Her-2 Immunohistochemical Expression in Oral Squamous Cell Carcinomas is Associated with Polysomy of Chromosome 17, Not Her-2 Amplification

Abstract

Based on the prognostic role of Her-2 amplification and protein overexpression in breast cancer, various studies have been performed in oral squamous cell carcinomas (OSCC) with inconsistent results. As in invasive breast carcinomas Her-2 overexpression has been related to an increased number of chromosome 17 copies, a common chromosomal alteration in OSCC, we evaluated the association between polysomy 17 and Her-2 protein expression in a series of primary OSCC. Forty-one incisional biopsies of primary OSCC were included in the study. Protein expression was evaluated immunochistochemically with CB11 mouse monoclonal anti-human antibody. The reaction was arbitrarily characterized as absent, faint, moderate, and strong, and staining pattern as cytoplasmic and membranous. Positive cases were analyzed by chromogenic in situ hybridisation (CISH) to access Her-2 status. The association between polysomy 17 and Her-2 expression was checked by Fisher’s exact test. Four cases were negative and 37 cases were positive for Her-2. Staining was faint in 15 cases and moderate in 22 cases. CISH showed that all cases with faint staining were diploid, while from the cases with moderate staining 10 were diploid and 12 polysomic for chromosome 17. Thirteen cases showed purely cytoplasmic staining, while in 24 there were areas of both cytoplasmic and membranous staining. There was a statistically significant correlation between intensity of the reaction and polysomy 17 (P = 0.0036), in particular for cases with both cytoplasmic and membranous staining (P = 0.0128). In some OSCC Her-2 immunohistochemical expression may be associated with chromosome 17 polysomy and not Her-2 amplification.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Schechter AL, Stern DF, Vaidyanathan L, et al. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984;312:513–6.

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Rubin I, Yarden Y. The basic biology of HER2. Ann Oncol. 2001;12(Suppl 1):S3–8.

    Article  PubMed  Google Scholar 

  3. 3.

    Casalini P, Iorio MV, Galmozzi E, et al. Role of HER receptors family in development and differentiation. J Cell Physiol. 2004;200:343–50.

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    O-Charoenrat P, Rhys-Evans PH, Modjtahedi H, et al. The role of c-erbB receptors and ligands in head and neck squamous cell carcinoma. Oral Oncol. 2002;38:627–40.

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Salido M, Tusquets I, Corominas JM, et al. Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry. Breast Cancer Res. 2005;7:R267–73.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Craven JM, Pavelic ZP, Stambrook PJ, et al. Expression of c-erbB-2 gene in human head and neck carcinoma. Anticancer Res. 1992;12:2273–6.

    CAS  PubMed  Google Scholar 

  7. 7.

    Beckhardt RN, Kiyokawa N, Xi L, et al. HER-2/neu oncogene characterization in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 1995;121:1265–70.

    CAS  PubMed  Google Scholar 

  8. 8.

    Xia W, Lau YK, Zhang HZ, et al. Strong correlation between c-erbB-2 overexpression and overall survival of patients with oral squamous cell carcinoma. Clin Cancer Res. 1997;3:3–9.

    CAS  PubMed  Google Scholar 

  9. 9.

    Ibrahim SO, Vasstrand EN, Liavaag PG, et al. Expression of c-erbB proto-oncogene family members in squamous cell carcinoma of the head and neck. Anticancer Res. 1997;17:4539–46.

    CAS  PubMed  Google Scholar 

  10. 10.

    Xia W, Lau YK, Zhang HZ, et al. Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res. 1999;5:4164–74.

    CAS  PubMed  Google Scholar 

  11. 11.

    Giatromanolaki A, Koukourakis MI, Sivridis E, et al. c-erbB-2 oncoprotein is overexpressed in poorly vascularised squamous cell carcinomas of the head and neck, but is not associated with response to cytotoxic therapy or survival. Anticancer Res. 2000;20:997–1004.

    CAS  PubMed  Google Scholar 

  12. 12.

