An 8-year-old male pug with a 12-month history of a progressive nonpainful mass on the left cornea was evaluated. Ocular examination showed a severe bilateral keratoconjunctivitis sicca, pigmentary keratitis, and an exophytic irregular pink mass occupying approximately 75% of the total corneal surface of the left eye. A squamous cell carcinoma (SCC) was suspected on cytology, and clinical investigations showed no evidence of metastases. A transpalpebral enucleation was therefore performed, and the diagnosis of SCC was confirmed on histopathology. Immunohistochemical investigations showed that the neoplastic cells were pan-cytokeratin positive and vimentin negative. Additionally, nuclei immunoreactive to Ki-67 antigen were detected. Tumor cells were also negative to p53. Immunoreactivity to COX-2 was found in less than 10% of the neoplastic cells. No adjuvant therapies were instituted, and no evidence of local recurrence or distance metastasis was identified during the 24-month follow-up period. 1. Introduction Neoplasms of the cornea occur uncommonly in dogs although various primary and secondary tumors have been described in veterinary literature [1, 2]. Corneal squamous cell carcinoma (SCC) is considered rare in the dog and often represents a secondary extension of a primary limbal or conjunctival neoplasia [1, 3, 4]. A number of cases of canine primary SCC of the cornea have been described especially in recent years [5–10], and some authors report an increased occurrence of the tumor in this period [11]. Only three canine SCCs have been characterized by the use of immunohistochemistry, and p53 protein was generally investigated with varying results [7, 9]. Cyclooxygenase (COX) overexpression has been identified in various neoplastic tissues in humans [12–18] and domestic animals [19–26]. COX-2 has been found to be strongly expressed in all the cases of canine SCC of the cutis [27]. Since the etiopathogenesis of ocular SCC is still unclear, some authors have evaluated the expression of COX, especially COX-2, in corneal neoplastic tissues of horses and have suggested a possible role of the enzyme in oncogenesis and/or progression of this type of corneal tumor [23, 24]. The aim of the present study was to describe the clinical and histopathological appearance of a primary corneal SCC in an 8 year-old male pug dog, to report its histopathological findings, and to characterise the tumour using antivimentin and antipan cytokeratin antibodies and evaluate the expression of cyclooxygenase-2, p53 protein, and Ki-67 antigen in the neoplastic cornea by the use
References
[1]
C. A. Fischer, D. M. Lindley, W. C. Carlton, and H. van Hecke, “Tumors of the cornea and sclera,” in Ocular Tumors in Animals and Humans, R. L. Peiffer Jr and K. B. Simons, Eds., pp. 149–202, Blackwell Publishing, Ames, Iowa, USA, 1st edition, 2002.
[2]
B. C. Gilger, E. Bentley, and F. J. Ollivier, “Disease and surgery of the cornea and sclera,” in Veterinary Ophthalmology, K. N. Gelatt, Ed., pp. 690–752, Blackwell Publishing, Ames, Iowa, USA, 4th edition, 2007.
[3]
D. A. Ward, K. S. Latimer, and R. M. Askren, “Squamous cell carcinoma of the corneoscleral limbus in a dog,” Journal of the American Veterinary Medical Association, vol. 200, no. 10, pp. 1503–1506, 1992.
[4]
C. Busse, J. Sansom, R. R. Dubielzig, and A. Hayes, “Corneal squamous cell carcinoma in a Border Collie,” Veterinary Ophthalmology, vol. 11, no. 1, pp. 55–58, 2008.
[5]
K. S. Latimer, R. L. Kaswan, and J. P. Sundberg, “Corneal squamous cell carcinoma in a dog,” Journal of the American Veterinary Medical Association, vol. 190, no. 11, pp. 1430–1432, 1987.
[6]
M. E. Bernays, D. Flemming, and R. L. Peiffer, “Primary corneal papilloma and squamous cell carcinoma associated with pigmentary keratitis in four dogs,” Journal of the American Veterinary Medical Association, vol. 214, no. 2, pp. 215–217, 1999.
[7]
F. Montiani-Ferreira, M. Kiupel, P. Muzolon, and J. Truppel, “Corneal squamous cell carcinoma in a dog: a case report,” Veterinary Ophthalmology, vol. 11, no. 4, pp. 269–272, 2008.
[8]
K. Karasawa, H. Matsuda, and A. Tanaka, “Superficial keratectomy and topical mitomycin C as therapy for a corneal squamous cell carcinoma in a dog: case report,” Journal of Small Animal Practice, vol. 49, no. 4, pp. 208–210, 2008.
