Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

Bascones-Martínez,Antonio; López-Durán,Mercedes; Cano‑Sánchez,Jorge; Sánchez-Verde,Lydia; Díez-Rodríguez,Ana; Aguirre-Echebarría,Pablo; Álvarez‑Fernández,Emilio; González-Moles,Miguel   Angel; Bascones‑Ilundain,Jaime; Lo Muzio,Lorenzo; Campo-Trapero,Julián

doi:10.3892/ol.2012.649

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

Authors:
- Antonio Bascones-Martínez
- Mercedes López-Durán
- Jorge Cano‑Sánchez
- Lydia Sánchez-Verde
- Ana Díez-Rodríguez
- Pablo Aguirre-Echebarría
- Emilio Álvarez‑Fernández
- Miguel Angel González-Moles
- Jaime Bascones‑Ilundain
- Lorenzo Lo Muzio
- Julián Campo-Trapero
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Affiliations: Department of Oral Surgery, Oral Medicine and Periodontology, Dental School, Complutense University of Madrid, Madrid, Spain, Inmunohistochemistry and Histology Unit, CNIO (Spanish National Cancer Centre), Madrid, Spain, Department of Pathology, Hospital Gregorio Marañón, Madrid, Spain, Department of Oral Medicine, Dental School, Granada University, Granada, Spain, Department of Surgical Sciences, University of Foggia, Foggia, Italy
Published online on: March 19, 2012 https://doi.org/10.3892/ol.2012.649
Pages: 1319-1325

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Abstract

Oncogene-induced senescence (OIS) may be a response to oncogenic activation, acting as a natural barrier against carcinogenesis at a premalignant stage. Thus, numerous cells in premalignant lesions enter senescence, but none or few in malignant tumours. This event could be due to the loss of senescence pathway effectors, including p16 (INK4a)-pRb or ARF-p53. The aim of this study was to characterize and compare the expression of certain senescent markers between oral precancer and cancer tissue samples. The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD-), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays. The expression of p16-pRb pathway markers, cyclin D1, maspin and Rb, was more frequent in OLD+ samples than in OSCC samples, although a statistical significance was only observed for maspin (P=0.036). Cyclin D1 expression was also significantly more frequent in OLD- samples vs. NOM samples. For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD- samples compared to in the NOM ones. These findings may indicate a role for cellular senescence in oral carcinogenesis, considering maspin as a reliable senescence marker and prognostic factor in oral premalignant lesions.

