Estrogen Receptor and Signal Transducer and Activator of Transcription 3 Expression in Equine Mammary Tumors.

Equine mammary tumors are uncommon, and relatively sparse histopathologic and molecular data exist. The present study describes the histopathologic features of 7 such tumors, which exhibited infiltrative growth, intermediate to high mitotic rates, and focally extensive necrosis. The tumors exhibited variably strong staining for vimentin and cytokeratin 14, as well as frequently weak cytoplasmic staining for pan-cytokeratin. E-cadherin expression was strong. Interestingly, a subgroup of the tumors exhibited strong nuclear staining for estrogen receptor α. Three of 7 tumors exhibited nuclear expression of the transcription factor STAT3, suggesting that STAT3 was transcriptionally active. Rare to absent nuclear STAT3 expression was observed in carcinomas exhibiting moderate to intense staining for cytokeratin 14. This investigation confirms previous investigators' assertions that equine mammary tumors have a malignant phenotype. A subset of the equine mammary tumors exhibited estrogen receptor α expression, suggesting that these tumors may potentially have similar molecular characteristics to their feline and canine counterparts.

Classification of canine malignant lymphomas according to the World Health Organization criteria.

A study was carried out to test the accuracy and consistency of veterinary pathologists, not specialists in hematopathology, in applying the World Health Organization (WHO) system of classification of canine lymphomas. This study represents an initiative of the ACVP Oncology Committee, and the classification has been endorsed by the World Small Animal Veterinary Association (WASVA). Tissue biopsies from cases of canine lymphoma were received from veterinary oncologists, and a study by pathologists given only signalment was carried out on 300 cases. Twenty pathologists reviewed these 300 cases with each required to choose a diagnosis from a list of 43 B and T cell lymphomas. Three of the 20 were hematopathologists who determined the consensus diagnosis for each case. The 17 who formed the test group were experienced but not specialists in hematopathology, and most were diplomates of the American or European Colleges of Veterinary Pathology. The overall accuracy of the 17 pathologists on the 300 cases was 83%. When the analysis was limited to the 6 most common diagnoses, containing 80% of all cases, accuracy rose to 87%. In a test of reproducibility enabled by reintroducing 5% of cases entered under a different identity, the overall agreement between the first and second diagnosis ranged from 40 to 87%. The statistical review included 43,000 data points for each of the 20 pathologists.

Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior.

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.

Recommended guidelines for submission, trimming, margin evaluation, and reporting of tumor biopsy specimens in veterinary surgical pathology.

Neoplastic diseases are typically diagnosed by biopsy and histopathological evaluation. The pathology report is key in determining prognosis, therapeutic decisions, and overall case management and therefore requires diagnostic accuracy, completeness, and clarity. Successful management relies on collaboration between clinical veterinarians, oncologists, and pathologists. To date there has been no standardized approach or guideline for the submission, trimming, margin evaluation, or reporting of neoplastic biopsy specimens in veterinary medicine. To address this issue, a committee consisting of veterinary pathologists and oncologists was established under the auspices of the American College of Veterinary Pathologists Oncology Committee. These consensus guidelines were subsequently reviewed and endorsed by a large international group of veterinary pathologists. These recommended guidelines are not mandated but rather exist to help clinicians and veterinary pathologists optimally handle neoplastic biopsy samples. Many of these guidelines represent the collective experience of the committee members and consensus group when assessing neoplastic lesions from veterinary patients but have not met the rigors of definitive scientific study and investigation. These questions of technique, analysis, and evaluation should be put through formal scrutiny in rigorous clinical studies in the near future so that more definitive guidelines can be derived.

Recommended guidelines for the conduct and evaluation of prognostic studies in veterinary oncology.

There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.

Histopathological frequency of canine hepatobiliary disease in the United Kingdom.

OBJECTIVES: Canine hepatobiliary disease is common; however, data determining disease frequency and breed predispositions are lacking. The primary objective was to identify the frequency of different hepatobiliary disease in a United Kingdom population of dogs and consequently determine breeds at both an increased and decreased risk of hepatobiliary disease. MATERIALS AND METHODS: Anonymised histopathology reports from a commercial veterinary diagnostic laboratory, which were submitted between August 2013 and February 2018, were analysed. Data were retrospectively categorised into hepatobiliary diseases according to World Small Animal Veterinary Association Standards and the breed, age and genders recorded. Cases with incomplete data or no definitive diagnosis were excluded. Breed predisposition was calculated using odds ratios and 95% confidence intervals against a United Kingdom-based control population of micro-chipped dogs. RESULTS: Histopathology results from 4584 cases met inclusion criteria. The most frequent histological diagnoses were reactive hepatitis (n=770); chronic hepatitis (n=735) and reversible hepatocellular injury (n=589). A number of breeds were shown to be at an increased or decreased risk of individual liver diseases. CLINICAL SIGNIFICANCE: This is the first study to document the histopathological frequency of hepatobiliary diseases in a large cohort of dogs in the United Kingdom, as well as novel possible breed and age predispositions. Despite multivariable analysis not being performed to account for confounding factors, this information hopes to inform and support future investigations for hepatic disease in particular breeds and potential predispositions.

Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

In Salmonella enterica serovar Typhimurium, trxA encodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was partially attributed to a reduction in the number of both CD4(+) and CD8(+) T cells and B lymphocytes in the spleen and reduced infiltration by CD11b(+) cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.

Equus caballus papillomavirus-2 (EcPV-2): an infectious cause for equine genital cancer?

REASONS FOR PERFORMING STUDY: The aetiology of genital squamous cell carcinoma (SCC) in horses remains unknown, but the similarity to the disease in man, for which papillomavirus infection has been shown to be a causal factor, requires to be investigated in horses. HYPOTHESIS: One or more novel papillomaviruses cause equine genital SCC and its associated premalignant lesions. METHODS: DNA was extracted from samples of equine genital SCC and performed rolling circle amplification, in order to identify closed circular DNA viral genomes within the samples. The amplified DNA was subcloned and sequenced and the DNA sequence compared to that of other papillomavirus genomes. Using PCR primers developed from these genomic DNA sequences, studies were then carried out in order to identify the frequency at which the viral DNA could be identified in equine genital cancer samples from horses in both the UK, Australia and Austria. Finally, in situ hybridisation using specific probes developed from this DNA sequence were used to confirm the presence of the viral RNA sequences in the neoplastic cells in these lesions. RESULTS: The full length genome of a novel papillomavirus species was characterised from the equine genital SCC tissue and termed Equus caballus papillomavirus-2 (EcPV-2). Viral DNA and RNA was identified in the genital tumour samples, but not in the adjacent histologically normal tissue. EcPV-2 DNA could not be identified in equine ocular or nasal carcinomas or within the scrotal skin or in most smegma samples obtained from tumour-free horses. Sequencing of amplicons, generated from the archived equine genital tumours, identified variations within E1 and E6 on DNA and predicted protein level. CONCLUSIONS: A novel papillomavirus, EcPV-2, is likely to play a causal role in the pathogenesis of equine genital epithelial tumours. POTENTIAL RELEVANCE: Identification of a papillomavirus causal for genital carcinomas in horses may lead to development of a vaccine that could be used to prevent this serious disease in horses. This would be analogous to man, where vaccination against oncogenic papillomavirus species is currently being used to help prevent cervical cancer.

Chronic Inflammatory Disease in the Pancreas, Kidney and Salivary Glands of English Cocker Spaniels and Dogs of Other Breeds Shows Similar Histological Features to Human IgG4-related Disease.