[9]
N. Takiyama, E. Terasaki, and M. Uechi, “Corneal squamous cell carcinoma in two dogs,” Veterinary Ophthalmology, vol. 13, no. 4, pp. 266–269, 2010.
[10]
F. S. Prando, F. G. Jannuzzi, M. Rosa, C. G. Lieberknecht, C. F. Lieberknecht, and J. S. Pereira, “Squamous cell carcinoma in the pug cornea-report of two cases (abstract),” Veterinary Ophthalmology, vol. 13, no. 5, p. 408, 2010.
[11]
R. R. Dubielzig, C. S. Schobert, and J. Dreyfus, “Superficial corneal squamous cell carcinoma occurring in dogs with chronic keratitis,” Veterinary Ophthalmology, vol. 14, no. 3, pp. 161–168, 2011.
[12]
O. Gallo, E. Masini, B. Bianchi, L. Bruschini, M. Paglierani, and A. Franchi, “Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma,” Human Pathology, vol. 33, no. 7, pp. 708–714, 2002.
[13]
B. Singh, J. A. Berry, A. Shoher, V. Ramakrishnan, and A. Lucci, “COX-2 overexpression increases motility and invasion of breast cancer cells,” International Journal of Oncology, vol. 26, no. 5, pp. 1393–1399, 2005.
[14]
T. C. Tang, R. T. Poon, C. P. Lau, D. Xie, and S. T. Fan, “Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma,” World Journal of Gastroenterology, vol. 11, no. 13, pp. 1896–1902, 2005.
[15]
R. Miao, N. Liu, Y. Wang et al., “Coexpression of cyclooxygenase-2 and vascular endothelial growth factor in gastrointestinal stromal tumor: possible relations to pathological parameters and clinical behavior,” Hepato-Gastroenterology, vol. 55, no. 88, pp. 2012–2015, 2008.
[16]
J. A. G. Filho, C. F. W. Nonaka, M. C. D. C. Miguel, R. D. A. Freitas, and H. C. Galv？o, “Immunoexpression of cyclooxygenase-2 and p53 in oral squamous cell carcinoma,” American Journal of Otolaryngology, vol. 30, no. 2, pp. 89–94, 2009.
[17]
R. Kawata, S. Hyo, M. Araki, and H. Takenaka, “Expression of cyclooxygenase-2 and microsomal prostagalandin E synthase-1 in head and neck squamous cell carcinoma,” Auris Nasus Larynx, vol. 37, no. 4, pp. 482–487, 2010.
[18]
H. U. Kasper, E. Konze, H. P. Dienes, D. L. Stippel, P. Schirmacher, and M. Kern, “COX-2 expression and effects of COX-2 inhibition in colorectal carcinomas and their liver metastases,” Anticancer Research, vol. 30, no. 6, pp. 2017–2023, 2010.
[19]
K. N. M. Khan, D. W. Knapp, D. B. Denicola, and R. K. Harris, “Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs,” American Journal of Veterinary Research, vol. 61, no. 5, pp. 478–481, 2000.
[20]
K. N. M. Khan, K. M. Stanfield, D. Trajkovic, and D. W. Knapp, “Expression of cyclooxygenase-2 in canine renal cell carcinoma,” Veterinary Pathology, vol. 38, no. 1, pp. 116–119, 2001.
[21]
M. Kleiter, D. E. Malarkey, D. E. Ruslander, and D. E. Thrall, “Expression of cyclooxygenase-2 in canine epithelial nasal tumors,” Veterinary Radiology and Ultrasound, vol. 45, no. 3, pp. 255–260, 2004.
[22]
F. Millanta, S. Citi, D. D. Santa, M. Porciani, and A. Poli, “COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic fmolecular markers,” Breast Cancer Research and Treatment, vol. 98, no. 1, pp. 115–120, 2006.
[23]
C. L. McInnis, E. A. Giuliano, P. J. Johnson, and J. R. Turk, “Immunohistochemical evaluation of cyclooxygenase expression in corneal squamous cell carcinoma in horses,” American Journal of Veterinary Research, vol. 68, no. 2, pp. 165–170, 2007.
[24]
K. M. Rassnick and B. L. Njaa, “Cyclooxygenase-2 immunoreactivity in equine ocular squamous-cell carcinoma,” Journal of Veterinary Diagnostic Investigation, vol. 19, no. 4, pp. 436–439, 2007.
