Skip to main content
PMC home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Oct;84(10):1072–1077. doi: 10.1111/j.1349-7006.1993.tb02803.x

Comparative Immunohistochemical Studies of p53 and Proliferating Cell Nuclear Antigen Expression and Argyrophilic Nucleolar Organizer Regions in Pancreatic Duct Cell Carcinomas

Tadamichi Suzuki 1, Yasuo Takano 1,✉
PMCID: PMC5919065  PMID: 7901190

Abstract

Thirty‐eight cases of pancreatic duct cell carcinoma were examined for p53 expression and proliferating cell nuclear antigen (PCNA) by enhanced immunohistochemistry, as well as for changes in numbers of argyrophilic nucleolar organizer regions (AgNORs). Fifteen cases (39.5%) showed p53 overexpression, which tended to increase in proportion to the histopathological grading of malignancy. However, tumor stage and lymph node status were not correlated to p53 overexpression. PCNA labeling index (LI) increased with both histologically malignant grading and pathological stage, but was not correlated with lymph node status. The expressions of p53 and PCNA thus did not necessarily reflect the degree of malignant development. In contrast, AgNOR number showed statistically significant correlations with these three indicators of malignancy. A comparative analysis of p53, PCNA LI and AgNOR number showed overexpression of p53 to be correlated to PCNA LI and essentially unrelated to AgNOR number. The present results thus indicate a close relation between p53 and PCNA, while AgNORs appear to be regulated separately from either of them.

Keywords: Pancreatic cancer, p53 protein, PCNA, AgNORs, Enhanced immunohistochemistry

Full Text

The Full Text of this article is available as a PDF (500.5 KB).

