Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1992 Sep;141(3):545–550.

In situ hybridization and immunohistochemistry of p53 tumor suppressor gene in human esophageal carcinoma.

H Sasano 1, Y Goukon 1, T Nishihira 1, H Nagura 1
PMCID: PMC1886688  PMID: 1519662

Abstract

We have studied expression of p53, a tumor suppressor gene, by using both immunohistochemistry and in situ hybridization in 20 cases of squamous cell carcinoma of the esophagus. Immunohistochemical analysis was performed by using monoclonal antibody pAb1801. Immunoreactive p53 was observed in the nuclei of the tumor cells in 17 cases. We used 35S-labeled anti-sense single-stranded synthetic oligonucleotide probe ON102, which hybridized with DNA sequence near the 5' end of p53, for in situ hybridization. In all the cases of invasive squamous cell carcinoma studied, no significant accumulation of p53 hybridization signals was observed in carcinoma cells. This result indicates that overexpression of p53 observed by immunohistochemical staining is not due to an increase in the steady-state level of p53 mRNA in frank carcinoma cells. In six cases of morphologically normal esophageal mucosa distant from carcinoma, accumulation of hybridization signals was observed in basal and parabasal cells of the mucosa. The mucosa of these cases was negative for p53 immunoreactivity except for one case showing sporadic positivity. Accumulation of hybridization signals was observed in foci of squamous dysplasia not associated with invasion in three cases.

Full text

PDF
545

Images in this article

548Figure 1
on p.548
548Figure 2
on p.548
549Figure 3
on p.549

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banks L., Matlashewski G., Crawford L. Isolation of human-p53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem. 1986 Sep 15;159(3):529–534. doi: 10.1111/j.1432-1033.1986.tb09919.x. [DOI] [PubMed] [Google Scholar]
  2. Blount P. L., Ramel S., Raskind W. H., Haggitt R. C., Sanchez C. A., Dean P. J., Rabinovitch P. S., Reid B. J. 17p allelic deletions and p53 protein overexpression in Barrett's adenocarcinoma. Cancer Res. 1991 Oct 15;51(20):5482–5486. [PubMed] [Google Scholar]
  3. Casson A. G., Mukhopadhyay T., Cleary K. R., Ro J. Y., Levin B., Roth J. A. p53 gene mutations in Barrett's epithelium and esophageal cancer. Cancer Res. 1991 Aug 15;51(16):4495–4499. [PubMed] [Google Scholar]
  4. Couwenhoven R. I., Luo W., Snead M. L. Co-localization of EGF transcripts and peptides by combined immunohistochemistry and in situ hybridization. J Histochem Cytochem. 1990 Dec;38(12):1853–1857. doi: 10.1177/38.12.2254649. [DOI] [PubMed] [Google Scholar]
  5. D'Amico D., Carbone D., Mitsudomi T., Nau M., Fedorko J., Russell E., Johnson B., Buchhagen D., Bodner S., Phelps R. High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene. 1992 Feb;7(2):339–346. [PubMed] [Google Scholar]
  6. Davidoff A. M., Humphrey P. A., Iglehart J. D., Marks J. R. Genetic basis for p53 overexpression in human breast cancer. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5006–5010. doi: 10.1073/pnas.88.11.5006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., 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. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hayashi M., Ninomiya Y., Parsons J., Hayashi K., Olsen B. R., Trelstad R. L. Differential localization of mRNAs of collagen types I and II in chick fibroblasts, chondrocytes, and corneal cells by in situ hybridization using cDNA probes. J Cell Biol. 1986 Jun;102(6):2302–2309. doi: 10.1083/jcb.102.6.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hollstein M. C., Metcalf R. A., Welsh J. A., Montesano R., Harris C. C. Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9958–9961. doi: 10.1073/pnas.87.24.9958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Iggo R., Gatter K., Bartek J., Lane D., Harris A. L. Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet. 1990 Mar 24;335(8691):675–679. doi: 10.1016/0140-6736(90)90801-b. [DOI] [PubMed] [Google Scholar]
  11. Ledinko N., Costantino R. L. Modulation of p53 gene expression and cytokeratin 18 in retinoid-mediated invasion suppressed lung carcinoma cells. Anticancer Res. 1990 Sep-Oct;10(5A):1335–1339. [PubMed] [Google Scholar]
  12. Marks J. R., Davidoff A. M., Kerns B. J., Humphrey P. A., Pence J. C., Dodge R. K., Clarke-Pearson D. L., Iglehart J. D., Bast R. C., Jr, Berchuck A. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res. 1991 Jun 1;51(11):2979–2984. [PubMed] [Google Scholar]
  13. Meltzer S. J., Yin J., Huang Y., McDaniel T. K., Newkirk C., Iseri O., Vogelstein B., Resau J. H. Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4976–4980. doi: 10.1073/pnas.88.11.4976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mercer W. E., Avignolo C., Baserga R. Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies. Mol Cell Biol. 1984 Feb;4(2):276–281. doi: 10.1128/mcb.4.2.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  16. Parada L. F., Land H., Weinberg R. A., Wolf D., Rotter V. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature. 1984 Dec 13;312(5995):649–651. doi: 10.1038/312649a0. [DOI] [PubMed] [Google Scholar]
  17. Puisieux A., Lim S., Groopman J., Ozturk M. Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens. Cancer Res. 1991 Nov 15;51(22):6185–6189. [PubMed] [Google Scholar]
  18. Purdie C. A., O'Grady J., Piris J., Wyllie A. H., Bird C. C. p53 expression in colorectal tumors. Am J Pathol. 1991 Apr;138(4):807–813. [PMC free article] [PubMed] [Google Scholar]
  19. Reich N. C., Levine A. J. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells. Nature. 1984 Mar 8;308(5955):199–201. doi: 10.1038/308199a0. [DOI] [PubMed] [Google Scholar]
  20. Rogel A., Popliker M., Webb C. G., Oren M. p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors. Mol Cell Biol. 1985 Oct;5(10):2851–2855. doi: 10.1128/mcb.5.10.2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sasano H., Miyazaki S., Sawai T., Sasano N., Nagura H., Funahashi H., Aiba M., Demura H. Primary pigmented nodular adrenocortical disease (PPNAD): immunohistochemical and in situ hybridization analysis of steroidogenic enzymes in eight cases. Mod Pathol. 1992 Jan;5(1):23–29. [PubMed] [Google Scholar]
  22. Takahashi T., Nau M. M., Chiba I., Birrer M. J., Rosenberg R. K., Vinocour M., Levitt M., Pass H., Gazdar A. F., Minna J. D. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989 Oct 27;246(4929):491–494. doi: 10.1126/science.2554494. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES