Skip to main content
Log in

Coexpression of p53 and c-erbB-2 proteins is associated with histological type, tumour stage, and cell proliferation in malignant salivary gland tumours

  • Original Articles
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The development and progression of cancer are known to be regulated by various oncogenes and tumour suppressor genes. We analysed 63 primary malignant salivary gland tumours for the expression of p53 and c-erbB-2 proteins. Immunohistochemically, 7 of 63 tumours (11%) showed diffuse nuclear staining for p53 protein, and all 7 were also positive for c-erbB-2 protein. The overexpression of p53 protein correlated closely with the overexpression of c-erbB-2 protein (P<0.001). Overexpression of both p53 and c-erbB-2 proteins (coexpression) was found in tumours of certain histological types, such as adenocarcinoma, carcinoma in pleomorphic adenoma, and salivary duct carcinoma. Furthermore, it is noteworthy that coexpression was associated with high-grade carcinoma, advanced tumour stage, and a high Ki-67 labelling index (%) which is a marker of cell proliferation. In adenocarcinoma, we attempted to clarify the relationship between coexpression and histological grade. Coexpression was associated with histological grades showing high mitotic indices and necrotic areas, which reflected high cell-proliferative activity. These results suggest that the accumulation of genetic alterations, such as those involving p53 and c-erbB-2, plays an important part in the progression of malignant salivary gland tumours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Azuma M, Kasai Y, Tamatani T, Sato M (1992) Involvement of p53 mutation in the development of human salivary gland pleomorphic adenomas. Cancer Lett 65:61–71

    Google Scholar 

  2. Baas IO, Mulder JR, Offerhaus GJA, Vogelstein B, Hamilton SR (1994) An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasmas. J Pathol (Lond) 172:5–12

    Google Scholar 

  3. Barbareschi M, Leonardi E, Mauri FA, et al (1992) p53 and c-erbB-2 protein expression in breast carcinomas: an immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer. Am J Clin Pathol 98:408–418

    Google Scholar 

  4. Barnes DM, Dublin EA, Fisher CJ, et al (1993) Immunohistochemical detection of p53 protein in mammary carcinoma: an important new independent indicator of prognosis. Hum Pathol 24:469–476

    Google Scholar 

  5. Brambilla E, Gazzeri S, Mor D, et al (1993) Immunohistochemical study of p53 in human lung carcinomas. Am J Pathol 143:199–210

    Google Scholar 

  6. Cattoretti G, Rilke F, Andoreola S, et al (1988) p53 expression in breast cancer. Int J Cancer 41:178–183

    Google Scholar 

  7. Deguchi H, Hamano H, Hayashi Y (1993) c-myc, ras p21, and p53 expression in pleomorphic adenoma and its malignant form of the human salivary glands. Acta Pathol Jpn 43:413–422

    Google Scholar 

  8. Delahunt B, Bethwaite PB, Thornton A, Ribas JL (1995) Proliferation of renal cell carcinoma assessed by fixation-resistant polyclonal Ki-67 antibody labeling. Cancer 75:2714–2719

    Google Scholar 

  9. Ellis GL, Auclair PL (1991) Classification of salivary gland neoplasms. In: Ellis GL, Auclair PL, Guepp DR (eds) Surgical pathology of the salivary glands. Saunders, Philadelphia, pp 318–332

    Google Scholar 

  10. Fearon ER, Volgelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Google Scholar 

  11. Haerslev T, Jacobsen GK (1995) An immunohistochemical study of p53 with correlations to histopathological parameters, c-erbB-2, proliferating cell nuclear antigen, and prognosis. Hum Pathol 26:295–301

    Google Scholar 

  12. Hurlimann J, Saraga EP (1994) Expression of p53 protein in gastric carcinomas. Am J Surg Pathol 18:1247–1253

    Google Scholar 

  13. Ishii K, Nakajima T (1994) Evaluation of malignant grade of salivary gland tumors: studies by cytofluorometric nuclear DNA analysis, histochemistry for nucleolar organizer regions and immunohistochemistry for p53. Pathol Int 44:287–296

