Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jun;69(6):995–999. doi: 10.1038/bjc.1994.195

Expression of ras oncogene p21 protein in normal and neoplastic laryngeal tissues: correlation with histopathological features and epidermal growth factor receptors.

G Scambia 1, L Catozzi 1, P Benedetti Panici 1, G Ferrandina 1, G Almadori 1, G Paludetti 1, G Cadoni 1, M Distefano 1, A Piffanelli 1, S Mancuso 1, et al.
PMCID: PMC1969458  PMID: 8198992

Abstract

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer.

Full text

PDF
998

Images in this article

Selected References

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

  1. Anderson J. A., Irish J. C., Ngan B. Y. Prevalence of RAS oncogene mutation in head and neck carcinomas. J Otolaryngol. 1992 Oct;21(5):321–326. [PubMed] [Google Scholar]
  2. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  3. Battaglia F., Scambia G., Rossi S., Panici P. B., Bellantone R., Polizzi G., Querzoli P., Negrini R., Iacobelli S., Crucitti F. Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement. Eur J Cancer Clin Oncol. 1988 Nov;24(11):1685–1690. doi: 10.1016/0277-5379(88)90068-5. [DOI] [PubMed] [Google Scholar]
  4. Boltz E. M., Kefford R. F., Leary J. A., Houghton C. R., Friedlander M. L. Amplification of c-ras-Ki oncogene in human ovarian tumours. Int J Cancer. 1989 Mar 15;43(3):428–430. doi: 10.1002/ijc.2910430314. [DOI] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. Carpenter G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu Rev Biochem. 1987;56:881–914. doi: 10.1146/annurev.bi.56.070187.004313. [DOI] [PubMed] [Google Scholar]
  7. Clair T., Miller W. R., Cho-Chung Y. S. Prognostic significance of the expression of a ras protein with a molecular weight of 21,000 by human breast cancer. Cancer Res. 1987 Oct 15;47(20):5290–5293. [PubMed] [Google Scholar]
  8. DeBortoli M. E., Abou-Issa H., Haley B. E., Cho-Chung Y. S. Amplified expression of p21 ras protein in hormone-dependent mammary carcinomas of humans and rodents. Biochem Biophys Res Commun. 1985 Mar 15;127(2):699–706. doi: 10.1016/s0006-291x(85)80218-7. [DOI] [PubMed] [Google Scholar]
  9. Furth M. E., Davis L. J., Fleurdelys B., Scolnick E. M. Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol. 1982 Jul;43(1):294–304. doi: 10.1128/jvi.43.1.294-304.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gallick G. E., Kurzrock R., Kloetzer W. S., Arlinghaus R. B., Gutterman J. U. Expression of p21ras in fresh primary and metastatic human colorectal tumors. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1795–1799. doi: 10.1073/pnas.82.6.1795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
  12. Hughes D. A., Fukui Y., Yamamoto M. Homologous activators of ras in fission and budding yeast. Nature. 1990 Mar 22;344(6264):355–357. doi: 10.1038/344355a0. [DOI] [PubMed] [Google Scholar]
  13. Irish J. C. Oncogenes, molecular biology and the head and neck surgeon. J Otolaryngol. 1992 Dec;21 (Suppl 3):1–20. [PubMed] [Google Scholar]
  14. Kurzrock R., Gallick G. E., Gutterman J. U. Differential expression of p21ras gene products among histological subtypes of fresh primary human lung tumors. Cancer Res. 1986 Mar;46(3):1530–1534. [PubMed] [Google Scholar]
  15. Long C. A., O'Brien T. J., Sanders M. M., Bard D. S., Quirk J. G., Jr ras oncogene is expressed in adenocarcinoma of the endometrium. Am J Obstet Gynecol. 1988 Dec;159(6):1512–1516. doi: 10.1016/0002-9378(88)90586-8. [DOI] [PubMed] [Google Scholar]
  16. Maurizi M., Scambia G., Benedetti Panici P., Ferrandina G., Almadori G., Paludetti G., De Vincenzo R., Distefano M., Brinchi D., Cadoni G. EGF receptor expression in primary laryngeal cancer: correlation with clinico-pathological features and prognostic significance. Int J Cancer. 1992 Dec 2;52(6):862–866. doi: 10.1002/ijc.2910520605. [DOI] [PubMed] [Google Scholar]
