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The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma

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Abstract

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in patients affected by laryngeal squamous cell carcinoma. A systematic review was carried out in a tertiary university referral center. An appropriate string was run on PubMed to retrieve articles dealing with Ki-67 immunohistochemical staining and laryngeal squamous cell carcinoma. A double cross-check was performed on citations and full-text articles by two investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 85 abstracts identified, 18 articles were included. These studies reported on 1,342 patients with histological confirmed diagnosis of laryngeal squamous cell carcinoma. Most studies showed a statistical association between Ki-67 immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. Overall the studies analyzed suggested that the tumoral proliferative index was statistically connected respectively with T stage (2/18), N stage (4/18), grading (6/18), disease-free survival (10/18) and overall survival (4/18). Our review strongly suggests that immunohistochemical staining of Ki-67 correlates with tumoral aggressiveness and worse prognosis in patients affected by laryngeal squamous cell carcinoma. Further high-quality prospective studies should be carried out to confirm our finding and determine the eventual differences between cancers of specific laryngeal subsites.

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References

  1. Ozdek A, Sarac S, Akyol MU, Sungur A, Yilmaz T (2004) c-myc and bcl-2 expression in supraglottic squamous cell carcinoma of the larynx. Otolaryngol Head Neck Surg 131(1):77–83

    Article  PubMed  Google Scholar 

  2. Dequanter D, Lothaire P (2008) The role of salvage surgery in organ preservation strategies in advanced head and neck cancer. B-ENT 4(2):77–80

    CAS  PubMed  Google Scholar 

  3. León X, López M, García J, Viza I, Orús C, Quer M (2007) Supracricoid laryngectomy as salvage surgery after failure of radiation therapy. Eur Arch Otorhinolaryngol 264(7):809–814

    Article  PubMed  Google Scholar 

  4. Theegarten D, Barfuss A, Gellrich NC, Philippou S (2007) Expression of proliferation markers PCNA and MIB 1 in verrucous squamous epithelial carcinoma of the oral cavity. Mund Kiefer Gesichtschir 1(3):133–136

    Google Scholar 

  5. Patel SG, Shah JP (2007) TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA Cancer J Clin 55(4):242–258

    Article  Google Scholar 

  6. Cordes C, Münzel AK, Rudolph P, Hoffmann M, Leuschner I, Gottschlich S (2009) Immunohistochemical staining of Ki-67 using the monoclonal antibody Ki-s11 is a prognostic indicator for laryngeal squamous cell carcinoma. Anticancer Res 29(4):1459–1465

    PubMed  Google Scholar 

  7. Acikalin MF, Oner U, Tel N, Paşaoğlu O, Cakli H, Colak E (2009) Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy. Eur Arch Otorhinolaryngol 261(7):376–380

    Article  Google Scholar 

  8. Mielcarek-Kuchta D, Olofsson J, Golusinski W (2009) p53, Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma. Eur Arch Otorhinolaryngol 260(10):549–554

    Article  Google Scholar 

  9. Pastuszewski W, Dziegiel P, Krecicki T et al (2009) Prognostic significance of metallothionein, p53 protein and Ki-67 antigen expression in laryngeal cancer. Anticancer Res 27(1A):335–342

    Google Scholar 

  10. Kreipe H, Heidebrecht HJ, Hansen S et al (2009) A new proliferation-associated nuclear antigen detectable in paraffin-embedded tissues by the monoclonal antibody Ki-S1. Am J Pathol 142(1):3–9

    Google Scholar 

  11. Pich A, Chiusa L, Navone R (2004) Prognostic relevance of cell proliferation in head and neck tumors. Ann Oncol 15(9):1319–1329

    Article  CAS  PubMed  Google Scholar 

  12. Leong AS, Sormunen RT, Vinyuvat S, Hamdani RW, Suthipintawong C (2001) Biologic markers in ductal carcinoma in situ and concurrent infiltrating carcinoma. A comparison of eight contemporary grading systems. Am J Clin Pathol 115(5):709–718

    Article  CAS  PubMed  Google Scholar 

  13. DeRienzo DP, Greenberg SD, Fraire AE (1991) Carcinoma of the larynx. Changing incidence in women. Arch Otolaryngol Head Neck Surg 117(6):681–684

    Article  CAS  PubMed  Google Scholar 

  14. Ambrosch P (2007) The role of laser microsurgery in the treatment of laryngeal cancer. Curr Opin Otolaryngol Head Neck Surg 15(2):82–88

