Lung lobe torsion in association with a pulmonary papillary carcinoma in a dog.

Lung lobe torsion (LLT) is an uncommon condition in dogs reported to be most commonly idiopathic or secondary to trauma, pleural effusion, lung lobectomy or thoracic neoplasia. Carcinomas are the most common primary lung tumours in dogs, but only a few cases have been reported in association with LLT in veterinary medicine. This case describes an adult male neutered Labrador, which presented with lethargy, weight loss and pleural effusion. Computed tomography (CT), cytology of the lung, thoracocentesis and fluid analysis were performed. CT revealed pleural effusion and torsion of the left cranial lung lobe with no evidence of a pulmonary mass or metastatic disease. Thoracotomy and left cranial lung lobectomy were performed. Intraoperatively there was no macroscopic evidence of pulmonary neoplasia. Histopathology of the lobar tissue confirmed grade 2 pulmonary papillary carcinoma. It is possible that early detection and surgical management might help to prevent the morbidity and mortality associated with LLT. However, as in this case, the underlying cause for the LLT will ultimately determine the patient's prognosis. The final diagnosis of papillary carcinoma in this case, was only made via histopathological assessment of the pulmonary tissue as it was unclear on the advanced imaging and macroscopic intraoperative evaluation of the lungs. This case highlights the importance of considering pulmonary neoplasia as a differential for LLT even in the absence of a macroscopic mass, and therefore the value of performing histopathology on the excised lung tissue.

Characterization of neoplastic cells outlining the cystic space of invasive micropapillary carcinoma of the canine mammary gland.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is a rare malignant breast tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the human breast and canine mammary gland. The importance of the tumor microenvironment in cancer development has gradually been recognized, but little is known about the cell types outlining the cystic space of canine IMPC. This study aimed to characterize the neoplastic cells outlining the cystic space of IMPC. RESULTS: Immunohistochemistry (IHC), immunofluorescence (IF), superresolution and transmission electron microscopy (TEM) were used to assess the cell types in the cystic areas of IMPCs. Cells expressing the mesenchymal markers alpha-smooth muscle actin (αSMA), Vimentin, and S100A4 outlined the cystic space of IMPC. Furthermore, loss of epithelial cell polarity in IMPC was shown by the localization of MUC1 at the stroma-facing surface. This protein modulates lumen formation and inhibits the cell-stroma interaction. Immunohistochemical and IF staining for the myoepithelial cell marker p63 were negative in IMPC samples. Furthermore, associated with peculiar morphology, such as thin cytoplasmic extensions outlining cystic spaces, was observed under TEM. These observations suggested cells with characteristics of myoepithelial-like cells. CONCLUSIONS: The cells outlining the cystic space of IMPC in the canine mammary gland were characterized using IHC, IF and TEM. The presence of cells expressing αSMA, Vimentin, and S100A4 in the IMPC stroma suggested a role for tumor-associated fibroblasts in the IMPC microenvironment. The reversal of cell polarity revealed by the limited basal localization of MUC1 may be an important factor contributing to the invasiveness of IMPC. For the first time, the cystic space of canine mammary gland IMPC was shown to be delimited by myoepithelial-like cells that had lost p63 expression. These findings may enhance our understanding of the cellular microenvironment of invasive tumors to improve cancer diagnosis and treatment.

The outcome for feline non-hypersecretory thyroid carcinoma after thyroidectomy.

A 14-year-old neutered male cat was presented because of a left ventral cervical mass. Based on imaging, the mass was suspected to have a thyroid origin. There was no evidence of gross metastatic disease or hyperthyroidism. Left thyroidectomy alone was the treatment for this patient and a thyroid carcinoma was diagnosed on histopathology. At last follow-up, 831 days after surgery, there was suspicion of metastasis to the lungs and the cat had developed a right thyroid mass and hyperthyroidism. Key clinical message: This case report identifies a non-hypersecretory thyroid carcinoma. This is a rare diagnosis. The outcome with surgery alone was comparable to that reported for treatment with iodine131.