    Hoffmann TK, Ballo H, Braunstein S, et al. Serum level and tissue expression of c-erbB-1 and c-erbB-2 proto-oncogene products in patients with squamous cell carcinoma of the head and neck. Oral Oncol. 2001;37:50–6.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Khademi B, Shirazi FM, Vasei M, et al. The expression of p53, c-erbB-1 and c-erbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors. Cancer Lett. 2002;184:223–30.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Kuropkat C, Venkatesan TK, Caldarelli DD, et al. Abnormalities of molecular regulators of proliferation and apoptosis in carcinoma of the oral cavity and oropharynx. Auris Nasus Larynx. 2002;29:165–74.

    Article  PubMed  Google Scholar 

  15. 15.

    Khan AJ, King BL, Smith BD, et al. Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2002;8:540–8.

    CAS  PubMed  Google Scholar 

  16. 16.

    Nagler RM, Kerner H, Laufer D, et al. Squamous cell carcinoma of the tongue: the prevalence and prognostic roles of p53, Bcl-2, c-erbB-2 and apoptotic rate as related to clinical and pathological characteristics in a retrospective study. Cancer Lett. 2002;186:137–50.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Scheer M, Prange W, Petmecky K, et al. Evaluation of her-2/neu amplification/overexpression in OSCC with fluorescence in situ hybridization (FISH) and immunohistochemistry. Mund Kiefer Gesichtschir. 2003;7:138–45.

    CAS  PubMed  Google Scholar 

  18. 18.

    Parise Junior O, Carvalho LV, Miguel RE, et al. Prognostic impact of p53, c-erbB-2 and epidermal growth factor receptor on head and neck carcinoma. Sao Paulo Med J. 2004;122:264–8.

    PubMed  Google Scholar 

  19. 19.

    Schartinger VH, Kacani L, Andrle J, et al. Pharmacodiagnostic value of the HER family in head and neck squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2004;66:21–6.

    CAS  PubMed  Google Scholar 

  20. 20.

    Ulanovski D, Stern Y, Roizman P, et al. Expression of EGFR and Cerb-B2 as prognostic factors in cancer of the tongue. Oral Oncol. 2004;40:532–7.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Bei R, Budillon A, Masuelli L, et al. Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. J Pathol. 2004;204:317–25.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Cavalot A, Martone T, Roggero N, et al. Prognostic impact of HER-2/neu expression on squamous head and neck carcinomas. Head Neck. 2007;29:655–64.

    Article  PubMed  Google Scholar 

  23. 23.

    Rautava J, Jee KJ, Miettinen PJ, et al. ERBB receptors in developing, dysplastic and malignant oral epithelia. Oral Oncol. 2008;44:227–35.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Angiero F, Sordo RD, Dessy E, et al. Comparative analysis of c-erbB-2 (HER-2/neu) in squamous cell carcinoma of the tongue: does over-expression exist? And what is its correlation with traditional diagnostic parameters? J Oral Pathol Med. 2008;37:145–50.

    PubMed  Google Scholar 

  25. 25.

    Nunes CB, Rocha RM, Reis-Filho JS, et al. Comparative analysis of six different antibodies against Her2 including the novel rabbit monoclonal antibody (SP3) and chromogenic in situ hybridisation in breast carcinomas. J Clin Pathol. 2008;61:934–8.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Varshney D, Zhou YY, Geller SA, et al. Determination of HER-2 status and chromosome 17 polysomy in breast carcinomas comparing HercepTest and PathVysion FISH assay. Am J Clin Pathol. 2004;121:70–7.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Ekberg T, Nestor M, Engstrom M, et al. Expression of EGFR, HER2, HER3, and HER4 in metastatic squamous cell carcinomas of the oral cavity and base of tongue. Int J Oncol. 2005;26:1177–85.

    CAS  PubMed  Google Scholar 

  28. 28.