    Article  PubMed  Google Scholar 

  15. Jones AS, Roland NJ, Caslin AW, Cooke TG, Cooke LD, Forster G (1994) A comparison of cellular proliferation markers in squamous cell carcinoma of the head and neck. J Laryngol Otol 108(10):859–864

    Article  CAS  PubMed  Google Scholar 

  16. Roland NJ, Caslin AW, Bowie GL, Jones AS (1994) Has the cellular proliferation marker Ki67 any clinical relevance in squamous cell carcinoma of the head and neck? Clin Otolaryngol Allied Sci 19(1):13–18

    Article  CAS  PubMed  Google Scholar 

  17. Kearsley JH, Furlong KL, Cooke RA, Waters MJ (1990) An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers. Br J Cancer 61(6):821–827

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Janot F, Klijanienko J, Russo A et al (1996) Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis. Br J Cancer 73(4):531–538

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lazaris ACh, Rigopoulou A, Tseleni-Balafouta S et al (2002) Immunodetection and clinico-pathological correlates of two tumour growth regulators in laryngeal carcinoma. Histol Histopathol 17(1):131–138

    CAS  PubMed  Google Scholar 

  20. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by mononuclear antibody Ki-67. J Immunol 133:1710–1715

    CAS  PubMed  Google Scholar 

  21. Wintzer HO, Zipfel I, Schulte-Mönting J, Hellerich U, von Kleist S (1991) Ki-67 immunostaining in human breast tumors and its relationship to prognosis. Cancer 67(2):421–428

    Article  CAS  PubMed  Google Scholar 

  22. Tungekar MF, Gatter KC, Dunnill MS, Mason DY (1991) Ki-67 immunostaining and survival in operable lung cancer. Histopathology 19(6):545–550

    Article  CAS  PubMed  Google Scholar 

  23. Youssef EM, Matsuda T, Takada N et al (1995) Prognostic significance of the MIB-1 proliferation index for patients with squamous cell carcinoma of the esophagus. Cancer 76(3):358–366

    Article  CAS  PubMed  Google Scholar 

  24. Aaltomaa S, Lipponen P, Ala-Opas M, Eskelinen M, Syrjänen K (1997) Prognostic value of Ki-67 expression in renal cell carcinomas. Eur Urol 31(3):350–355

    CAS  PubMed  Google Scholar 

  25. Holte H, de Lange Davies C, Beiske K et al (1989) Ki67 and 4F2 antigen expression as well as DNA synthesis predict survival at relapse/tumour progression in low-grade B-cell lymphoma. Int J Cancer 44(6):975–980

    Article  CAS  PubMed  Google Scholar 

  26. Izawa H, Yonemitsu N, Shin T, Sugihara H (1999) Histopathological analysis of apoptosis, and expression of p53, bcl-2, bax, and Ki-67 in laryngeal squamous cell carcinomas and dysplasia. Auris Nasus Larynx 26(3):317–330

    Article  CAS  PubMed  Google Scholar 

  27. Krecicki T, Jeleń M, Zalesska-Krecicka M, Rak J, Szkudlarek T, Jeleń-Krzeszewska J (1999) Epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and Ki-67 antigen in laryngeal epithelial lesions. Oral Oncol 35(2):180–186

    Article  CAS  PubMed  Google Scholar 

  28. Sittel C, Eckel HE, Damm M, von Pritzbuer E, Kvasnicka HM (2000) Ki-67 (MIB1), p53, and Lewis-X (LeuM1) as prognostic factors of recurrence in T1 and T2 laryngeal carcinoma. Laryngoscope 110(6):1012–1017

    Article  CAS  PubMed  Google Scholar 

  29. Fumic-Dunkic L, Katic V, Janjanin S, Klapan I, Simuncic A, Vcev A (2003) Retrospective analysis of Ki-67 antigen expression in paraffin tissue blocks of laryngeal squamous cell carcinoma. Am J Otolaryngol 24(2):106–110

    Article  CAS  PubMed  Google Scholar 

  30. Sarafoleanu D, Postelnicu V, Iosif C, Manea C, Sarafoleanu C (2009) The role of p53, PCNA and Ki-67 as outcome predictors in the treatment of laryngeal cancer. J Med Life 2(2):219–226

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Re M, Zizzi A, Ferrante L et al (2014) p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival. Eur Arch Otorhinolaryngol 271(6):1641–1651

  32. Liu M, Lawson G, Delos M et al (2003) Predictive value of the fraction of cancer cells immunolabeled for proliferating cell nuclear antigen or Ki67 in biopsies of head and neck carcinomas to identify lymph node metastasis: comparison with clinical and radiologic examinations. Head Neck 25(4):280–288