Issue à la suite d'une thyroïdectomie pour un carcinome thyroïdien non-hypersecréteur félin. Un chat mâle castré âgé de 14 ans fut présenté concernant une masse ventro-cervicale gauche. Basé sur l'imagerie, la masse était suspectée être d'origine thyroïdienne. Il n'y avait pas d'évidence macroscopique de métastases ou d'hyperthyroïdisme. Une thyroïdectomie gauche fut l'unique traitement pour ce patient et un carcinome thyroïdien fut diagnostiqué lors de l'examen histopathologique. Lors de la dernière visite de suivi, 831 jours après la chirurgie, il y avait un doute de métastases aux poumons et le chat avait développé une masse thyroïdienne droite et de l'hyperthyroïdisme.Message clinique clé :Ce rapport de cas identifie un carcinome thyroïdien non-hypersecrétoire. Il s'agit d'une condition rarement diagnostiquée. L'issue à la suite de seulement une chirurgie était comparable à ce qui est rapporté pour un traitement avec de l'iode131.(Traduit par Dr Serge Messier).

Bovine papillomavirus E5 oncoprotein upregulates parkin-dependent mitophagy in urothelial cells of cattle with spontaneous papillomavirus infection: A mechanistic study.

This study aimed to provide mechanistic insights into mitophagy pathway associated with papillomavirus infection in urothelial cells of cattle. The elimination of mitochondria via autophagy, termed mitophagy, is an evolutionarily conserved mechanism for mitochondrial quality control and homeostasis. PINK1/parkin-mediated mitophagy, a ubiquitin-dependent selective autophagy of dysfunctional mitochondria, has been described here, for the first time, in urothelial cells from 25 bladder cancers in cattle infected by bovine papillomavirus (BPV). The expression of BPV-2 and BPV-13 E5 oncoprotein was detected by RT-PCR. Abnormal mitochondria delimited by expanding phagophores, were peculiar ultrastructural features of neoplastic urothelial cells. High levels of mitochondrial phosphorylated PINK1/parkin were observed in neoplastic urothelial cells infected by BPVs. Phosphoparkin interacted with mitofusin 2 (Mfn2) and ubiquitin (Ub), which confirmed that Mfn2 is a parkin receptor at the mitochondrial level, where parkin interacted also with Ub. Furthermore, parkin established a complex that was comprised of optineurin, p62, LC3, laforin, and embryonic stem cell-expressed Ras (ERAS), that interacted with BPV E5 oncoprotein, and Bag3, which, in turn, regulated the formation of a complex composed of Hpc70/Hsp70, CHIP, an HSC70-interacting E3 ubiquitin ligase. It is conceivable that ERAS is involved in mitophagosome maturation via phosphatidylinositol 3-kinase (PI3K) pathway. Bag3, in association with Hsc70/Hsp70, may contribute to the transport and degradation of CHIP-ubiquitinated cargo as this complex recognises ubiquitinated cargos and transports them to aggresomes to be degraded. Furthermore, Bag3 may be involved in mitophagosome formation as it interacted with synaptopodin 2, which is known to play a role in mitophagosome biogenesis.

The investigation of transcriptional repression mediated by ZEB2 in canine invasive micropapillary carcinoma in mammary gland.

The E-cadherin loss has frequently been associated with transcriptional repression mediated by transcription factors, such as the Zinc Finger E-Box Binding Homeobox-2 (ZEB2). Invasive micropapillary carcinomas (IMPCs) of the breast are aggressive neoplasms frequently related to lymph node metastasis and poor overall survival. In the canine mammary gland, IMPCs has just been reported and, based on its behavioral similarity with the human IMPCs, appears to be a good spontaneous model to this human entity. This study aimed to evaluate the relationship between E-cadherin and ZEB2 in a spontaneous canine model of invasive micropapillary carcinoma of the mammary gland. The correlation among gene expression (ZEB2 and CDH1) and clinicopathological findings was also explored. Nineteen cases of IMPC of the canine mammary gland were obtained, protein and mRNA expression were investigated through immunohistochemistry and RNA In Situ Hybridization, respectively. To better understand the relationship between E-cadherin and ZEB2, immunofluorescence was performed in canine IMPCs. Immunohistochemically, most of IMPCs showed 1+ (14/19, 73.7%) for E-cadherin; and positivity for ZEB2 was diagnosed in 47.4% of the IMPCs. Regarding the RNA In Situ Hybridization (ISH), most of IMPCs showed 4+ and 0+ for E-cadherin (CDH1) and ZEB2 respectively. Through immunofluorescence, the first and second more frequent combinatorial group were E-cadherin+ZEB2- and E-cadherin+ZEB2+; neoplastic cells showing concomitantly weak expression for E-cadherin and positivity for ZEB2 were frequently observed. A negative correlation was observed between E-cadherin and progesterone receptor expression in IMPCs. Based on these results, canine mammary IMPCs show E-cadherin lost and, at times reveals nuclear positivity for the transcription factor ZEB2 that seems to exert transcriptional repression of the CDH1.