    Albuquerque RL Jr, Miguel MC, Costa AL, et al. Correlation of c-erbB-2 and S-100 expression with the malignancy grading and anatomical site in oral squamous cell carcinoma. Int J Exp Pathol. 2003;84:259–65.

    Article  PubMed  Google Scholar 

  29. 29.

    Do NY, Lim SC, Im TS. Expression of c-erbB receptors, MMPs and VEGF in squamous cell carcinoma of the head and neck. Oncol Rep. 2004;12:229–37.

    CAS  PubMed  Google Scholar 

  30. 30.

    Kilpi A, Rich AM, Konttinen YT, et al. The expression of c-erbB-2 protein in the keratinocytes of oral mucosal lichen planus. Br J Dermatol. 1995;133:847–52.

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Kilpi A, Rich AM, Konttinen YT, et al. Expression of c-erbB-2 protein in keratinocytes of oral mucosal lichen planus and subsequent squamous cell carcinoma. Eur J Oral Sci. 1996;104:278–84.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Wilkman TS, Hietanen JH, Malmstrom MJ, et al. Immunohistochemical analysis of the oncoprotein c-erbB-2 expression in oral benign and malignant lesions. Int J Oral Maxillofac Surg. 1998;27:209–12.

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Hou L, Shi D, Tu SM, et al. Oral cancer progression and c-erbB-2/neu proto-oncogene expression. Cancer Lett. 1992;65:215–20.

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Freier K, Bosch FX, Flechtenmacher C, et al. Distinct site-specific oncoprotein overexpression in head and neck squamous cell carcinoma: a tissue microarray analysis. Anticancer Res. 2003;23:3971–7.

    CAS  PubMed  Google Scholar 

  35. 35.

    Rodrigo JP, Ramos S, Lazo PS, et al. Amplification of ERBB oncogenes in squamous cell carcinomas of the head and neck. Eur J Cancer. 1996;32A:2004–10.

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Leonard JH, Kearsley JH, Chenevix-Trench G, et al. Analysis of gene amplification in head-and-neck squamous cell carcinoma. Int J Cancer. 1991;48:511–5.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Willmore-Payne C, Holden JA, Layfield LJ. Detection of EGFR- and HER2-activating mutations in squamous cell carcinoma involving the head and neck. Mod Pathol. 2006;19:634–40.

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    O-Charoenrat P, Rhys-Evans P, Eccles S. Characterization of ten newly-derived human head and neck squamous carcinoma cell lines with special reference to c-erbB proto-oncogene expression. Anticancer Res. 2001;21:1953–63.

    CAS  PubMed  Google Scholar 

  39. 39.

    Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Rashid-Kolvear F, Pintilie M, Done SJ. Telomere length on chromosome 17q shortens more than global telomere length in the development of breast cancer. Neoplasia. 2007;9:265–70.

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Hyun CL, Lee HE, Kim KS, et al. The effect of chromosome 17 polysomy on HER-2/neu status in breast cancer. J Clin Pathol. 2008;61:317–21.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Lal P, Salazar PA, Ladanyi M, et al. Impact of polysomy 17 on HER-2/neu immunohistochemistry in breast carcinomas without HER-2/neu gene amplification. J Mol Diagn. 2003;5:155–9.

    CAS  PubMed  Google Scholar 

  43. 43.

    Kanekawa A, Tsuji T, Oga A, et al. Chromosome 17 abnormalities in squamous cell carcinoma of the oral cavity, and its relationship with p53 and Bcl-2 expression. Anticancer Res. 1999;19:81–6.

    CAS  PubMed  Google Scholar 

  44. 44.

    Voravud N, Shin DM, Ro JY, et al. Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res. 1993;53:2874–83.

    CAS  PubMed  Google Scholar 

  45. 45.

    Field JK, Spandidos DA, Yiagnisis M, et al. C-erbB-2 expression in squamous cell carcinoma of the head and neck. Anticancer Res. 1992;12:613–9.

    CAS  PubMed  Google Scholar 

  46. 46.