Chronic pancreatitis (CP) is a common disease in the English cocker spaniel (ECS) and is characterized histologically by duct destruction, interlobular fibrosis and dense periductular and perivenous lymphocytic aggregates. These features are also found in human autoimmune pancreatitis type 1, part of a glucocorticoid-responsive, multiorgan syndrome, newly recognized as IgG4-related disease (IgG4-RD). Human IgG4-RD affects one or several organs, often showing a predominance of IgG4+ plasma cells histologically, with an IgG4+:total IgG+ plasma cell ratio of >40%. This study investigated whether ECSs with CP and/or inflammatory disease in several organs show an increase in IgG4+ plasma cells within affected tissues. Histological sections of pancreas, liver, kidney, salivary gland and conjunctiva were obtained from ECSs with idiopathic chronic inflammatory disease affecting those tissues. Tissue samples from age-matched dogs of other breeds with similar diseases were also sampled. Control diseased tissue samples, from dogs without a suspected immune-mediated disease, were included. A subset of ECSs and dogs of other breeds presented with disease in more than one organ. Immunohistochemistry was performed with primary reagents detecting total IgG and three of the four canine IgG subclasses (IgG2, IgG3 and IgG4). Normal sections of pancreas and liver showed an absence of labelled plasma cells of any subclass. Normal kidney and salivary gland sections showed the presence of a few labelled plasma cells (<10 plasma cells/high-power field). Fourteen tissue sections from 12 ECSs and seven sections from six dogs of other breeds showed elevated numbers of IgG4+ plasma cells and IgG4+:IgG+ ratios >40%. Individual dogs (ECSs and other breeds) showed marked increases in IgG4+ cells. There were no significant differences in the number of IgG4+ plasma cells between ECSs and dogs of other breeds for affected pancreas, liver, salivary glands and conjunctiva. Kidney sections had more IgG4+ cells, for both ECSs and dogs of other breeds, than did sections from other organs. Dogs of other breeds had significantly more IgG4+ plasma cells in affected kidneys than ECSs. In conclusion, several ECSs and dogs of other breeds fulfilled the histological criteria for the diagnosis of IgG4-RD, supporting the existence of a multiorgan immune-mediated disease in ECSs and some dogs of other breeds.

Ascites is a negative prognostic indicator in chronic hepatitis in dogs.

BACKGROUND: Chronic hepatitis (CH) in dogs is common but little is known about factors associated with survival. Ascites is a well-recognized negative prognostic indicator in humans. HYPOTHESIS: Ascites is a negative prognostic indicator in CH in dogs. ANIMALS: Thirty-four dogs with histologically confirmed CH presented to 1 institution between 1996 and 2005. METHODS: Retrospective observational study. CH was diagnosed by histopathology of liver tissue according to the WSAVA criteria. Ascites was diagnosed by abdominal ultrasound. The association of ascites with survival from diagnosis or onset of owner-reported clinical signs until death from any cause or from liver disease was analyzed. Ascitic and nonascitic groups were further analyzed for differences in treatment and sex. RESULTS: Fourteen of 34 dogs had ascites. Survival from diagnosis to death from liver disease was 0.4 months (95% confidence interval [CI], 0.2-0.6) for ascitic dogs and 24.3 months (CI 11.4-37.1) for nonascitic dogs (P < .001), and from onset of signs to death from liver disease was 2.0 months (CI 0.0-5.6) for ascitic dogs and 33.0 months (CI 8.6-57.4) for nonascitic dogs (P= .0020). Diet and spironolactone use differed between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Ascites is a significant negative prognostic indicator in dogs with CH. Veterinarians and owners can use this information to aid clinical decision making in affected dogs.

Ki-67 and vascular endothelial growth factor expression in intracranial meningiomas in dogs.