Invasive micropapillary carcinoma of the mammary gland in humans and canines: Clinicopathological, immunophenotypical and survival approaches.

Invasive micropapillary carcinoma (IMPC) is a breast cancer with a proclivity for lymph node metastasis that affects women. In canines, this carcinoma has only recently been reported and appears to have similar histological aspects as its human counterpart. Thus, the aim of the present study was to compare clinicopathological, immunohistochemical and prognostic characteristics of mammary IMPC between humans and canines. In canines, regional metastasis was more frequently observed. Histopathologically, humans and canines predominantly showed a moderate histological grade. The pure subtype and neoplastic emboli were more frequently observed in canines. Regarding immunohistochemical evaluation, most canine and human IMPCs were positive for the estrogen and progesterone receptors. A reversed pattern of epithelial membrane antigen expression and a high proliferation index predominated in both species. The mortality due to the neoplastic disease was more frequently observed in canines (94%) than in humans (4%). Thus, canine IMPCs show a larger tumor size and higher rates of the pure subtype, regional metastasis and mortality than their human counterparts and appear to provide a good spontaneous model for achieving a better understanding of the biological behavior of human IMPCs.

Treatment of a giant pulmonary emphysematous cyst with primary bronchoalveolar papillary carcinoma in a Shih Tzu dog.

OBJECTIVE: To report the surgical treatment of a pulmonary emphysematous cyst concurrent with primary pulmonary bronchoalveolar papillary carcinoma in a dog. STUDY DESIGN: Clinical case report. ANIMALS: 12-year-old 6.4 kg spayed female Shih Tzu dog. METHODS: The dog presented for surgical treatment of pulmonary emphysema. Radiography revealed that more than half of the left caudal lung lobe was enlarged and hyperlucent and computed tomography (CT) confirmed the presence of an emphysematous space. Thoracoscopic lung lobectomy was attempted but was converted to an intercostal thoracotomy due to poor visualization and pleural adhesions. A left caudal total lung lobectomy was performed using a self-cutting endoscopic stapler. RESULTS: The dog recovered uneventfully and a postoperative histopathologic diagnosis of pulmonary cystic bronchoalveolar papillary carcinoma was made. Re-evaluation using a CT scan with contrast study on postoperative days 27 and 177 revealed no evidence of residual, metastatic, or recurrent lesions. The dog has been doing well since surgery during the 11 month follow-up period. CONCLUSION: This case report suggests a potential relationship between pulmonary emphysematous diseases and primary lung tumors in dogs.

Inner nuclear membrane localization of epidermal growth factor receptor (EGFR) in spontaneous canine model of invasive micropapillary carcinoma of the mammary gland.

The epidermal growth factor receptor (EGFR) has been described in the nucleus of primary tumors. Accumulation of EGFR at the nucleus is linked to DNA synthesis and cell proliferation, but the pathological significance of nuclear EGFR is not completely understood. The aim of this study was to investigate the nuclear localization of EGFR in invasive micropapillary carcinoma (IMPC) that is an aggressive neoplasm of canine mammary gland. Confocal immunofluorescence of formalin and paraffin-embedded tissue was used to access the subcellular localization of EGFR. Our results demonstrated that EGFR co-localizes with the inner nuclear envelope marker, Lamin B1 in IMPC. Furthermore, EGFR was not localized within the nucleus or at the inner nuclear envelope membrane in mammary carcinoma in mixed tumor (CMT) that is associated with a better prognosis than other malignant histological types. This finding could be useful as a predictive biomarker of therapeutic response for IMPC.

St Gallen molecular subtypes in feline mammary carcinoma and paired metastases-disease progression and clinical implications from a 3-year follow-up study.