REFERENCES

  • 1).Iggo , R. , Gatter , K. , Bartek , J. , Lane , D. and Harris , A. L.Increased expression of mutant forms of p53 oncogene in primary lung cancer . Lancet , 335 , 675 – 679 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 2).MacKay , J. , Elder , P. A. , Steel , C. M. , Forrest , A. P. M. and Evans , H. J.Allele loss on the short arm of chromosome 17 in breast cancers . Lancet , ii , 1384 – 1385 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 3).Varley , J. M. , Brammar , W. J. , Lane , D. P. , Swallow , J. E. , Dolan , C. and Walker , R. A.Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinomas . Oncogene , 6 , 413 – 421 ( 1991. ). [PubMed] [Google Scholar]
  • 4).Baker , S. J. , Fearon , E. R. , Nigro , J. M. , Hamilton , S. R. , Presinger , A. C. , Jessup , J. M. , van Tuinen , P. , Ledbetter , D. H. , Barker , D. F. , Nakamura , Y. , White , R. and Vogelstein , B.Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas . Science , 244 , 217 – 221 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 5).Shi , S. R. , Key , M. C. and Kalra , K. L.Antigen retrieval in formalin‐fixed, paraffin‐embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections . J. Histochem. Cytochem. , 39 , 741 – 748 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6).Morris , G. F. and Mathews , M. B.Regulation of proliferating cell nuclear antigen during the cell cycle . J. Biol. Chem. , 264 , 13856 – 13864 ( 1989. ). [PubMed] [Google Scholar]
  • 7).Mercer , W. E. , Shields , M. T. , Lin , D. , Appella , E. and Ullrich , S. J.Growth suppression induced by wild‐type p53 protein is accompanied by selective down‐regulation of proliferating‐cell nuclear antigen expression . Proc. Natl. Acad. Sci. USA , 88 , 1958 – 1962 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8).Robbins , B. A. , de la Vega , D. , Ogata , K. , Tan , E. M. and Nakamura , R. M.Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies . Arch. Pathol. Lab. Med. , 111 , 841 – 845 ( 1987. ). [PubMed] [Google Scholar]
  • 9).Hall , P. A. , Levison , D. A. , Woods , A. L. , Yu , C. C.‐W. , Kellock , D. B. , Watkins , J. A. , Barnes , D. M. , Gillett , C. E. , Camplejohn , R. , Dover , R. and Wassen , N. H.Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms . J. Pathol. , 162 , 285 – 294 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 10).Hall , P. A. and Levison , D. A.Review: Assessment of cell proliferation in histological material . J. Clin. Pathol. , 43 , 184 – 192 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11).Kida , Y. , Takano , Y. and Okudaira , M.Argyrophilic nucleolar organizer regions (AgNORs) in human adenocortical neoplasms . J. Cancer Res. Clin. Oncol. , 119 , 49 – 54 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 12).Ploton , D. , Menager , M. , Jeannesson , P. , Himber , G. , Pigeon , F. and Adent , J. J.Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer region at the optical level . Histochem. J. , 18 , 5 – 14 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 13).Dillon , W. R. and Goldstein , M. “ Multivariate Analysis: Methods and Applications ,” pp . 360 – 393 ( 1984. ). John Wiley & Sons; , New York . [Google Scholar]
  • 14).Bartek , J. , Bartkova , J. , Vojtesek , B. , Staskova , Z. , Rejthar , A. , Kovarik , J. and Lane , D. P.Patterns of expression of the p53 tumor suppressor in human breast tissues and tumours in situ and in vitro . Int. J. Cancer , 46 , 839 – 844 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 15).Walker , R. A. , Dearing , S. J. , Lane , D. P. and Varley , J. M.Expression of p53 protein in infiltrating and in‐situ breast carcinomas . J. Pathol. , 165 , 203 – 211 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 16).Visakorpi , T. , Kallioniemi , O‐P. , Heikkinen , A. , Koivula , T. and Isola , J.Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation . J. Natl. Cancer Inst. , 84 , 883 – 887 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 17).Herman , G. E. , Chlipapa , E. , Bochenski , G. , Sabin , L. and Elfont , E.Zinc formalin fixative for automated tissue processing . J. Histotechnol. , 11 , 85 – 90 ( 1988. ). [Google Scholar]
  • 18).Abbondanzo , S. L. , Allred , D. C. , Lampkin , S. and Banks , P. M.Enhancement of immunoreactivity in paraffin enbedded tissue by refixation in zinc sulfate‐formalin . Proc. Annu. Meet. US and Canadian Acad. Pathol. ( 1990. ). [PubMed] [Google Scholar]
  • 19).Banks , L. , Matlashewski , G. and Crawford , L.Isolation of human‐p53‐specific monoclonal antibodies and their use in the studies of human p53 expression . Eur. J. Biochem. , 159 , 529 – 534 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 20).Bartkova , J. , Bartek , J. , Lukas , J. , Vojtesek , B. , Staskova , Z. , Rejthar , A. , Kovarik , J. , Midgley , C. A. and Lane , D. P.p53 protein alterations in human testicular cancer including pre‐invasive intratubular germ‐cell neoplasia . Int. J. Cancer , 49 , 196 – 202 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21).Gannon , J. V. , Greaves , R. , Iggo , R. and Lane , D. P.Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form . EMBO J. , 9 , 1595 – 1602 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22).Finlay , C. A. , Hinds , P. W. , Tan , T‐H. , Eliyahu , D. , Oren , M. and Levine , A. J.Activating mutations for transformation by p53 produce a gene product that forms an hsc70‐p53 complex with an altered half‐life . Mol. Cell Biol. , 8 , 531 – 539 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23).Rodrigues , N. R. , Rowan , A. , Smith , M. E. F. , Kerr , I. B. , Bodmer , W. F. , Gannon , J. V. and Lane , D. P.p53 mutations in colorectal cancer . Proc. Natl. Acad. Sci. USA , 87 , 7555 – 7559 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24).Barton , C. M. , Staddon , S. L. , Hughes , C. M. , Hall , P. A. , O'Sullivan , C. , Kloppel , G. , Theis , B. , Russell , R. C. G. , Neoptolemus , J. , Williamson , R. C. N. , Lane , D. P. and Lemoine , N. R.Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer . Br. J. Cancer , 64 , 1076 – 1082 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25).Kawasaki , Y. , Monden , T. , Morimoto , H. , Murotani , M. , Miyoshi , Y. , Kobayashi , T. , Shimano , T. and Mori , T.Immunohistochemical study of p53 expression in microwave‐fixed, paraffin‐embedded sections of colorectal carcinoma and adenoma . Am. J. Clin. Pathol. , 97 , 244 – 249 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 26).Lane , D. P. and Benchimol , S.p53: oncogene or antioncogene ? Genes Dev. , 4 , 1 – 8 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 27).Crocker , J.Nucleolar organizer regions . Curr. Top. Pathol. , 82 , 91 – 149 ( 1990. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES