higher levels of nm23 expression are associated with tumor progression in lung adenocarcinoma of Clara cell type.

Keywords: nm23/NDP kinase, Immunohistochemistry, Lung adenocarcinoma

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REFERENCES

  • 1. ) Steeg , P. S. , Bevilacqua , G. , Kopper , L. , Thorgeirsson , U. P. , Talmadge , J. E. , Liotta , L. and Sobel , M. E.Evidence for a novel gene associated with low tumor metastatic potential . J. Natl. Cancer Inst. , 80 , 200 – 204 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Rosengard , A. M. , Krutzsch , H. C. , Shearn , A. , Biggs , J. , Barker , E. , Margulies , L , Richter , K. C. , Liotta , L , and Steeg , P.Reduced Nm23/Awd protein in tumor metastasis and aberrant Drosophila development . Nature , 342 , 117 – 180 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Bevilacqua , G. , Sobel , M. E. , Liotta , L. A. and 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. , 49 , 5185 – 5190 ( 1989. ). [PubMed] [Google Scholar]
  • 4. ) Leone , A. , Flatow , U. , King , C. R. , Sandeen , M. A. , Margulies , I. M. K. , Liotta , L. A. and Steeg , P. S.Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23—transfected melanoma cells . Cell , 65 , 25 – 35 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Hennessy , C. , Henry , J. A. , May , F. E. B. , Westley , B. R. , Angus , B. and Lennard , T. W. J.Expression of the anti‐metastatic gene nm23 in human breast cancer: an association with good prognosis . J. Natl. Cancer Inst. , 83 , 281 – 285 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) 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. and Hanash , S. M.High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N—myc gene amplification . J. Clin. Invest. , 88 , 341 – 345 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Haut , M. , Steeg , P. S. , Willson , J. K. and 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. , 83 , 712 – 716 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Higashiyama , M. , Doi , O. , Yokouchi , H. , Kodama , K. , Nakamori , S. , Tateishi , R. and Kimura , N.Immunonistochemical analysis of nm23 gene product/NDP kinase expression in pulmonary adenocarcinoma: lack of prognostic value . Br. J. Cancer , 66 , 533 – 536 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. ) Shimosato , Y. , Kodama , T. and Kameya , T.Morpho—genesis of peripheral type adenocarcinoma of the lung . In“Morphogenesis of the Lung Cancer,” Vol.1 , ed. Shimosato Y. , Melamed M. R. and Nettersheim P. pp. 65 – 89 ( 1982. ). CRC press; , Florida . [Google Scholar]
  • 10. ) The Japan Lung Cancer Society . “General Rules for Clinical and Pathological Record of Lung Cancer,” pp. 17 – 21 ( 1987. ). Kasahara Shuppan; , Tokyo ( in Japanese ). [Google Scholar]
  • 11. ) Kaplan , E. L. and Meier , P.Nonparametric estimation from incomplete observations . J. Am. Stat. Assoc. , 53 , 457 – 481 ( 1958. ). [Google Scholar]
  • 12. ) Gehan , E.A generalized Wilcoxon test for comparing arbitrarily singly censored samples . Biometrika , 52 , 203 – 224 ( 1956. ). [PubMed] [Google Scholar]
  • 13. ) Hirayama , R. , Sawai , S. , Takagi , Y. , Mishima , Y. , Kimura , N. , Shimada , N. , Esaki , Y. , Kurashima , C , Utsuyama , M. and 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. , 83 , 1249 – 1250 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Florenes , V. A. , Aamdal , S. , Myklebost , O. , Maelandsmo , G. M. , Bruland , O. S. and Fodstad , O.Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression . Cancer Res. , 52 , 6088 – 6091 ( 1992. ). [PubMed] [Google Scholar]
  • 15. ) Staml , J. A. , Leone , A. , Rosengard , A. M. , Porter , L. , King , C. R. and Steeg , P. S.Identification of a second human nm23 gene, nm23‐H2 . Cancer Res. , 51 , 445 – 449 ( 1991. ). [PubMed] [Google Scholar]
  • 16. ) Teng , D. H , Engele , C. M. and Venkatesh , T. R.A product of the prune locus of Drosophila is similar to mammalian GTPase—activating protein . Nature , 353 , 437 – 440 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Randazzo , P. A. , Northup , J. K. and Kahn , R. A.Activation of a small GTP‐binding protein by nucleoside diphosphate kinase . Science , 254 , 850 – 853 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Liotta , L. A. and Steeg , P. S.Clues to the function of Nm23 and Awd proteins in development, signal transduction, and tumor metastasis provided by studies of Dictyostelium discoideum . J. Natl. Cancer Inst. , 82 , 1170 – 1172 ( 1990. ). [DOI] [PubMed] [Google Scholar]

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