Abstract
Objectives
Gene products, which show a significant association to cell proliferation and cell cycle control, are of high scientific interest, because genes as well as gene products could be possible targets for a specific therapeutic approach and eventually be prognostic markers.
Materials and methods
Cyclin D1 expression and amplification as well as the Ki-67 expression status were examined in a two tissue microarray analysis for head and neck squamous cell carcinoma (HNSCC) including 546 patients. A tumour site-specific analysis and a survival analysis of 222 oral squamous cell carcinoma (OSCC) patients were performed. Cyclin D1 amplification status was examined with fluorescence in situ hybridisation analysis, while cyclin D1 expression and Ki-67 expression status were examined with IHC.
Results
Amplification of the CCND1 gene and immunohistochemical expression of cyclin D1 and Ki-67 were examined in 546 tumours of the head and neck region in two tissue microarrays. CCND1 amplification was significantly more frequent in pharyngeal carcinomas (63 %) than in laryngeal (37 %) and oral (25 %) carcinomas. Among the 222 cases of OSCCs, both CCND1 amplification and cyclin D1 expression were significantly associated with overall survival of the patients (p = 0.0127 and p = 0.0004, respectively). Ki-67 expression was significantly associated with cyclin D1 expression and with amplification of the CCND1 gene (p = 0.0002 and p = 0.0015, respectively) but not with patient overall survival.
Conclusion
Our results suggest the prognostic value of CCND1 amplification and cyclin D1 expression for patients with OSCC and highlight the genetic differences in HNSCC of different subanatomic localisation.
Clinical relevance
Cyclin D1 expression and CCND1 amplification seem to have a prognostic value for OSCC. Further studies of HNSCC should always consider subanatomic genetic differences.
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References
Grimm M, Krimmel M, Alexander D, Munz A, Kluba S, Keutel C et al (2012) Prognostic value of histamine H1 receptor expression in oral squamous cell carcinoma. Clin Oral Investig. doi:10.1007/s00784-012-0784-3
Freier K, Sticht C, Hofele C, Flechtenmacher C, Stange D, Puccio L et al (2006) Recurrent coamplification of cytoskeleton-associated genes EMS1 and SHANK2 with CCND1 in oral squamous cell carcinoma. Gene Chromosome Cancer 45:118–125
Ishiguro R, Fujii M, Yamashita T, Tashiro M, Tomita T, Ogawa K et al (2003) CCND1 amplification predicts sensitivity to chemotherapy and chemoradiotherapy in head and neck squamous cell carcinoma. Anticancer Res 23:5213–5220
Fujii M, Ishiguro R, Yamashita T, Tashiro M (2001) Cyclin D1 amplification correlates with early recurrence of squamous cell carcinoma of the tongue. Cancer Lett 172:187–192
Xu J, Gimenez-Conti IB, Cunningham JE, Collet AM, Luna MA, Lanfranchi HE et al (1998) Alterations of p53, cyclin D1, Rb, and H-ras in human oral carcinomas related to tobacco use. Cancer 83:204–212
Shintani S, Mihara M, Nakahara Y, Kiyota A, Ueyama Y, Matsumura T et al (2002) Expression of cell cycle control proteins in normal epithelium, premalignant and malignant lesions of oral cavity. Oral Oncol 38:235–243
Rousseau A, Lim MS, Lin Z, Jordan RC (2001) Frequent cyclin D1 gene amplification and protein overexpression in oral epithelial dysplasias. Oral Oncol 37:268–275
Lam KY, Ng IO, Yuen AP, Kwong DL, Wei W (2000) Cyclin D1 expression in oral squamous cell carcinomas: clinicopathological relevance and correlation with p53 expression. J Oral Pathol Med 29:167–172