[25]
K. M. Smith, T. J. Scase, J. L. Miller, D. Donaldson, and J. Sansom, “Expression of cyclooxygenase-2 by equine ocular and adnexal squamous cell carcinomas,” Veterinary Ophthalmology, vol. 11, no. 1, pp. 8–14, 2008.
[26]
F. L. Queiroga, I. Pires, L. Lobo, and C. S. Lopes, “The role of Cox-2 expression in the prognosis of dogs with malignant mammary tumours,” Research in Veterinary Science, vol. 88, no. 3, pp. 441–445, 2010.
[27]
E. M. P. de Almeida, C. Piché, J. Sirois, and M. Doré, “Expression of cyclo-oxygenase-2 in naturally occurring squamous cell carcinomas in dogs,” Journal of Histochemistry and Cytochemistry, vol. 49, no. 7, pp. 867–875, 2001.
[28]
F. Millanta, G. Lazzeri, M. Mazzei, I. Vannozzi, and A. Poli, “MIB-1 labeling index in feline dysplastic and neoplastic mammary lesions and its relationship with postsurgical prognosis,” Veterinary Pathology, vol. 39, no. 1, pp. 120–126, 2002.
[29]
V. O. Melnikova, A. Pacifico, S. Chimenti, K. Peris, and H. N. Ananthaswamy, “Fate of UVB-induced p53 mutations in SKH-hr1 mouse skin after discontinuation of irradiation: relationship to skin cancer development,” Oncogene, vol. 24, no. 47, pp. 7055–7063, 2005.
[30]
B. Vojtěsěk, J. Bàrtek, C. A. Midgley, and D. P. Lane, “An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53,” Journal of Immunological Methods, vol. 151, no. 1-2, pp. 237–244, 1992.
[31]
K. Cooper and Z. Haffajee, “bcl-2 and p53 protein expression in follicular lymphoma,” Journal of Pathology, vol. 182, no. 3, pp. 307–310, 1997.
[32]
S. J. Dugan, C. R. Curtis, S. M. Roberts, and G. A. Severin, “Epidemiologic study of ocular/adnexal squamous cell carcinoma in horses,” Journal of the American Veterinary Medical Association, vol. 198, no. 2, pp. 251–256, 1991.
[33]
S. J. Dugan, S. M. Roberts, C. R. Curtis, and G. A. Severin, “Prognostic factors and survival of horses with ocular/adnexal squamous cell carcinoma: 147 cases (1978–1988),” Journal of the American Veterinary Medical Association, vol. 198, no. 2, pp. 298–303, 1991.
[34]
J. P. Teifke and C. V. L？hr, “Immunohistochemical detection of P53 overexpression in paraffin wax-embedded squamous cell carcinomas of cattle, horses, cats and dogs,” Journal of Comparative Pathology, vol. 114, no. 2, pp. 205–210, 1996.
[35]
G. Sironi, P. Riccaboni, L. Mertel, G. Cammarata, and D. E. Brooks, “p53 protein expression in conjunctival squamous cell carcinomas of domestic animals,” Veterinary Ophthalmology, vol. 2, no. 4, pp. 227–231, 1999.
[36]
J. Reszec, M. Sulkowska, M. Koda, L. Kanczuga-Koda, and S. Sulkowski, “Expression of cell proliferation and apoptosis markers in papillomas and cancers of conjunctiva and eyelid,” Annals of the New York Academy of Sciences, vol. 1030, pp. 419–426, 2004.
[37]
J. Gerdes, L. Li, C. Schlueter et al., “Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67,” American Journal of Pathology, vol. 138, no. 4, pp. 867–873, 1991.
[38]
G. Singh-Ranger and K. Mokbel, “The role of cyclooxygenase-2 (COX-2) in breast cancer, and implications of COX-2 inhibition,” European Journal of Surgical Oncology, vol. 28, no. 7, pp. 729–737, 2002.
[39]
C. S. Williams, M. Mann, and R. N. DuBois, “The role of cyclooxygenases in inflammation, cancer, and development,” Oncogene, vol. 18, no. 55, pp. 7908–7916, 1999.
[40]
S. I. Mohammed, D. Dhawan, S. Abraham et al., “Cyclooxygenase inhibitors in urinary bladder cancer: in vitro and in vivo effects,” Molecular Cancer Therapeutics, vol. 5, no. 2, pp. 329–336, 2006.
