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Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1993 Dec;46(12):1093–1096. doi: 10.1136/jcp.46.12.1093

p53 expression in oat and non-oat small cell lung carcinomas: correlations with proliferating cell nuclear antigen.

P Korkolopoulou 1, J Oates 1, J Crocker 1, C Edwards 1
PMCID: PMC501717  PMID: 7904273

Abstract

AIMS--To investigate the immunohistochemical expression of p53 protein in small cell lung carcinoma (SCLC), comparing it with that in non-small cell carcinoma (NSCLC); and to evaluate the correlation between p53 and proliferating cell nuclear antigen (PCNA) expression as well as between p53 and PCNA expression and survival. METHODS--Paraffin wax embedded tissues from 61 cases of primary lung carcinoma were stained for p53 protein and PCNA using the monoclonal antibodies 1801 and PC-10, respectively, in a standard avidin-biotin immunoperoxidase method. RESULTS--Of the 61 lung carcinomas 35 (57%) were positive for p53 (range 1% to 90%). Ninety percent of the non-oat SCLC contained positive cells and the labelling index (LI) was significantly higher than that of the oat SCLC (p < 0.001). SLCC also displayed a higher p53 LI than NSCLC (p < 0.01); no difference was found between squamous carcinoma, adenocarcinoma, and oat cell carcinoma. A p53 LI of greater than 1% tended to be associated with nodal metastases (p < 0.05), and p53 expression in node positive tumours as well as in oat cell carcinomas was indicative of poorer survival (p < 0.01 and p < 0.1, respectively). A p53 Li of greater than 60% was a negative prognostic factor in non-oat SCLC (p < 0.05). PCNA LI was highest in non-oat SCLC and lowest in NSCLC; oat cell carcinomas had a mean LI intermediate between NSCLC and non-oat SCLC (NSCLC v oat cell carcinoma p < 0.05 and oat cell v non-oat cell carcinomas p < 0.01). A PCNA LI was not correlated with nodal metastases or survival, but there was a significant positive correlation between PCNA LI and p53 LI (rs = 0.484, p < 0.001). CONCLUSIONS--p53 and PCNA expression differ substantially among the various types of lung carcinomas. Substantial differences were also found between oat and non-oat types of SCLC, indicating that SCLC is heterogeneous as far as proliferation rate and altered p53 expression is concerned. p53 seems to be of some prognostic value. The relation between PCNA and p53 expression indicates that the PCNA gene is slightly upregulated by p53.

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  1. Barbareschi M., Girlando S., Mauri F. A., Arrigoni G., Laurino L., Dalla Palma P., Doglioni C. Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms. J Pathol. 1992 Apr;166(4):343–350. doi: 10.1002/path.1711660405. [DOI] [PubMed] [Google Scholar]
  2. Barbareschi M., Iuzzolino P., Pennella A., Allegranza A., Arrigoni G., Dalla Palma P., Doglioni C. p53 protein expression in central nervous system neoplasms. J Clin Pathol. 1992 Jul;45(7):583–586. doi: 10.1136/jcp.45.7.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caamano J., Ruggeri B., Momiki S., Sickler A., Zhang S. Y., Klein-Szanto A. J. Detection of p53 in primary lung tumors and nonsmall cell lung carcinoma cell lines. Am J Pathol. 1991 Oct;139(4):839–845. [PMC free article] [PubMed] [Google Scholar]
  4. Carey F. A., Fabbroni G., Lamb D. Expression of proliferating cell nuclear antigen in lung cancer: a systematic study and correlation with DNA ploidy. Histopathology. 1992 Jun;20(6):499–503. doi: 10.1111/j.1365-2559.1992.tb01034.x. [DOI] [PubMed] [Google Scholar]
  5. Chiba I., Takahashi T., Nau M. M., D'Amico D., Curiel D. T., Mitsudomi T., Buchhagen D. L., Carbone D., Piantadosi S., Koga H. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603–1610. [PubMed] [Google Scholar]
  6. 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]
  7. Deb S., Jackson C. T., Subler M. A., Martin D. W. Modulation of cellular and viral promoters by mutant human p53 proteins found in tumor cells. J Virol. 1992 Oct;66(10):6164–6170. doi: 10.1128/jvi.66.10.6164-6170.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fontanini G., Macchiarini P., Pepe S., Ruggiero A., Hardin M., Bigini D., Vignati S., Pingitore R., Angeletti C. A. The expression of proliferating cell nuclear antigen in paraffin sections of peripheral, node-negative non-small cell lung cancer. Cancer. 1992 Sep 15;70(6):1520–1527. doi: 10.1002/1097-0142(19920915)70:6<1520::aid-cncr2820700613>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  9. Hall P. A., Levison D. A., Woods A. L., Yu C. C., Kellock D. B., Watkins J. A., Barnes D. M., Gillett C. E., Camplejohn R., Dover R. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol. 1990 Dec;162(4):285–294. doi: 10.1002/path.1711620403. [DOI] [PubMed] [Google Scholar]
  10. Hiyoshi H., Matsuno Y., Kato H., Shimosato Y., Hirohashi S. Clinicopathological significance of nuclear accumulation of tumor suppressor gene p53 product in primary lung cancer. Jpn J Cancer Res. 1992 Jan;83(1):101–106. doi: 10.1111/j.1349-7006.1992.tb02358.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kishimoto Y., Murakami Y., Shiraishi M., Hayashi K., Sekiya T. Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. Cancer Res. 1992 Sep 1;52(17):4799–4804. [PubMed] [Google Scholar]
  14. Leonardi E., Girlando S., Serio G., Mauri F. A., Perrone G., Scampini S., Dalla Palma P., Barbareschi M. PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables. J Clin Pathol. 1992 May;45(5):416–419. doi: 10.1136/jcp.45.5.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lindberg I., Lincoln B., Rhodes C. J. Fluorometric assay of a calcium-dependent, paired-basic processing endopeptidase present in insulinoma granules. Biochem Biophys Res Commun. 1992 Feb 28;183(1):1–7. doi: 10.1016/0006-291x(92)91599-l. [DOI] [PubMed] [Google Scholar]
  16. Mercer W. E., Shields M. T., Lin D., Appella E., 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 U S A. 1991 Mar 1;88(5):1958–1962. doi: 10.1073/pnas.88.5.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Milner J. The role of p53 in the normal control of cell proliferation. Curr Opin Cell Biol. 1991 Apr;3(2):282–286. doi: 10.1016/0955-0674(91)90153-p. [DOI] [PubMed] [Google Scholar]
  18. Prosser J., Thompson A. M., Cranston G., Evans H. J. Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. Oncogene. 1990 Oct;5(10):1573–1579. [PubMed] [Google Scholar]
  19. 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]
  20. Quinlan D. C., Davidson A. G., Summers C. L., Warden H. E., Doshi H. M. Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res. 1992 Sep 1;52(17):4828–4831. [PubMed] [Google Scholar]
  21. Takahashi T., Carbone D., Takahashi T., Nau M. M., Hida T., Linnoila I., Ueda R., Minna J. D. Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res. 1992 Apr 15;52(8):2340–2343. [PubMed] [Google Scholar]
  22. Volm M., Efferth T., Mattern J. Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. Anticancer Res. 1992 Jan-Feb;12(1):11–20. [PubMed] [Google Scholar]

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