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BCL-2, p53 and HLA-DR antigen expression in surgically treated parotid cancer patients

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Abstract

Our objective was to investigate the prognostic significance of bcl-2 protein, p53 protein and HLA-DR antigen expression in a group of surgically treated parotid cancer patients. We studied bcl-2, p53 and HLA-DR immunohistochemical expression in paraffin-embedded surgically removed tissue specimens derived from 26 patients with parotid cancer and 9 patients with Warthin parotid tumors operated between 2000 and 2006 at the Hippokration Hospital of Athens. The staining results were correlated with the patients’ clinicopathological characteristics and clinical outcome. Bcl-2 expression was associated with a significantly decreased survival in patients with advanced tumor stage (P = 0.04), high grade lesions (P = 0.02), or cervical node involvement (P = 0.03). Radiotherapy was associated with a significantly improved recurrence-free survival among patients with negative tumor staining for either bcl-2, or both HLA-DR and bcl-2 [HLA-DR(−)/Bcl-2(−)] (P = 0.04 for both comparisons). Classical clinicopathologic factors failed to show prognostic value both in the univariate and the multivariate analyses performed. Our results suggest that bcl-2 can be used to identify locally advanced or histologically aggressive tumors with a lower survival probability following the application of standard treatment modalities. Furthermore, bcl-2(+) patients should be considered for more aggressive adjuvant treatment protocols, since conventional radiotherapy often fails to decrease relapse rates in this setting of patients.

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References

  1. Nagler RM, Kerner H, Ben-Eliezer S, Minkov I, Ben-Itzhak O (2003) Prognostic role of apoptotic, Bcl-2, c-erbB-2 and p53 tumor markers in salivary gland malignancies. Oncology 64:389–398

    Article  PubMed  CAS  Google Scholar 

  2. Cadwell C, Zambetti GP (2001) The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth. Gene 277:15–30

    Article  PubMed  CAS  Google Scholar 

  3. Gallo O, Franchi A, Bianchi S, Boddi V, Giannelli E, Alajmo E (1995) P53 oncoprotein expression in parotid gland carcinoma is associated with clinical outcome. Cancer 75:2037–2044

    Article  PubMed  CAS  Google Scholar 

  4. Benacerraf B (1981) Role of MHC gene products in immune regulation. Science 212:1229–1238

    Article  PubMed  CAS  Google Scholar 

  5. Kaufman JF, Auffray C, Korman AJ, Shackelford DA, Strominger J (1984) The class II molecules of the human and murine major histocompatibility complex. Cell 36:1–13

    Article  PubMed  CAS  Google Scholar 

  6. Ghosh AK, Moore M, Street AJ, Howat JM, Schofield PF (1986) Expression of HLA-D sub-region products on human colorectal carcinoma. Int J Cancer 38:459–464

    Article  PubMed  CAS  Google Scholar 

  7. Festenstein H (1987) The biological consequences of altered MHC expression on tumours. Br Med Bull 43:217–227

    PubMed  CAS  Google Scholar 

  8. Barnes L, Eveson JW, Reichart P, Sidfransky D (2005) World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. IARC Press, Lyons, pp 209–281

    Google Scholar 

  9. American Joint Committee on Cancer. Major salivary glands (parotid, submandibular, and sublingual) (2002) In: AJCC Cancer Staging Manual, 6th edn. Springer, New York, pp 53–58

  10. Darom A, Gomatos IP, Leandros E, Xatziyiannis E, Fotiadis C, Konstadoulakis MM (2004) HLA-DR antigen and bax protein expression in patients with primary non-Hodgkin’s gastric lymphoma. Hybrid Hybridomics 23:87–92

    Article  PubMed  CAS  Google Scholar 

  11. Tullio A, Marchetti C, Sesenna E, Brusati R, Cocchi R, Eusebi V (2001) Treatment of carcinoma of the parotid gland: the results of a multicenter study. J Oral Maxillofac Surg 59:263–270

    Article  PubMed  CAS  Google Scholar 

  12. Renehan AG, Gleave EN, Slevin NJ, McGurk M (1999) Clinico-pathological and treatment-related factors influencing survival in parotid cancer. Br J Cancer 80:1296–1300

    Article  PubMed  CAS  Google Scholar 

  13. Georgiou A, Gomatos IP, Ferekidis E, Syrigos K, Bistola V, Giotakis J, Adamopoulos G, Androulakis G (2001) Prognostic significance of p53, bax and bcl-2 gene expression in patients with laryngeal carcinoma. Eur J Surg Oncol 27:574–580

    Article  PubMed  CAS  Google Scholar 

  14. Cadwell C, Zambetti GP (2001) The effects of wild-type p53 tumor suppressor activity and mutant p53 gain-of-function on cell growth. Gene 277:15–30

    Article  PubMed  CAS  Google Scholar 

  15. Baas IO, Mulder JW, Offerhaus GJ, Vogelstein B, Hamilton SR (1994) An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 172:5–12

    Article  PubMed  CAS  Google Scholar 

  16. Nagao T, Sugano I, Ishida Y, Hasegawa M, Matsuzaki O, Konno A, Kondo Y, Nagao K (1998) Basal cell adenocarcinoma of the salivary glands: comparison with basal cell adenoma through assessment of cell proliferation, apoptosis, and expression of p53 and bcl-2. Cancer 82:439–447

    Article  PubMed  CAS  Google Scholar 

  17. Haldar S, Chintapalli J, Croce CM (1996) Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 56:1253–1255

    PubMed  CAS  Google Scholar 

  18. Ravi D, Nalinakumari KR, Rajaram RS, Nair MK, Pillai MR (1996) Expression of programmed cell death regulatory p53 and bcl-2 proteins in oral lesions. Cancer Lett 105:139–146

    Article  PubMed  CAS  Google Scholar 

  19. Jordan RC, Catzavelos GC, Barrett AW, Speight PM (1996) Differential expression of bcl-2 and bax in squamous cell carcinomas of the oral cavity. Eur J Cancer B Oral Oncol 32:394–400

    Article  Google Scholar 

  20. Garrido F (1991) MHC molecules in normal and neoplastic cells. Int J Cancer Suppl 6:1

    Article  Google Scholar 

  21. Zaloudik J, Moore M, Ghosh AK, Mechl Z, Rejthar A (1988) DNA content and MHC class II antigen expression in malignant melanoma: clinical course. J Clin Pathol 41:1078–1084

    Article  PubMed  CAS  Google Scholar 

  22. Konstadoulakis MM, Vezeridis M, Cannizzo F, Golematis BC, Bland KI, Wanebo HJ (1995) Prognostic significance of HLA-DR antigen on human breast cancer cells and surrounding breast tissue. American College Surg Surgical Forum 46:536–538

    Google Scholar 

  23. Soini Y, Tormanen U, Paakko P (1998) Apoptosis is inversely related to bcl-2 but not to bax expression in salivary gland tumours. Histopathology 32:28–34

    Article  PubMed  CAS  Google Scholar 

  24. Pollack A, Cowen D, Troncoso P, Zagars GK, von Eschenbach AC, Meistrich ML, McDonnell T (2003) Molecular markers of outcome after radiotherapy in patients with prostate carcinoma: Ki-67, bcl-2, bax, and bcl-x. Cancer 97:1630–1638

    Article  PubMed  Google Scholar 

  25. Rakozy C, Grignon DJ, Sarkar FH, Sakr WA, Littrup P, Forman J (1998) Expression of bcl-2, p53, and p21 in benign and malignant prostatic tissue before and after radiation therapy. Mod Pathol 11:892–899

    PubMed  CAS  Google Scholar 

  26. Allal AS, Waelchli L, Brundler MA (2003) Prognostic value of apoptosis-regulating protein expression in anal squamous cell carcinoma. Clin Cancer Res 9:6489–6496

    PubMed  CAS  Google Scholar 

  27. Jayasurya A, Dheen ST, Yap WM, Tan NG, Ng YK, Bay BH (2003) Inducible nitric oxide synthase, bcl-2 expression in nasopharyngeal cancer: correlation with outcome of patients after radiotherapy. Int J Radiat Oncol Biol Phys 56:837–845

    PubMed  CAS  Google Scholar 

  28. Sohn SK, Jung JT, Kim DH, Kim JG, Kwak EK, Park T, Shin DG, Sohn KR, Lee KB (2003) Prognostic significance of bcl-2, bax, and p53 expression in diffuse large B-cell lymphoma. Am J Hematol 73:101–107

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ilias P. Gomatos.

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Genetzakis, M., Gomatos, I.P., Georgiou, A.N. et al. BCL-2, p53 and HLA-DR antigen expression in surgically treated parotid cancer patients. Eur Arch Otorhinolaryngol 266, 417–424 (2009). https://doi.org/10.1007/s00405-008-0754-1

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  • DOI: https://doi.org/10.1007/s00405-008-0754-1

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