    Kearsley JH, Leonard JH, Walsh MD, et al. A comparison of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene expression in head and neck squamous cell carcinomas. Pathology. 1991;23:189–94.

    Article  CAS  PubMed  Google Scholar 

  47. 47.

    Press MF, Hung G, Godolphin W, et al. Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression. Cancer Res. 1994;54:2771–7.

    CAS  PubMed  Google Scholar 

  48. 48.

    Weinstein GS, Nuamah IF, Tucker J, et al. Evaluation of HER-2/neu (c-erbB-2) oncogene expression in whole organ sections of supraglottic squamous cell carcinoma. Ann Otol Rhinol Laryngol. 1996;105:275–9.

    CAS  PubMed  Google Scholar 

  49. 49.

    Saez A, Andreu FJ, Segui MA, et al. HER-2 gene amplification by chromogenic in situ hybridisation (CISH) compared with fluorescence in situ hybridisation (FISH) in breast cancer-A study of two hundred cases. Breast. 2006;15:519–27.

    Article  CAS  PubMed  Google Scholar 

  50. 50.

    Hanna WM, Kwok K. Chromogenic in situ hybridization: a viable alternative to fluorescence in situ hybridization in the HER2 testing algorithm. Mod Pathol. 2006;19:481–7.

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Bilous M, Morey A, Armes J, et al. Chromogenic in situ hybridisation testing for HER2 gene amplification in breast cancer produces highly reproducible results concordant with fluorescence in situ hybridisation and immunohistochemistry. Pathology. 2006;38:120–4.

    Article  CAS  PubMed  Google Scholar 

  52. 52.

    Sauer T, Wiedswang G, Boudjema G, et al. Assessment of HER-2/neu overexpression and/or gene amplification in breast carcinomas: should in situ hybridization be the method of choice? APMIS. 2003;111:444–50.

    Article  CAS  PubMed  Google Scholar 

  53. 53.

    O-Charoenrat P, Rhys-Evans P, Eccles S. Characterization of ten newly-derived human head and neck squamous carcinoma cell lines with special reference to c-erbB proto-oncogene expression. Anticancer Res. 2001;21:1953–63.

    CAS  PubMed  Google Scholar 

  54. 54.

    Freier K, Joos S, Flechtenmacher C, et al. Tissue microarray analysis reveals site-specific prevalence of oncogene amplifications in head and neck squamous cell carcinoma. Cancer Res. 2003;63:1179–82.

    CAS  PubMed  Google Scholar 

  55. 55.

    Bose S, Mohammed M, Shintaku P, et al. Her-2/neu gene amplification in low to moderately expressing breast cancers: possible role of chromosome 17/Her-2/neu polysomy. Breast J. 2001;7:337–44.

    Article  CAS  PubMed  Google Scholar 

  56. 56.

    Charuruks N, Shin DM, Voravud N, et al. Genetic instabilities of chromosome 9, 17 and accumulation of p53 overexpression during multistage tumorigesis in head and neck cancer. J Med Assoc Thai. 1996;79(Suppl 1):S104–12.

    PubMed  Google Scholar 

  57. 57.

    Shin DM, Charuruks N, Lippman SM, et al. p53 protein accumulation and genomic instability in head and neck multistep tumorigenesis. Cancer Epidemiol Biomarkers Prev. 2001;10:603–9.

    CAS  PubMed  Google Scholar 

  58. 58.

    Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18–43.

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Konstantinos Tosios.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Papavasileiou, D., Tosios, K., Christopoulos, P. et al. Her-2 Immunohistochemical Expression in Oral Squamous Cell Carcinomas is Associated with Polysomy of Chromosome 17, Not Her-2 Amplification. Head and Neck Pathol 3, 263 (2009). https://doi.org/10.1007/s12105-009-0134-1

Download citation

Keywords

  • Her-2 Gene
  • Genetic abnormalities
  • Oral squamous cell carcinoma
  • Immunohistochemistry
  • Hybridization in situ