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European Archives of Oto-Rhino-Laryngology

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01-11-2013 | Head and Neck

From laryngeal epithelial precursor lesions to squamous carcinoma of the larynx: the role of cell cycle proteins and β-catenin

Authors: Fernando López, César Álvarez-Marcos, Marta Alonso-Guervós, Francisco Domínguez, Carlos Suárez, Mario A. Hermsen, José L. Llorente

Published in: European Archives of Oto-Rhino-Laryngology | Issue 12/2013

Abstract

Novel markers to accurately predict the risk of malignant transformation in laryngeal epithelial precursor lesions (EPL) are needed. We tried to identify some molecular alterations occurring in laryngeal tumorigenesis. In this study, 60 paraffin-embedded EPL and 17 metachronous invasive carcinomas were immunostained for markers associated with proliferation (Ki67), cell cycle control (p53, p21, p16, p27, cyclin D1), and cell adhesion and invasion (laminin and β-catenin). Aberrant expression of p16 and p53 and positivity at cytoplasm for β-catenin and cyclin D1 were detected significantly in EPL with progression to invasive laryngeal carcinoma. All cases with basal and suprabasal reactivity of p53 showed β-catenin overexpression. We found that β-catenin protein expression increased significantly with the grade of dysplasia. This is one of the studies with the largest number of laryngeal EPL and invasive carcinoma studied sequentially. Our data confirm the role of some cell cycle regulatory proteins in the development of laryngeal carcinoma. Cytoplasmic retention of β-catenin in EPL seems to be related with more aggressive biological behavior. Combined increased p53 and cytoplasmic β-catenin protein expression could be biologically important in laryngeal tumorigenesis. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S et al (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56:2488–2492PubMed

Rodrigo JP, García Pedrero JM, Suárez C, Takes RP, Thompson LDR, Sloootweg PJ et al (2012) Biomarkers predicting malignant progression of laryngeal epithelial precursor lesion: a systematic review. Eur Arch Otolaryngol 269:1073–1083CrossRef

Papadimitrakopoulou V, Izzo JG, Liu DD, Myers J, Ceron TL, Lewin J et al (2009) Cyclin D1 and cancer development in laryngeal premalignancy patients. Cancer Prev Res 2:14–21CrossRef

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

Visser R, van der Beek JM, Havenith MG, Cleutjens JP, Bosman FT (1986) Immunocytochemical detection of basement membrane antigens in the histopathological evaluation of laryngeal dysplasia and neoplasia. Histopathology 10:171–180PubMedCrossRef

Rodrigo JP, Domínguez F, Álvarez C, Manrique C, Herrero A, Suárez C (2002) Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features. Eur J Cancer 38:1059–1064PubMedCrossRef

Remacle M, Eckel HE, Antonelli A, Brasnu D, Chevalier D, Friedrich G et al (2000) Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society. Eur Arch Otorhinolaryngol 257:227–231PubMedCrossRef

Cruz I, Napier SS, van der Waal I, Snijders PJ, Walboomers JM, Lamey PJ et al (2002) Suprabasal p53 immunoexpression is strongly associated with high grade dysplasia and risk for malignant transformation in potentially malignant oral lesions from Northern Ireland. J Clin Pathol 55:98–104PubMedCrossRef

Geradts J, Wilson PA (1996) High frequency of aberrant p16(INK4A) expression in human breast cancer. Am J Pathol 149:15–20PubMed

10.

Jeannon JP, Soames JV, Aston V, Stafford FW, Wilson JA (2004) Molecular markers in dysplasia of the larynx: expression of cyclin-dependent kinase inhibitors p21, p27 and p53 tumour suppressor gene in predicting cancer risk. Clin Otolaryngol Allied Sci 29:698–704PubMedCrossRef

11.

Fan GK, Fujieda S, Sunaga H, Tsuzuki H, Ito N, Saito H (1999) Expression of protein p27 is associated with progression and prognosis in laryngeal cancer. Laryngoscope 109:815–820PubMedCrossRef

12.

Rodrigo JP, Álvarez-Alija G, Menéndez ST, Mancebo G, Allonca E, García-Carracedo D et al (2011) Cortactin and focal adhesion kinase as predictors of cancer risk in patients with laryngeal premalignancy. Cancer Prev Res 4:1333–1341CrossRef

13.

Mielcarek-Kuchta D, Olofsson J, Golusinski W (2008) Laminin expression in advanced laryngeal squamous cell carcinoma does not correlate to neck metastases. Eur Arch Otorhinolaryngol 265:1257–1261PubMedCrossRef

14.

Hsu PK, Li AF, Wang YC, Hsieh CC, Huang MH, Hsu WH et al (2008) Reduced membranous beta-catenin protein expression is associated with metastasis and poor prognosis in squamous cell carcinoma of the esophagus. J Thorac Cardiovasc Surg 135:1029–1035PubMedCrossRef

15.

Pignataro L, Capaccio P, Pruneri G, Carboni N, Buffa R, Neri A et al (1998) The predictive value of p53, MDM-2, cyclin D1 and Ki67 in the progression from low-grade dysplasia towards carcinoma of the larynx. J Laryngol Otol 112:455–459PubMedCrossRef

16.