Considering that scarce data are available on disease progression of feline mammary carcinoma (FMC), this study aimed to analyze the clinical, pathological, and immunophenotypic features collected from 61 queens with FMC and to compare the concordance ratios of the expression levels of five molecular markers (ER, PR, fHER2, CK5/6, and Ki-67) between primary tumors (PT) and metastatic lesions. The results showed that cats with luminal A mammary carcinomas (MC) had higher overall survival (924.6 days, p = 0.001) and longer disease-free period (385.4 days, p = 0.005) compared to the ones with other MC subtypes. In fact, queens with triple negative/basal-like MC showed the lowest survival (mean 156.2 days) and the shortest disease-free survival (mean 28 days) among the molecular subtypes of MC. The lung was the organ most frequently affected by metastases, and animals with lung and/or pleural metastases were more likely to display metastases at three or more locations (p = 0.039). A large heterogeneity in protein expression levels was found between PT and paired metastases, with both estrogen and progesterone receptors more likely to be downregulated in metastases. Paired metastases frequently had higher Ki-67 index than PT, whereas fHER2 overexpression was seen in 46 samples (30 %) and CK5/6 expression was found in 50.7 % of metastases (36/71). Results also revealed that disease progression leads to a high percentage of triple negative/basal-like metastases (9/23; 39.1 %) associated with the absence of luminal A subtype in distant metastases (0/23). This study highlights the prognostic importance of immunophenotyping of MC in cats, although the modified protein expression identified in metastases contributes to justify why possible targeted therapies may fail in some animals with metastatic disease. Altogether, the results obtained also demonstrate that FMC can be used as a model to study human breast cancer.

The Relationship Between E-Cadherin and its Transcriptional Repressors in Spontaneously Arising Canine Invasive Micropapillary Mammary Carcinoma.

E-cadherin downregulation is related to metastatic behaviour and a poor prognosis in cancer. It might be induced by transcriptional repression mediated by the transcription factors SNAIL, ZEB1, ZEB2 and TWIST. Here, we investigated E-cadherin expression and its relationship to those transcriptional repressors (i.e. SNAIL, ZEB1, ZEB2 and TWIST) in the progression from carcinoma 'in situ' to invasion to lymph node metastasis in spontaneously arising canine invasive micropapillary carcinoma (IMPC). E-cadherin expression decreased from carcinoma in situ to invasive progression and was likely to increase with lymph node metastasis. Expression of SNAIL decreased from carcinoma in situ to invasive areas and from invasive areas to lymph nodes. Metastatic lymph nodes had higher expression of ZEB1 than carcinoma in situ and invasive areas. ZEB2 expression was observed in 52%, 38% and 33% of carcinoma in situ areas, invasive areas and lymph node metastases, respectively. TWIST expression was observed in 52%, 38% and 33% of carcinoma in situ areas, invasive areas and lymph node metastases, respectively. In invasive areas, E-cadherin downregulation correlated significantly with SNAIL and TWIST upregulation. Additionally, in infiltrating components of IMPCs, E-cadherin(-)SNAIL(+) neoplastic epithelial cells were observed by immunofluorescence. Taken together, canine mammary IMPCs had a loss of E-cadherin from carcinoma in situ to invasive areas, which appears to be induced by the transcription factor SNAIL. In lymph node metastasis, ZEB1 appears to not exert E-cadherin transcriptional repression activity.

Cytologic analysis of the mammary papillar discharge in a canine micropapillary carcinoma.

This is a report on the cytologic analysis of the mammary papillar discharge in a 7-year-old female Doberman dog with an invasive micropapillary carcinoma. Cytologic evaluation of nipple discharge is a well-known method for the rapid diagnosis of breast cancer in women. However, there is no previous report regarding the use of this technique for assessing mammary tumors in dogs. The aim of this study was to describe the use of mammary papillar discharge cytology for diagnosing a micropapillary carcinoma in a dog. Cytologically, evaluation of the papillar discharge revealed cells arranged in clusters in a papillary pattern or in a morula-like arrangement, suggesting the diagnosis of a micropapillary carcinoma, which was subsequently confirmed by histopathology. Thus, mammary papillar discharge cytology should be considered as an ancillary method for evaluating mammary diseases in dogs.