    Article  PubMed  Google Scholar 

  33. Mirza S, Jeannon JP, Soames J, Wilson JA (2006) Is Ki67 a marker for the transformation of laryngeal dysplasia to carcinoma? Acta Otolaryngol 126(4):418–421

    Article  CAS  PubMed  Google Scholar 

  34. Rodrigues RB, Motta Rda R, Machado SM et al (2008) Prognostic value of the immunohistochemistry correlation of Ki-67 and p53 in squamous cell carcinomas of the larynx. Braz J Otorhinolaryngol 74(6):855–859

    PubMed  Google Scholar 

  35. Teppo H, Soini Y, Melkko J, Koivunen P, Alho OP (2003) Prognostic factors in laryngeal carcinoma: the role of apoptosis, p53, proliferation (Ki-67) and angiogenesis. APMIS 111(4):451–457

    Article  PubMed  Google Scholar 

  36. Kumar RV, Shenoy AM, Daniel R, Shah KV (2004) Cyclin D1, p53, MIB1, intratumoral microvessel density, and human papillomavirus in advanced laryngeal carcinoma: association with nodal metastasis. Otolaryngol Head Neck Surg 131(4):509–513

    Article  PubMed  Google Scholar 

  37. Kropveld A, Slootweg PJ, Blankenstein MA, Terhaard CH, Hordijk GJ (1998) Ki-67 and p53 in T2 laryngeal cancer. Laryngoscope 108(10):1548–1552

    Article  CAS  PubMed  Google Scholar 

  38. Ahmed WA, Suzuki K, Imaeda Y, Horibe Y (2008) Ki-67, p53 and epidermal growth factor receptor expression in early glottic cancer involving the anterior commissure treated with radiotherapy. Auris Nasus Larynx 35(2):213–219

    Article  PubMed  Google Scholar 

  39. Lothaire P, de Azambuja E, Dequanter D et al (2006) Molecular markers of head and neck squamous cell carcinoma: promising signs in need of prospective evaluation. Head Neck 28(3):256–269

    Article  PubMed  Google Scholar 

  40. Sakata K, Oouchi A, Nagakura H et al (2000) Accelerated radiotherapy for T1, 2 glottic carcinoma: analysis of results with KI-67 index. Int J Radiat Oncol Biol Phys 47(1):81–88

    Article  CAS  PubMed  Google Scholar 

  41. Saarilahti K, Kajanti M, Kouri M, Aaltonen LM, Franssila K, Joensuu H (2003) Cyclin A and Ki-67 expression as predictors for locoregional recurrence and outcome in laryngeal cancer patients treated with surgery and postoperative radiotherapy. Int J Radiat Oncol Biol Phys 57(4):986–995

    Article  CAS  PubMed  Google Scholar 

  42. Nichols AC, Whelan F, Basmaji J et al (2012) Ki-67 expression predicts radiotherapy failure in early glottic cancer. J Otolaryngol Head Neck Surg 41(2):124–130

    PubMed  Google Scholar 

  43. Lavertu P, Adelstein DJ, Myles J, Secic M (2001) P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy. Laryngoscope 111(11 Pt 1):1878–1892

    Article  CAS  PubMed  Google Scholar 

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None have any financial relationships to disclose.

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Authors and Affiliations

  1. Otolaryngology Department, University Hospital of Modena, Via del Pozzo 71, 41100, Modena, Italy

    Federico Maria Gioacchini, Matteo Alicandri-Ciufelli & Livio Presutti

  2. Otorhinolaryngology Department, Marche Polytechnic University, 60100, Ancona, Italy

    Massimo Re

  3. Department of Otorhinolaryngology ‘‘G. Ferreri’’, ‘‘La Sapienza’’ University, 00185, Rome, Italy

    Giuseppe Magliulo

  4. Pathologic Anatomy and Histopathology Division, Department of Biomedical Sciences and Public Health, Polytechnic University of the Marches, 60100, Ancona, Italy

    Corrado Rubini

Authors
  1. Federico Maria Gioacchini
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  2. Matteo Alicandri-Ciufelli
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  3. Giuseppe Magliulo
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  4. Corrado Rubini
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  5. Livio Presutti
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  6. Massimo Re
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Correspondence to Federico Maria Gioacchini.

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Gioacchini, F.M., Alicandri-Ciufelli, M., Magliulo, G. et al. The clinical relevance of Ki-67 expression in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 272, 1569–1576 (2015). https://doi.org/10.1007/s00405-014-3117-0

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  • DOI: https://doi.org/10.1007/s00405-014-3117-0

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