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1	Hayflick L and Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res. 25:585–621. 1961. View Article : Google Scholar : PubMed/NCBI
2	Ohtani N, Mann DJ and Hara E: Cellular senescence: its role in tumor suppression and aging. Cancer Sci. 100:792–797. 2009. View Article : Google Scholar : PubMed/NCBI
3	Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, et al: Tumour biology: senescence in premalignant tumours. Nature. 436:6422005. View Article : Google Scholar : PubMed/NCBI
4	Nickoloff BJ, Lingen MW, Chang BD, Shen M, Swift M, Curry J, et al: Tumor suppressor maspin is up-regulated during keratinocyte senescence, exerting a paracrine antiangiogenic activity. Cancer Res. 64:2956–2961. 2004. View Article : Google Scholar
5	Parkin DM, Pisani P and Ferlay J: Global cancer statistics. CA Cancer J Clin. 49:33–64. 1999. View Article : Google Scholar
6	Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M, et al: Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature. 436:725–730. 2005. View Article : Google Scholar : PubMed/NCBI
7	Michaloglou C, Vredeveld LC, Soengas MS, et al: BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 436:720–724. 2005. View Article : Google Scholar : PubMed/NCBI
8	Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, et al: Oncogene-induced senescence as an initial barrier in lymphoma development. Nature. 436:660–665. 2005. View Article : Google Scholar : PubMed/NCBI
9	Vered M, Allon I and Dayan D: Maspin, p53, p63, and Ki-67 in epithelial lesions of the tongue: from hyperplasia through dysplasia to carcinoma. J Oral Pathol Med. 38:314–320. 2009. View Article : Google Scholar : PubMed/NCBI
10	Soni S, Kaur J, Kumar A, Chakravarti N, Mathur M, Bahadur S, et al: Alterations of Rb pathway components are frequent events in patients with oral epithelial dysplasia and predict clinical outcome in patients with squamous cell carcinoma. Oncology. 68:314–325. 2005. View Article : Google Scholar : PubMed/NCBI
11	Itahana K, Dimri G and Campisi J: Regulation of cellular senescence by p53. Eur J Biochem. 268:2784–2789. 2001. View Article : Google Scholar : PubMed/NCBI
12	Shangary S, Qin D, McEachern D, Liu M, Miller RS, Qiu S, et al: Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proc Natl Acad Sci USA. 105:3933–3938. 2008. View Article : Google Scholar : PubMed/NCBI
13	Lavertu P, Adelstein DJ, Myles J and Secic M: P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy. Laryngoscope. 111:1878–1892. 2001. View Article : Google Scholar : PubMed/NCBI
14	Tu HF, Chen HW, Kao SY, Lin SC, Liu CJ and Chang KW: MDM2 SNP 309 and p53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation. Radiother Oncol. 87:243–252. 2008. View Article : Google Scholar : PubMed/NCBI
15	Huang SF, Chen IH, Liao CT, Wang HM, Liou SH and Hsieh LL: Combined effects of MDM2 SNP 309 and p53 mutation on oral squamous cell carcinomas associated with areca quid chewing. Oral Oncol. 45:16–22. 2009. View Article : Google Scholar : PubMed/NCBI
16	Campo-Trapero J, Cano-Sánchez J, Palacios-Sánchez B, Sánchez-Gutiérrez JJ, González-Moles MA and Bascones-Martínez A: Update on molecular pathology in oral cancer and precancer. Anticancer Res. 28:1197–1205. 2008.PubMed/NCBI
17	El-Naggar AK, Lai S, Clayman GL, Zhou JH, Tucker SA, Myers J, et al: Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications. Hum Pathol. 30:1013–1018. 1999. View Article : Google Scholar : PubMed/NCBI
18	Liu HS, Lu HH, Lui MT, Yu EH, Shen W, Chen YP, et al: Detection of copy number amplification of cyclin D1 (CCND1) and cortactin (CTTN) in oral carcinoma and oral brushed samples from areca chewers. Oral Oncol. 45:1032–1036. 2009. View Article : Google Scholar : PubMed/NCBI
19	Myo K, Uzawa N, Miyamoto R, Sonoda I, Yuki Y and Amagasa T: Cyclin D1 gene numerical aberration is a predictive marker for occult cervical lymph node metastasis in TNM stage I and II squamous cell carcinoma of the oral cavity. Cancer. 104:2709–2716. 2005. View Article : Google Scholar : PubMed/NCBI
20	De Vicente JC, Herrero-Zapatero A, Fresno MF and López-Arranz JS: Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance. Oral Oncol. 38:301–308. 2002.PubMed/NCBI
21	Sathyan KM, Nalinakumari KR, Abraham T and Kannan S: CCND1 polymorphisms (A870G and C1722G) modulate its protein expression and survival in oral carcinoma. Oral Oncol. 44:689–697. 2008. View Article : Google Scholar : PubMed/NCBI
22	Marioni G, Gaio E, Giacomelli L, Bertolin A, D’Alessandro E, Stramare R, et al: Maspin subcellular localization and expression in oral cavity squamous cell carcinoma. Eur Arch Otorhinolaryngol. 265:S97–104. 2008. View Article : Google Scholar : PubMed/NCBI
23	Cho JH, Kim HS, Park CS, Kim JK, Jung KY, Shin BK, et al: Maspin expression in early oral tongue cancer and its relation to expression of mutant-type p53 and vascular endothelial growth factor (VEGF). Oral Oncol. 43:272–277. 2007. View Article : Google Scholar : PubMed/NCBI
24	Yasumatsu R, Nakashima T, Hirakawa N, Kumamoto Y, Kuratomi Y, Tomita K, et al: Maspin expression in stage I and II oral tongue squamous cell carcinoma. Head Neck. 23:962–966. 2001. View Article : Google Scholar : PubMed/NCBI