ARFI elastography as a complementary diagnostic method for mammary neoplasia in female dogs - preliminary results.

OBJECTIVES: To evaluate the applicability of acoustic radiation force impulse elastography as a complementary method in diagnosing mammary neoplasia in dogs. METHODS: Mammary tumours from 50 female dogs were evaluated and divided into two groups: G1 (benign tissue) and G2 (malignant tumours). The nodules were assessed by B-Mode ultrasonography, qualitative and quantitative acoustic radiation force impulse elastography and histopathology. RESULTS: B-Mode ultrasound examination was ineffective at separating the tumours into the two groups. Likewise, there was no correlation between the grayscale images of the mammary tissue by qualitative elastography. A difference was found in the deformity of the mammary masses between the malignant and benign groups (P = 0 · 002). Using quantitative elastography, the mean values of shear velocity were 3 · 33 m/s for malignant tumours and 1 · 28 m/s for benign tissue (P < 0 · 0001). CLINICAL SIGNIFICANCE: The use of acoustic radiation force impulse elastography may help to differentiate between malignant and benign mammary neoplasms.

Outcome and prognostic indicators in 20 cats with surgically treated primary lung tumors.

The purpose of this retrospective study of 20 client-owned cats was to describe the clinical signs, surgical interventions, histological features, stage and treatments of primary lung tumors removed by surgical excision, and to determine which factors significantly influence survival. Any cat that underwent surgical resection of a primary lung tumor between 2000 and 2007 was included in the study. Patient records were reviewed and signalment, clinical signs, preoperative diagnostics, surgical findings and histopathological results recorded. Histological reports were reviewed and scored using World Health Organization criteria. The Kaplan-Meier test was used to evaluate each potential prognostic factor with survival. Twenty cats met the inclusion criteria. The presence of clinical signs (such as dyspnea) at the time of diagnosis (P = 0.032), pleural effusion (P = 0.046), stage M1 (P = 0.015), and moderately and poorly differentiated tumors on histopathology (P = 0.011) were factors that were significantly correlated with reduced survival times. The median survival time of the 20 cats was 11 days. Cats presenting with no clinical signs had a median survival time of 578 days post-surgery vs 4 days post-surgery when presented with clinical signs. Cats staged T1N0M0 lived longer than cats at other stages (P = 0.044). Of the cats that survived to the time of suture removal, median survival time was 64 days. The results indicate that the presence of clinical signs, pleural effusion, moderately and poorly differentiated tumors on histopathology, evidence of metastasis and any stage beyond T1N0M0 are negative prognostic indicators for cats with primary lung tumors. The findings demonstrate that cats that presented with clinical signs, pleural effusion, any stage other than T1N0M0, or moderately and poorly differentiated tumors on histopathology had a poor prognosis. Therefore, extensive preoperative diagnostics, including computed tomography scans, should be performed before considering surgical intervention in these cats. These findings may be used to guide therapeutic decision-making in cats diagnosed with primary lung tumors.

Oral papillary squamous cell carcinoma in twelve dogs.

Papillary squamous cell carcinoma (PSCC) is a distinct histological subtype of oral squamous cell carcinoma (SCC), described in both dogs and man. In dogs, PSCC has long been considered a malignant oral tumour of very young animals, but it has recently been reported to occur in adult dogs as well. The aim of this study was to describe the major clinicopathological characteristics of canine oral PSCC (COPSCC). Twelve dogs diagnosed with COPSCC were included in this retrospective study (1990-2012). The majority (75%) of the dogs were >6 years of age (median age 9 years). All tumours were derived from the gingiva of dentate jaws, with 66.7% affecting the rostral aspects of the jaws. The gross appearance of the lesions varied, with one having an intraosseous component only. The majority (91.7%) of the tumours were advanced lesions (T2 and T3), but no local or distant metastases were noted. Microscopically, two patterns were seen: (1) invasion of bone forming a cup-shaped indentation in the bone or a deeply cavitating cyst within the bone (cavitating pattern), (2) histologically malignant growth, but lack of apparent bone invasion (non-cavitating pattern). The microscopical appearance corresponded to imaging findings in a majority of cases, with cavitating forms presenting with a cyst-like pattern of bone loss or an expansile mass on imaging and non-cavitating forms showing an infiltrative pattern of bone destruction on imaging. These features suggest two distinct biological behaviours of COPSCC.