Goto H, Kawano K, Kobayashi I, Sakai H, Yanagisawa S (2002) Expression of cyclin D1 and GSK-3beta and their predictive value of prognosis in squamous cell carcinomas of the tongue. Oral Oncol 38:549–556
Miyamoto R, Uzawa N, Nagaoka S, Hirata Y, Amagasa T (2003) Prognostic significance of cyclin D1 amplification and overexpression in oral squamous cell carcinomas. Oral Oncol 39:610–618
Carlos de Vicente J, Herrero-Zapatero A, Fresno MF, Lopez-Arranz JS (2002) Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance. Oral Oncol 38:301–308
Angadi PV, Krishnapillai R (2007) Cyclin D1 expression in oral squamous cell carcinoma and verrucous carcinoma: correlation with histological differentiation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:e30–e35
Fracchiolla NS, Pruneri G, Pignataro L, Carboni N, Capaccio P, Boletini A et al (1997) Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: correlation of protein expression with lymph node metastases and advanced clinical stage. Cancer 79:1114–1121
Fortin A, Guerry M, Guerry R, Talbot M, Parise O, Schwaab G et al (1997) Chromosome 11q13 gene amplifications in oral and oropharyngeal carcinomas: no correlation with subclinical lymph node invasion and disease recurrence. Clin Cancer Res 3:1609–1614
Nakahara Y, Shintani S, Mihara M, Kiyota A, Ueyama Y, Matsumura T (2000) Alterations of Rb, p16(INK4A) and cyclin D1 in the tumorigenesis of oral squamous cell carcinomas. Cancer Lett 160:3–8
Koontongkaew S, Chareonkitkajorn L, Chanvitan A, Leelakriangsak M, Amornphimoltham P (2000) Alterations of p53, pRb, cyclin D(1) and cdk4 in human oral and pharyngeal squamous cell carcinomas. Oral Oncol 36:334–339
Bova RJ, Quinn DI, Nankervis JS, Cole IE, Sheridan BF, Jensen MJ et al (1999) Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue. Clin Cancer Res 5:2810–2819
Hardisson D (2003) Molecular pathogenesis of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol 260:502–508
Bettendorf O, Piffko J, Bankfalvi A (2004) Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy? Oral Oncol 40:110–119
Yu Z, Weinberger PM, Haffty BG, Sasaki C, Zerillo C, Joe J et al (2005) Cyclin d1 is a valuable prognostic marker in oropharyngeal squamous cell carcinoma. Clin Cancer Res 11:1160–1166
Michalides RJ, van Veelen NM, Kristel PM, Hart AA, Loftus BM, Hilgers FJ et al (1997) Overexpression of cyclin D1 indicates a poor prognosis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 123:497–502
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 the monoclonal antibody Ki-67. J Immunol 133:1710–1715
Ruiz C, Seibt S, Al Kuraya K, Siraj AK, Mirlacher M, Schraml P et al (2006) Tissue microarrays for comparing molecular features with proliferation activity in breast cancer. Int J Cancer 118:2190–2194
Myoung H, Kim MJ, Lee JH, Ok YJ, Paeng JY, Yun PY (2006) Correlation of proliferative markers (Ki-67 and PCNA) with survival and lymph node metastasis in oral squamous cell carcinoma: a clinical and histopathological analysis of 113 patients. Int J Oral Maxillofac Surg 35:1005–1010
Pich A, Chiusa L, Navone R (2004) Prognostic relevance of cell proliferation in head and neck tumors. Ann Oncol 15:1319–1329
Xie X, Clausen OP, De Angelis P, Boysen M (1999) The prognostic value of spontaneous apoptosis, Bax, Bcl-2, and p53 in oral squamous cell carcinoma of the tongue. Cancer 86:913–920
Piffko J, Bankfalvi A, Ofner D, Kusch F, Bocker W, Joos U et al (1996) In situ assessment of cell proliferation at the invasive front of oral squamous cell carcinomas. Virchows Arch 429:229–234