BACKGROUND: Tumor proliferation in human intracranial meningiomas can be defined by the reactivity of the monoclonal antibody MIB-1 to the Ki-67 antigen. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is a predictive marker for survival of dogs with intracranial meningiomas. HYPOTHESIS: Ki-67 is expressed in canine intracranial meningiomas and is associated with VEGF expression. Ki-67 expression is a prognostic marker for patient outcome. ANIMALS: Seventy client-owned dogs with WHO grade I intracranial meningiomas. METHODS: Retrospective study assessing the degree of immunostaining for Ki-67 by MIB-1 and VEGF expression in intracranial meningioma tissue from dogs. MIB-1 Labeling Index (LI) was calculated with Image J NIH-software. Extent, intensity, and distribution of VEGF-expression was assessed semiquantitatively. Cross tabulations with Fisher's exact tests and nonparametric Spearman's rank correlations were performed to identify associations between VEGF expression and MIB-1 LI. Fifteen dogs underwent postsurgical radiotherapy and were included in survival analysis. The effect of MIB-1 LI on survival was examined by Kaplan-Meier and Cox proportional hazards regression procedures. RESULTS: Ki-67 staining was positive in 91% (64/70) and VEGF expression was detected in 96% (67/70). There was no significant association between VEGF expression and MIB-1 LI. MIB-1 LI was not associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: MIB-1 antibody can be used to document cell proliferation in intracranial meningiomas in dogs, but does not predict outcome. No association between VEGF as a marker of angiogenesis and tumor proliferation was found. Angiogenesis might be a more important predictor of meningioma activity in dogs than is Ki-67.

A Fibromyxoid Stromal Response is Associated with Muscle Invasion in Canine Urothelial Carcinoma.

Canine urothelial carcinoma (UC) is the most common type of cancer of the lower urinary tract and tends to affect elderly neutered female dogs, with a high predisposition for Scottish terriers. Tumour stroma, inflammation and necrosis are poorly characterized in canine UC and their role as prognostic factors is unknown. The aims of this study were to (1) assess histologically 381 canine UCs, with emphasis on myxoid tumour stroma, inflammation and necrosis and (2) assess possible associations between these features and the available epidemiological data as well as bladder wall muscle invasion. In 103 of 381 (27%) cases, the stroma was mixed collagenous and myxoid (fibromyxoid), which was strongly associated with invasive growth of muscle (P <0.0001). Peritumoural and intratumoural inflammation was present in 308 of 345 (89%) and 287 of 381 (75%) cases, respectively, and was mostly mild and lymphoplasmacytic. One hundred and fifteen of the 381 (30%) cases showed a variable eosinophilic inflammation and 58 of 381 (15%) presented with formations of one or several lymphoid follicles. Twenty-four percent (91 of 381) of cases had tumour necrosis, which was typically mild. In 83 of 91 (91%) cases, the necrosis was comedo-like. Moderate to severe tumour necrosis was associated with the presence of moderate to predominant fibromyxoid tumour stroma (P <0.02). The results of this study indicate that fibromyxoid stroma is common in canine UC and is a strong indicator for invasive growth of muscle, which is consistent with a poor prognosis. Based on histomorphology, tumour necrosis in canine UC is best described as comedonecrosis.

Leiomyosarcoma of the pericardium, with epicardial metastases and peripheral eosinophilia in a dog.

A dog with a history of dyspnoea, anorexia and ascites showed on examination signs of right-sided heart failure, pleural effusion and peripheral eosinophilia. Diagnostic imaging suggested the presence of a mediastinal mass, and histopathological and immunohistochemical examination of a biopsy sample led to a diagnosis of leiomyosarcoma. On post-mortem examination, an extensive mass was found, which encircled the heart and obliterated the pericardial sac, with probable metastatic spread to the epicardium. Eosinophilic infiltration of the neoplastic mass, lamina propria of the stomach and duodenum, interstitium of the kidney, and submucosa of the bladder was consistent with a possible paraneoplastic eosinophilia.

Congenital hyposomatotropism in a domestic shorthair cat presenting with congenital corneal oedema.

A six-month-old, female, domestic shorthair cat was presented with a history of failure to grow and bilateral corneal opacity caused by corneal oedema. Congenital hyposomatotropism and possible secondary hypothyroidism were diagnosed on the basis of fasting serum levels of insulin-like growth factor-1 and thyroxine levels, respectively. These endocrinopathies are rare in the cat and have not been reported to cause ocular signs. The cat died during investigation of these diseases, and histopathological examination of the eyes showed significantly reduced corneal endothelial cell density and number of corneal epithelial cell layers when compared with age-matched healthy control corneas. These changes were implicated in the development of the corneal oedema.

Histopathological frequency of feline hepatobiliary disease in the UK.

OBJECTIVES: To determine the histopathological frequency of feline hepatobiliary diseases in the UK and to identify breed, age and gender predispositions to developing individual diseases. METHODS: Histopathology results from 1452 feline liver biopsies were assessed. A control population of microchipped cats was used for breed comparison. Data were retrospectively categorised into hepatobiliary diseases according to World Small Animal Veterinary Association standards. Odds ratios and 95% confidence intervals were calculated to determine breed predispositions to the 10 most frequent diseases. Gender and age distributions were also evaluated. RESULTS: The most frequent diseases based on histopathology were neutrophilic cholangitis (20·5%), reactive hepatitis (20·4%), reversible hepatocellular injury (8·4%), lymphocytic cholangitis (6·8%), biliary cysts (5·7%), acute hepatitis (5·6%), haematopoietic neoplasia (5·6%), hepatocellular neoplasia (4·9%), congenital portosystemic shunt (3·8%) and cholangiocellular neoplasia (3·1%). Some previously unreported breed and age predispositions were identified. CLINICAL SIGNIFICANCE: This is the first study to document the histopathological frequency of hepatobiliary diseases in a large cohort of cats in the UK, as well as novel breed and age predispositions. These data may help increase the index of suspicion of a particular disease in the absence of a biopsy-confirmed diagnosis.

Altered Nuclear Expression of the Deubiquitylase BAP1 Cannot be Used as a Prognostic Marker for Canine Melanoma.

BRCA1-associated protein-1 (BAP1) is a nuclear localized deubiquitylating enzyme that belongs to the ubiquitin c-terminal hydrolase subfamily. The encoded protein is highly homologous between man and dogs, suggesting a functional significance preserved by evolution. BAP1 has multiple properties, including tumour suppressor activity. Loss of BAP1 function is implicated in the oncogenesis of several types of cancers including uveal, mucosal and some cutaneous melanomas in humans, as well as in mesothelioma. In this study we investigate the significance of BAP1 in canine melanoma. Nuclear BAP1 protein was detected in five canine oral melanoma cell lines using an antibody commonly used for analysis of human tissues. BAP1 loss of function mutations often lead to loss of nuclear BAP1 (nBAP1) expression in humans; this is associated with a poorer prognosis in uveal and mucosal melanoma. Therefore, as a prelude to a study evaluating the prognostic significance of nBAP1 expression in dogs, immunohistochemistry (IHC) was used to assess cases of canine melanoma for nBAP1 expression. In 89 cases where tumour cells were identified by melan-A labelling, 100% of tumour cells were positive for nBAP1 expression, including eight uveal tract and 29 oral mucosal melanomas. This finding indicates that BAP1 IHC cannot be used as a prognostic marker in canine uveal and mucosal melanoma. Moreover, this observation suggests that either BAP1 has a different functional significance in canine melanoma or that loss of BAP1 function is achieved by a different route. This is a novel finding that warrants further investigation to determine the comparative biological relevance.

Immunohistochemical differentiation of reactive from malignant mesothelium as a diagnostic aid in canine pericardial disease.

OBJECTIVES: To develop a provisional immunohistochemistry panel for distinguishing reactive pericardium, atypical mesothelial proliferation and mesothelioma in dogs. MATERIALS AND METHODS: Archived pericardial biopsies were subject to haematoxylin and eosin staining, immunohistochemistry for cytokeratin, vimentin, insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1 and desmin. Samples were scored for intensity and number of cells stained. RESULTS: Ten biopsies of reactive mesothelium, 17 of atypical mesothelial proliferation, 26 of mesothelioma and five of normal pericardium were identified on the basis of haematoxylin and eosin staining. Cytokeratin and vimentin were expressed in all biopsies, confirming mesothelial origin. Normal pericardial samples had the lowest scores for insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1 and desmin. Mesothelioma and atypical proliferative samples were similar to each other, with higher scores for insulin-like growth factor II mRNA-binding protein 3 and glucose transporter 1 than the reactive samples. Desmin staining was variable. Insulin-like growth factor II mRNA-binding protein 3 was the best to distinguish between disease groups. CLINICAL SIGNIFICANCE: An immunohistochemistry panel of cytokeratin, vimentin, insulin-like growth factor II mRNA-binding protein 3 and glucose transporter 1 could provide superior information compared with haematoxylin and eosin staining alone in the diagnosis of cases of mesothelial proliferation in canine pericardium, but further validation is warranted.