Clinical, cytologic, and histologic features of a mammary micropapillary carcinoma in a dog.

Mammary invasive micropapillary carcinoma is a rare variant of mammary carcinoma that was recently recognized in dogs. The cytologic features and biologic behavior of such neoplasms in dogs have not yet been widely discussed in the veterinary literature. We report the clinical, cytologic, and histologic features of a canine micropapillary carcinoma in a 13-year-old female mongrel dog. The mammary region presented with extreme local pain, severe edema and erythema, and multifocal epidermal ulceration, which is typical for an inflammatory mammary carcinoma. Fine-needle aspirates were highly cellular and consisted of individual cells and papillary cell clusters with characteristics of malignant epithelial cells. Histologic examination revealed neoplastic cells arranged in small papillae without fibrovascular cores, sometimes inside clear lymphatic spaces, indicating lymphovascular invasion. Regional lymph node evaluation revealed metastatic cells. Due to deteriorating clinical condition the dog was euthanatized 5 months after mastectomy. At necropsy, metastatic neoplastic mammary cells were found in popliteal and mediastinal lymph nodes, the right femoral biceps muscle, liver, heart, lungs, and urinary bladder.

Productive infection of bovine papillomavirus type 2 in the placenta of pregnant cows affected with urinary bladder tumors.

Papillomaviruses (PVs) are believed to be highly epitheliotropic as they usually establish productive infections within stratified epithelia. In vitro, various PVs appear to complete their entire life-cycle in different trophoblastic cell lines. In this study, infection by and protein expression of bovine papillomavirus type 2 (BPV-2) in the uterine and chorionic epithelium of the placenta has been described in four cows suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected both by Western blot analysis and immunohistochemically. It appears to be complexed and perfectly co-localized with the activated platelet-derived growth factor ß receptor (PDGFßR) by laser scanning confocal microscopy. The activated PDGFßR might be involved in organogenesis and neo-angiogenesis rather than in cell transformation during pregnancy. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection has been detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the uterine and chorionic epithelium. Trophoblastic cells appear to be the major target for L1 protein expression. Finally, the early protein E2, required for viral DNA replication and known to be expressed during a productive infection, has been detected by Western blot and immunohistochemically. Electron microscopic investigations detected viral particles in nuclei of uterine and chorionic epithelium. This study shows that both active and productive infections by BPV-2 in the placenta of pregnant cows can occur in vivo.

Tetrathyridiosis and tubulopapillary carcinoma occurring simultaneously in the mammary gland of a cat.

This report describes a case of tubulopapillary carcinoma and concomitant tetrathyridiosis in a 5-year-old female cross-breed cat. A mass was located at right inguinal mammary gland and measured 5.5 × 5 × 3 cm in size with multilobulated to solid appearance. The cut surface of the mass had a centrally located large cyst (approximately 3 cm in diameter) surrounded by other smaller cysts. Histologically, the mass was diagnosed as tubulopapillary mammary carcinoma, intensely positive for AE1/AE3 cytokeratins. The cyst found at post-mortem examination was tetrathyridia of Mesocestoides species surrounded by inflammatory cells and a loose fibrous capsule. To the authors' best knowledge, this is the first description of a tubulopapillary carcinoma and tetrathyridiosis found simultaneously in the mammary gland of a cat.

COX-2 expression and outcome in canine nasal carcinomas treated with hypofractionated radiotherapy.

The expression of cyclooxygenase isoform 2 (COX-2) in canine nasal carcinomas has been well documented. COX-2 expression has proven to be a prognostic factor in several human tumours. The aims of this study were to assess the correlation between immunohistochemical COX-2 expression and prognosis using rhinoscopic biopsies from 42 dogs with nasal carcinomas treated with hypofractionated radiotherapy, and to establish a replicable COX-2 scoring system. Ninety per cent of sections evaluated were COX-2 positive with a mean score of 6.6 (median 8.0; range 0-12). Neither COX-2 expression nor tumour type had a significant correlation with survival. There are likely to be many as yet unidentified variants which contribute to length of survival in dogs with nasal carcinomas. Immunohistochemical COX-2 expression appears unlikely to be of prognostic significance for canine nasal carcinoma.