Girod SC, Pfeiffer P, Ries J, Pape HD (1998) Proliferative activity and loss of function of tumour suppressor genes as ‘biomarkers’ in diagnosis and prognosis of benign and preneoplastic oral lesions and oral squamous cell carcinoma. Br J Oral Maxillofac Surg 36:252–260
Sittel C, Ruiz S, Volling P, Kvasnicka HM, Jungehulsing M, Eckel HE (1999) Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity. Oral Oncol 35:583–589
Xie X, De Angelis P, Clausen OP, Boysen M (1999) Prognostic significance of proliferative and apoptotic markers in oral tongue squamous cell carcinomas. Oral Oncol 35:502–509
Elsheikh S, Green AR, Aleskandarany MA, Grainge M, Paish CE, Lambros MB et al (2007) CCND1 amplification and cyclin D1 expression in breast cancer and their relation with proteomic subgroups and patient outcome. Breast Cancer Res Treat 109(2):325–335
Holst F, Stahl PR, Ruiz C, Hellwinkel O, Jehan Z, Wendland M et al (2007) Estrogen receptor alpha (ESR1) gene amplification is frequent in breast cancer. Nat Genet 39:655–660
Freier K, Bosch FX, Flechtenmacher C, Devens F, Benner A, Lichter P et al (2003) Distinct site-specific oncoprotein overexpression in head and neck squamous cell carcinoma: a tissue microarray analysis. Anticancer Res 23:3971–3977
Wang MB, Alavi S, Engstrom M, Lee J, Namazie A, Moatamed F et al (1999) Detection of chromosome 11q13 amplification in head and neck cancer using fluorescence in situ hybridization. Anticancer Res 19:925–931
Akervall JA, Jin Y, Wennerberg JP, Zatterstrom UK, Kjellen E, Mertens F et al (1995) Chromosomal abnormalities involving 11q13 are associated with poor prognosis in patients with squamous cell carcinoma of the head and neck. Cancer 76:853–859
Kyomoto R, Kumazawa H, Toda Y, Sakaida N, Okamura A, Iwanaga M et al (1997) Cyclin-D1-gene amplification is a more potent prognostic factor than its protein over-expression in human head-and-neck squamous-cell carcinoma. Int J Cancer 74:576–581
Hofele C, Joos S, Flechtenmacher C, Bosch FX, Lichter P, Muhling J et al (2002) Opportunities and chances for tissue chip microarrays in head and neck surgery. A novel technique for the rapid evaluation of potentially novel biomarkers. Mund Kiefer Gesichtschir 6:394–401
Silva SD, Agostini M, Nishimoto IN, Coletta RD, Alves FA, Lopes MA et al (2004) Expression of fatty acid synthase, ErbB2 and Ki-67 in head and neck squamous cell carcinoma. A clinicopathological study. Oral Oncol 40:688–696
Franchi A, Gallo O, Boddi V, Santucci M (1996) Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination. Clin Cancer Res 2:1801–1808
Liu M, Lawson G, Delos M, Jamart J, Chatelain B, Remacle M et al (2003) Prognostic value of cell proliferation markers, tumour suppressor proteins and cell adhesion molecules in primary squamous cell carcinoma of the larynx and hypopharynx. Eur Arch Otorhinolaryngol 260:28–34
Koelbl O, Rosenwald A, Haberl M, Muller J, Reuther J, Flentje M (2001) p53 and Ki-67 as predictive markers for radiosensitivity in squamous cell carcinoma of the oral cavity? an immunohistochemical and clinicopathologic study. Int J Radiat Oncol Biol Phys 49:147–154
Roland NJ, Caslin AW, Nash J, Stell PM (1992) Value of grading squamous cell carcinoma of the head and neck. Head Neck 14:224–229
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Hanken, H., Gröbe, A., Cachovan, G. et al. CCND1 amplification and cyclin D1 immunohistochemical expression in head and neck squamous cell carcinomas. Clin Oral Invest 18, 269–276 (2014). https://doi.org/10.1007/s00784-013-0967-6
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DOI: https://doi.org/10.1007/s00784-013-0967-6