    Google Scholar 

  14. Isola J, Visakorpi T, Holli K, Kallioniemi O-P (1992) Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-positive breast cancer patients. J Natl Cancer Inst 84:1109–1114

    Google Scholar 

  15. Kernohan NM, Blessing K, King G, Corbett IP, Miller ID (1991) Expression of c-erbB-2 oncoprotein in salivary gland tumors: an immunohistochemical study. J Pathol (Lond) 163:81–85

    Google Scholar 

  16. Martin HM, Filipe MI, Morris RW, et al (1992) p53 Expression and prognosis in gastric carcinoma. Int J Cancer 50:859–862

    Google Scholar 

  17. Midgley CA, Fisher CJ, Bartek J, Vojtesek B, Lane D, Barenes DM (1992) Analysis of p53 expression in human tumors: an antibody raised against human p53 expressed in Escherichia coli. J Cell Sci 101:183–189

    Google Scholar 

  18. Murakami M, Ohtani I, Hojo H, Wakasa H (1992) Immunohistochemical evaluation with Ki-67: an application to salivary gland tumours. J Laryngol Otol 106:35–38

    Google Scholar 

  19. Nagao T, Kondo F, Sato T, Nagato Y, Kondo Y (1995) Immunohistochemical detection of aberrant p53 expression in hepatocelluar carcinoma. Hum Pathol 26:326–333

    Google Scholar 

  20. Press MF, Pike MC, Hung G, Zhou JY, Ma Y, George J, Dietz-Band J, James W, Slamon JG, Batsakis JG, El-Naggar AK (1994) Amplication and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis. Cancer Res 54:5675–5682

    Google Scholar 

  21. Sasano H, Miyazaki S, Gooukon Y, et al (1992) Expression of p53 in human esophageal carcinoma: an immunohistochemical study with correlation to proliferating cell nuclear antigen expression. Hum Pathol 23:1238–1243

    Google Scholar 

  22. Seifert G (1991) Histological typing of salivary gland tumours. (World Health Organization) Springer, Berlin Heidelberg New York

    Google Scholar 

  23. Shrestha P, Huang JW, Tsuji T, Shinozaki F, Maeda K, Sasaki K, Ueno K, Yamada K, Mori M (1992) Rare expression of the c-erbB-2 oncoprotein in salivary gland tumors: immunohistochemical study. J Oral Pathol Med 21:477–480

    CAS  PubMed  Google Scholar 

  24. Slamon DJ, Godolphin W, Jones LA, et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712

    CAS  PubMed  Google Scholar 

  25. Spiro RH, Huvos AG, Strong EW (1982) Adenocarcinoma of salivary gland origin: clinicopathologic study of 204 patients. Am J Surg 144:423–431

    Google Scholar 

  26. Sugano S, Mukai K, Tsuda H, Hirohashi S, Furuya S, Shimosato Y, Ebihara S, Takeyama I (1992) Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. Laryngoscope 102:923–927

    Google Scholar 

  27. Thackray AC, Lucas RB (1974) Tumors of the major salivary glands. Armed Forces Institute of Pathology, Washington, DC

    Google Scholar 

  28. Van den Berg FM, Tigges AJ, Schipper MEI, et al (1989) Expression of the nuclear oncogene p53 in colon tumours. J Pathol (Lond) 157:193–199

    Google Scholar 

  29. Wiltschke C, Kindas-Mueggen I, Steininger A, Reiner A, Reiner G, Preis PN (1994) Coexpression of HER-2/neu and p53 is associated with a shorter disease-free survival in node-positive breast cancer patients. J Cancer Res Clin Oncol 120:737–742

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamio, N. Coexpression of p53 and c-erbB-2 proteins is associated with histological type, tumour stage, and cell proliferation in malignant salivary gland tumours. Vichows Archiv A Pathol Anat 428, 75–83 (1996). https://doi.org/10.1007/BF00193934

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00193934

Key words

Navigation