Cabanillas R, Rodrigo JP, Ferlito A, Rinaldo A, Fresno MF, Aguilar C et al (2007) Is there an epidemiological link between human papillomavirus DNA and basaloid squamous cell carcinoma of the pharynx? Oral Oncol 43:327–332PubMedCrossRef

17.

Gale N, Michaels L, Luzar B, Poljak M, Zidar N, Fischinger J et al (2009) Current review on squamous intraepithelial lesions of the larynx. Histopathology 54:639–656PubMedCrossRef

18.

Eversole LR (2009) Dysplasia of the upper aerodigestive tract squamous epithelium. Head Neck Pathol 3:63–68PubMedCrossRef

19.

Sadri M, McMahon J, Parker A (2006) Management of laryngeal dysplasia: a review. Eur Arch Otorhinolaryngol 263:843–852PubMedCrossRef

20.

Zhang HK, Liu HG (2012) Is severe dysplasia the same lesion as carcinoma in situ? 10-Year follow-up of laryngeal precancerous lesions. Acta Otolaryngol 132:325–328PubMedCrossRef

21.

Rodrigo JP, García-Carracedo D, García LA, Menéndez S, Allonca E, González MV et al (2009) Distinctive clinicopathological associations of amplification of the cortactin gene at 11q13 in head and neck squamous cell carcinomas. J Pathol 217:516–523PubMedCrossRef

22.

Álvarez Marcos C, Domínguez Iglesias F, Sampedro Nuño A (2009) Neoplasias intraepiteliales potencialmente invasivas de cabeza y cuello. Clínica, diagnóstico y tratamiento. In: Carlos Suárez, Luis Mª Gil-Carcedo García, Jaime Marco, Jesús E. Medina, Primitivo Ortega, Juan Trinidad (eds) Tratado de otorrinolaringología y cirugía de cabeza y cuello, 2nd edn. Panamericana, Madrid

23.

Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11:9–22PubMedCrossRef

24.

Boyle JO, Hakim J, Koch W, van der Riet P, Hruban RH, Roa RA et al (1993) The incidence of p53 mutations increases with progression of head and neck cancer. Cancer Res 53:4477–4480PubMed

25.

Gallo O, Santucci M, Franchi A (1997) Cumulative prognostic value of p16/CDKN2 and p53 oncoprotein expression in premalignant laryngeal lesions. J Natl Cancer Inst 89:1161–1163PubMedCrossRef

26.

Braakhuis BJM, Tabor MP, Kummer JA, Kummer A, Leemans R, Brakenhoff RH (2003) A genetic explanation of Slaughter’s concept of field cancerization. Cancer Res 63:1727–1730PubMed

27.

Marcos CÁ, Alonso-Guervós M, Prado NR, Gimeno TS, Iglesias FD, Hermsen M et al (2011) Genetic model of transformation and neoplastic progression in laryngeal epithelium. Head Neck 33:216–224PubMedCrossRef

28.

Li X, Gao L, Li H, Gao J, Yang Y, Zhou F et al (2013) Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis. J Infect Dis 207:479–488PubMedCrossRef

29.

Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, et al (2012) Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region. Head Neck doi:10.1002/hed.22015 (Epub ahead of print)

30.

Schoelch ML, Regezi JA, Dekker NP, Ng IO, McMillan A, Ziober BL et al (1999) Cell cycle proteins and the development of oral squamous cell carcinoma. Oral Oncol 35:333–342PubMedCrossRef

31.

Nusse R (2005) Wnt signaling in disease and in development. Cell Res 15:28–32PubMedCrossRef

32.

Galera-Ruiz H, Ríos-Moreno MJ, González-Cámpora R, Ortega I, Fernández A, García-Escudero A et al (2012) The cadherin–catenin complex in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 269:1183–1188PubMedCrossRef

33.

Gouliomous AK, Varakis J, Goumas P, Papadaki H (2010) Deferential β-catenin expression between glottis and supraglottic laryngeal carcinoma. Eur Arch Otorhinolaryngol 267:1573–1578CrossRef

34.

Harris SL, Levine AJ (2005) The p53 pathway: positive and negative feedback loops. Oncogene 24:2899–2908PubMedCrossRef

35.

Hagedorn HG, Sauer U, Schleicher ED, Nerlich AG (2001) Divergence in distribution and prognostic significance of major basement components in laryngeal carcinomas. Int J Oncol 18:1045–1051PubMed

Title: From laryngeal epithelial precursor lesions to squamous carcinoma of the larynx: the role of cell cycle proteins and β-catenin
Authors: Fernando López
César Álvarez-Marcos
Marta Alonso-Guervós
Francisco Domínguez
Carlos Suárez
Mario A. Hermsen
José L. Llorente
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: European Archives of Oto-Rhino-Laryngology / Issue 12/2013
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-013-2476-2

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From laryngeal epithelial precursor lesions to squamous carcinoma of the larynx: the role of cell cycle proteins and β-catenin

Abstract

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Abstract

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