  17. McGrath J. P., Capon D. J., Goeddel D. V., Levinson A. D. Comparative biochemical properties of normal and activated human ras p21 protein. Nature. 1984 Aug 23;310(5979):644–649. doi: 10.1038/310644a0. [DOI] [PubMed] [Google Scholar]
  18. Merritt W. D., Weissler M. C., Turk B. F., Gilmer T. M. Oncogene amplification in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 1990 Dec;116(12):1394–1398. doi: 10.1001/archotol.1990.01870120040005. [DOI] [PubMed] [Google Scholar]
  19. Rodenburg C. J., Koelma I. A., Nap M., Fleuren G. J. Immunohistochemical detection of the ras oncogene product p21 in advanced ovarian cancer. Lack of correlation with clinical outcome. Arch Pathol Lab Med. 1988 Feb;112(2):151–154. [PubMed] [Google Scholar]
  20. Satoh M., Hatakeyama S., Sashima M., Suzuki A. Immunohistochemical detection of ras 21 in oral squamous cell carcinomas. Oral Surg Oral Med Oral Pathol. 1992 Oct;74(4):469–472. doi: 10.1016/0030-4220(92)90298-5. [DOI] [PubMed] [Google Scholar]
  21. Satoh T., Endo M., Nakafuku M., Akiyama T., Yamamoto T., Kaziro Y. Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7926–7929. doi: 10.1073/pnas.87.20.7926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Scambia G., Catozzi L., Benedetti-Panici P., Ferrandina G., Battaglia F., Giovannini G., Distefano M., Pellizzola D., Piffanelli A., Mancuso S. Expression of ras p21 oncoprotein in normal and neoplastic human endometrium. Gynecol Oncol. 1993 Sep;50(3):339–346. doi: 10.1006/gyno.1993.1222. [DOI] [PubMed] [Google Scholar]
  23. Scambia G., Catozzi L., Panici P. B., Ferrandina G., Coronetta F., Barozzi R., Baiocchi G., Uccelli L., Piffanelli A., Mancuso S. Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor. Am J Obstet Gynecol. 1993 Jan;168(1 Pt 1):71–78. doi: 10.1016/s0002-9378(12)90888-1. [DOI] [PubMed] [Google Scholar]
  24. Sheng Z. M., Barrois M., Klijanienko J., Micheau C., Richard J. M., Riou G. Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas. Br J Cancer. 1990 Sep;62(3):398–404. doi: 10.1038/bjc.1990.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Smit V. T., Boot A. J., Smits A. M., Fleuren G. J., Cornelisse C. J., Bos J. L. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 1988 Aug 25;16(16):7773–7782. doi: 10.1093/nar/16.16.7773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Spandidos D. A., Kerr I. B. Elevated expression of the human ras oncogene family in premalignant and malignant tumours of the colorectum. Br J Cancer. 1984 Jun;49(6):681–688. doi: 10.1038/bjc.1984.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spandidos D. A. Oncogene activation in malignant transformation: a study of H-ras in human breast cancer. Anticancer Res. 1987 Sep-Oct;7(5B):991–996. [PubMed] [Google Scholar]
  28. Tanaka T., Slamon D. J., Battifora H., Cline M. J. Expression of p21 ras oncoproteins in human cancers. Cancer Res. 1986 Mar;46(3):1465–1470. [PubMed] [Google Scholar]
  29. Viola M. V., Fromowitz F., Oravez S., Deb S., Schlom J. ras Oncogene p21 expression is increased in premalignant lesions and high grade bladder carcinoma. J Exp Med. 1985 May 1;161(5):1213–1218. doi: 10.1084/jem.161.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  31. Walker R. A., Wilkinson N. p21 ras protein expression in benign and malignant human breast. J Pathol. 1988 Oct;156(2):147–153. doi: 10.1002/path.1711560209. [DOI] [PubMed] [Google Scholar]
  32. van 't Veer L. J., Hermens R., van den Berg-Bakker L. A., Cheng N. C., Fleuren G. J., Bos J. L., Cleton F. J., Schrier P. I. ras oncogene activation in human ovarian carcinoma. Oncogene. 1988 Feb;2(2):157–165. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES