Abstract
Background
Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor etiologically related to professional exposure to wood dust. The overall prognosis is poor, mainly due to the difficulty to resect the tumor completely in this anatomically complex region. Therefore, there is great need for alternative treatments. However, the lack of a good tumor model system for ITAC has hampered the development and testing of new therapeutic agents. Here, we report the establishment and characterization of the first human ITAC cell line named ITAC-3.
Methods
The cell line was initiated from small explants of a T4bN0M0 colonic type ITAC from the ethmoid sinus. Growth and invasion parameters as well as genetic characteristics were analyzed.
Results
The population doubling time was 18 h and the cell line was capable of invasion in matrigel. Chromosomal analysis showed a tetraploid karyotype with both numerical and structural aberrations. High resolution microarray CGH analysis identified many copy number alterations, including homozygous deletions. TP53 carried a mutation c.818G>T in exon eight concurring with a strong nuclear protein overexpression. Immunohistochemical analysis showed protein overexpression of EGFR and normal expression of β-catenin and p16.
Conclusion
This is the first report of the establishment of a cell line derived from a primary ITAC. The genomic profile of the cell line was the same as the primary tumor from which it was derived. This new cell line will be a useful tool for the development and testing of new therapeutic agents for this tumor type.
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References
D.M. Alessi, T.K. Trapp, Y.S. Fu, T.C. Calcaterra, Nonsalivary sinonasal adenocarcinoma. Arch Otolaryngol Head Neck Surg 114, 996–999 (1998)
M. Ariza, J.L. Llorente, C. Alvarez-Marcos, L. Baragaño, A. Salas, N. Rodriguez Prado et al., Comparative genomic hybridization in primary sinonasal adenocarcinomas. Cancer 100, 335–341 (2004)
T.E. Buffart, D. Israeli, M. Tijssen, S.J. Vosse, A. Mrsić, G.A. Meijer et al., Across array comparative genomic hybridization: a strategy to reduce reference channel hybridizations. Genes Chromosom Cancer 47, 994–1004 (2008)
M. Bussi, C.F. Gervasio, E. Riontino, G. Valente, L. Ferrari, E. Pira et al., Study of ethmoidal mucosa in a population at occupational high risk of sinonasal adenocarcinoma. Acta Otolaringol 122, 197–201 (2002)
H.R. Choi, E.M. Sturgis, A. Rashid, F. DeMonte, M.A. Luna, J.G. Batsakis et al., Sinonasal adenocarcinoma: evidence for histogenetic divergence of the enteric and nonenteric phenotypes. Hum Pathol 34, 1101–1107 (2003)
O. Choussy, C. Ferron, P.O. Védrine, B. Toussaint, B. Liétin, P. Marandas, GETTEC Study Group et al., Adenocarcinoma of ethmoid: a GETTEC retrospective multicenter study of 418 cases. Laryngoscope 118, 437–443 (2008)
A. Gelbard, M.E. Kupferman, S.A. Jasser, W. Chen, A.K. El-Naggar, J.N. Myers et al., An orthotopic murine model of sinonasal malignancy. Clin Cancer Res 14, 7348–7357 (2008)
A. Franchi, M. Santucci, B. Wenig, Adenocarcinoma, in Pathology and genetics of head and neck tumors, World health organization classification of tumors, ed. by L. Barnes, J.W. Eveson, P. Reichart, D. Sidransky, 5th edn. (IARC, Lyon, 2005), pp. 20–23
A. Franchi, C. Fondi, M. Paglierani, M. Pepi, O. Gallo, M. Santucci, Epidermal growth factor receptor expression and gene copy number in sinonasal intestinal type adenocarcinoma. Oral Oncol 45, 835–838 (2009)
M. Frattini, F. Perrone, S. Suardi, D. Balestra, S. Caramuta, F. Colombo et al., Phenotype-genotype correlation: challenge of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Head Neck 28, 909–915 (2006)
M.A. Hermsen, J.L. Llorente, J. Pérez-Escuredo, F. López, B. Ylstra, C. Alvarez-Marcos et al., Genome-wide analysis of genetic changes in intestinal-type sinonasal adenocarcinoma. Head Neck 31, 290–297 (2009)
M.A.J.A. Hermsen, A. Snijders, M. Alonso Guervós, S. Taenzer, U. Koerner, J. Baak et al., Centromeric chromosomal translocations show tissue-specific differences between squamous cell carcinomas and adenocarcinomas. Oncogene 24, 1571–1579 (2005)
R. Holmila, J. Bornholdt, T Suitiala, D. Cyr, M. Dictor, T. Steiniche et al., Profile of TP53 gene mutations in sinonasal cancer. Mutat. Res. (2009). [Epub ahead of print]
R. Holmila, D. Cyr, D. Luce, P. Heikkilä, M. Dictor, T. Steiniche et al., COX-2 and p53 in human sinonasal cancer: COX-2 expression is associated with adenocarcinoma histology and wood-dust exposure. Int J Cancer 122, 2154–2159 (2008)
R. Holmila, J. Bornholdt, P. Heikkilä, T. Suitiala, J. Févotte, D. Cyr, et al. Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer. Int. J. Cancer (2009). [Epub ahead of print]
O. Kleinsasser, H.G. Schroeder, Adenocarcinomas of the inner nose after exposure to wood dust. Morphological findings and relationships between histopathology and clinical behavior in 79 cases. Arch Otorhinolaringol 245, 1–15 (1988)
D. Korinth, M. Pacyna-Gengelbach, N. Deutschmann, S. Hattenberger, U. Bockmühl, M. Dietel et al., Chromosomal imbalances in wood dust-related adenocarcinomas of the inner nose and their associations with pathological parameters. J Pathol 207, 207–215 (2005)
R.J. Leary, J.C. Lin, J. Cummins, S. Boca, L.D. Wood, D.W. Parsons et al., Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. Proc Natl Acad Sci USA 105, 16224–16229 (2008)
L. Licitra, S. Suardi, P. Bossi, L.D. Locati, L. Mariani, P. Quattrone et al., Prediction of TP53 status for primary cisplatin, fluorouracil, and leucovorin chemotherapy in ethmoid sinus intestinal-type adenocarcinoma. J Clin Oncol 22, 4901–4906 (2004)
J.L. Llorente, J. Pérez-Escuredo, C. Alvarez-Marcos, C. Suárez, M. Hermsen, Genetic and clinical aspects of wood dust related intestinal-type sinonasal adenocarcinoma: a review. Eur Arch Otorhinolaryngol 266, 1–7 (2009)
J.G. Martínez, J. Pérez-Escuredo, F. López, C. Suárez, C. Alvarez-Marcos, J.L. Llorente et al., Microsatellite instability analysis of sinonasal carcinomas. Otolaryngol Head Neck Surg 140, 55–60 (2009)
C.D. McKinney, S.E. Mills, D.W. Franquemont, Sinonasal intestinal-type adenocarcinoma: immunohistochemical profile and comparison with colonic adenocarcinoma. Mod Pathol 8, 421–6 (1995)
F. Núñez, C. Suárez, I. Alvarez, J.L. Losa, P. Barthe, M. Fresno, Sinonasal adenocarcinoma: epidemiological and clinico-pathological study of 34 cases. J Otolaryngol 22, 86–90 (1993)
J.A. Ozolek, E.L. Barnes, J.L. Hunt, Basal/myoepithelial cells in chronic sinusitis, respiratory epithelial adenomatoid hamartoma, inverted papilloma, and intestinal-type and nonintestinal-type sinonasal adenocarcinoma: an immunohistochemical study. Arch Pathol Lab Med 131, 530–537 (2007)
P. Pérez, O. Domínguez, S. González, A. Triviño, C. Suárez, Ras gene mutations in ethmoid sinus adenocarcinoma: prognostic implications. Cancer 86, 255–264 (1999)
B. Perez-Ordonez, N.N. Huynh, K.W. Berean, R.C.K. Jordan, Expression of mismatch repair proteins, β-catenin, and E-cadherin in intestinal-type sinonasal adenocarcinoma. J Clin Pathol 57, 1080–1083 (2005)
F. Perrone, M. Oggionni, S. Birindelli, S. Suardi, S. Tabano, R. Romano et al., TP53, p14ARF, p16INK4a and H-ras gene molecular analysis in intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Int J Cancer 105, 196–203 (2003)
F.X. Roux, D. Brasnu, B. Devaux, E. Chabardes, G. Schwaab, O. Laccourreye et al., Ethmoide sinus carcinomas: results and prognosis after neoadjuvant chemoterapy and combined surgery. A 10-year experience. Surg Neurol 42, 98–104 (1994)
A.T. Saber, L.R. Nielsen, M. Dictor, L. Hagmar, Z. Mikoczy, H. Wallin, K-ras mutations in sinonasal adenocarcinomas in patients occupationally exposed to wood dust or leather dust. Cancer Lett 126, 59–65 (1998)
C. Suarez, J.L. Llorente, R. Fernandez De Leon, E. Maseda, A. Lopez, Prognostic factors in sinonasal tumours involving the anterior skull base. Head Neck 26, 136–144 (2004)
G. Valente, L. Ferrari, S. Kerim, C.F. Gervasio, E. Ricci, G. Migliaretti et al., Evidence of p53 immunohistochemical overexpression in ethmoidal mucosa of woodworkers. Cancer Detect Prev 28, 99–106 (2004)
A. Varshavsky, Targeting the absence: homozygous DNA deletions as immutable signposts for cancer therapy. Proc Natl Acad Sci USA 104, 14935–14940 (2007)
J. Wolf, P. Schmezer, D. Fengel, H.G. Schroeder, H. Scheithauer, P. Woeste, The role of combination effects on the etiology of malignant nasal tumours in the wood-working industry. Acta Otolaryngol 535, 3–16 (1998)
T.T. Wu, L. Barnes, A. Bakker, P.A. Swalsky, S.D. Finkelstein, K-ras-2 and P53 genotyping of intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses. Mod Pathol 9, 199–204 (1996)
S.S. Yom, A. Rashid, D.I. Rosenthal, D.D. Elliott, E.Y. Hanna, R.S. Weber et al., Genetic analysis of sinonasal adenocarcinoma phenotypes: distinct alterations of histogenetic significance. Mod Pathol 18, 315–319 (2005)
Acknowledgements
This work was supported by grants PI05-1387, PI08-1599 and EMER07-048 of Fondos de Investigación Sanitaria (FIS) and RD06/0020/0034 of Red Temática de Investigación Cooperativa en Cáncer (RTICC), Spain. JPE was supported by the Spanish Ministry of Science and Innovation (MICINN), co financed by the European Social Fund.
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Pérez-Escuredo, J., García Martínez, J., García-Inclán, C. et al. Establishment and genetic characterization of an immortal tumor cell line derived from intestinal-type sinonasal adenocarcinoma. Cellular Onc. 34, 23–31 (2011). https://doi.org/10.1007/s13402-010-0002-8
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DOI: https://doi.org/10.1007/s13402-010-0002-8