Advances in the diagnosis and management of cutaneous mast cell tumours in dogs.

Mast cell tumours are one of the most common tumours of the canine skin and have a reputation for being difficult to manage because of their variable clinical presentation, behaviour and response to treatment. This review of recent literature on canine mast cell tumours suggests that the majority of such tumours may not be as bad as their reputation suggests. Most grade I and grade II tumours can be managed successfully by good surgery. Recent literature also calls into question the utility of clinical staging systems and the value of assessing surgical margins for prognosis and highlights the paucity of well-conducted, case-controlled clinical trials in assessing the efficacy of medical management of high-risk tumours. In terms of more basic research, recent studies have implicated the stem cell factor receptor KIT as having a role in the aetiology of canine mast cell tumours and there appears to be an association between c-kit mutation and higher grade of tumour. This may offer a possible target for new therapeutic approaches.

Survival of 54 cats with oral squamous cell carcinoma in United Kingdom general practice.

OBJECTIVES: To determine the survival of 54 cats with histologically confirmed feline oral squamous cell carcinoma (FOSCC) treated in UK general practice and to determine factors predictive for survival. METHODS: Cases were identified from consecutive samples submitted for histological diagnosis. Observational and survival data were collated retrospectively from submitting practices. Immunohistochemical analysis of cyclooxygenase (COX) expression variables was available using previously published data. Kaplan-Meier product limit estimation for overall survival and Cox proportional hazards regression for potential explanatory variables were performed. RESULTS: The overall median survival time was 44 days [95 per cent confidence interval (CI): 31-79] and 1 year survival was 9.5 per cent. Variables associated with survival were whether the cat was pedigree [hazard ratio (HR)=8.17, 95 per cent CI: 1.96-34.12], whether the cat received non-steroidal anti-inflammatory drug (NSAID) therapy after diagnosis (HR=0.46, 95 per cent CI: 0.21-0.98) and whether the COX-1 staining distribution was patchy rather than diffuse (HR=0.25, 95 per cent CI: 0.08-0.014). CLINICAL SIGNIFICANCE: This study suggests that although the prognosis for inoperable FOSCC remains poor, palliative treatments may offer a survival advantage that compares favourably with more aggressive treatment methods. Further work is needed to evaluate NSAID therapy in this disease, in particular to determine whether the potential survival advantage is because of an analgesic or anticancer effect or both. COX-1 distribution patterns may have a role as a prognostic indicator in this disease.

Prevalence and breed distribution of chronic pancreatitis at post-mortem examination in first-opinion dogs.

OBJECTIVES: To assess the prevalence of canine chronic pancreatitis in first-opinion practice and identify breed associations or other risk factors. METHODS: Three sections of pancreas were taken from 200 unselected canine post-mortem examinations from first-opinion practices. Sections were graded for inflammation, fibrosis and other lesions. Prevalence and relative risks of chronic pancreatitis and other pancreatic diseases were calculated. RESULTS: The prevalence of chronic pancreatitis was 34 per cent omitting the autolysed cases. Cavalier King Charles spaniels, collies and boxers had increased relative risks of chronic pancreatitis; cocker spaniels had an increased relative risks of acute and chronic pancreatitis combined. Fifty-seven per cent of cases of chronic pancreatitis were classified histologically as moderate or marked. Forty-one per cent of cases involved all three sections. Dogs with chronic pancreatitis were more commonly female and overweight, but neither factor increased the relative risk of chronic pancreatitis. There were breed differences in histological appearances and 24.5 per cent of cases were too autolysed to interpret with an increased relative risk of autolysis in a number of large breeds. CLINICAL SIGNIFICANCE: Chronic pancreatitis is a common, under-estimated disease in the first-opinion dog population with distinctive breed risks and histological appearances.