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.     

Expression of vascular endothelial growth factor in canine oral malignant melanoma

Serum, plasma and tissue expression of vascular endothelial growth factor (VEGF) was measured in 20 dogs previously diagnosed histologically with oral melanoma. The concentrations of VEGF in serum and plasma were significantly higher in dogs with melanoma than in a control population (P ≤ 0.002). Concentrations of VEGF in the serum and plasma of dogs with melanoma were highly correlated (r = 0.867). Ninety‐five per cent of melanoma tissues expressed VEGF. Two staining patterns were detected: diffuse and granular cytoplasmic staining. High blood concentrations of VEGF were correlated to a shorter survival time in dogs receiving definitive therapy (P = 0.002). Survival times were significantly longer in dogs receiving definitive therapy versus palliative therapy (median 496 versus 97 days, P = 0.007). Blood concentrations of VEGF were associated with stage (P < 0.05). Dogs with oral melanoma have increased serum, plasma and tissue concentrations of VEGF. Increased expression of VEGF may be a reasonable target for future therapy of canine oral melanoma.     

Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms

OBJECTIVE: To quantitatively evaluate expression of vascular endothelial growth factor (VEGF) in intracranial tumors in dogs and determine whether relationships exist between circulating and intratumoral VEGF concentrations and tumor type and grade. ANIMALS: 27 dogs with primary intracranial neoplasms and 4 unaffected control dogs. PROCEDURES: Plasma and brain tumor samples were obtained from each dog, and plasma and intratumoral concentrations of VEGF were measured by use of an ELISA. RESULTS: Dogs with meningiomas (n = 11) were significantly older than dogs with oligodendrogliomas (7) or astrocytomas (9). Measurable VEGF was detected in all tumors, and a significant negative correlation between age and intratumoral VEGF concentration was detected. Age-adjusted comparisons identified significant differences in intratumoral VEGF concentrations among all tumor types; the highest VEGF concentrations were associated with astrocytomas. Within each tumor type, increasing tumor grade was significantly associated with increasing VEGF expression. Plasma VEGF concentrations were detectable in 9 of 27 dogs; the proportion of dogs with astrocytomas and a detectable circulating VEGF concentration (7/9 dogs) was significantly higher than the proportion of dogs with meningiomas (1/11 dogs) or oligodendrogliomas (1/7 dogs) with a detectable circulating VEGF concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Overexpression of VEGF appears common in canine astrocytomas, oligodendrogliomas, and meningiomas. In the neoplasms examined, intratumoral VEGF concentrations correlated well with tumor malignancy. The VEGF expression patterns paralleled those of analogous human tumors, providing evidence that dogs are a suitable species in which to study angiogenesis and intracranial neoplasia for human application.     

Evaluation of intracranial meningioma resection with a surgical aspirator in dogs: 17 cases (1996-2004)

OBJECTIVE: To determine results of intracranial meningioma resection by use of a surgical aspirator and assess prognostic factors associated with intracranial meningiomas in dogs. DESIGN: Retrospective case series. ANIMALS: 17 dogs. PROCEDURES: Medical records of dogs that underwent resection of an intracranial meningioma by use of a surgical aspirator were reviewed. Information pertaining to signalment, imaging findings, clinical signs, duration of clinical signs, preoperative treatment, location of the tumor, results of histologic assessment, outcome, and necropsy results was obtained from the medical record. Clients and referring veterinarians were contacted via telephone for information on recurrence of clinical signs and postoperative survival time. RESULTS: 16 dogs were > 7 years of age, and all 17 dogs had seizures before surgery. The most commonly affected breed was the Golden Retriever, represented by 6 of the 17 dogs. Median survival time was 1,254 days. Of the data collected, only histologic subtype of the tumor was prognostic. Analysis of survival times according to histologic tumor subtypes indicated that the order from most brief to longest was as follows: anaplastic, 0 days; fibroblastic, 10 days; psammomatous, > 313 days; meningothelial, > 523 days; and transitional, 1,254 days. CONCLUSIONS AND CLINICAL RELEVANCE: Use of a surgical aspirator to resect intracranial meningiomas in dogs was associated with longer survival times than those achieved with traditional surgery alone or traditional surgery combined with radiation therapy. Dogs with meningothelial, psammomatous, or transitional intracranial meningioma subtypes appeared to have a better prognosis than dogs with other subtypes of meningioma.     

Evaluation of progesterone and estrogen receptor expression in 15 meningiomas of dogs and cats

OBJECTIVE: To evaluate progesterone and estrogen receptor expression in meningiomas of the CNS in dogs and cats. ANIMAL: 8 dogs (1 of which was treated with gestrinone) and 5 cats with intracranial meningiomas and 2 dogs with spinal cord meningiomas; tissue samples were also obtained from 1 clinically normal dog and 1 clinically normal cat. PROCEDURE: Meningioma tissue was obtained during surgery or at necropsy; samples were processed for histologic classification and immunohistochemical evaluation of the proportion of tumor cells with progesterone and estrogen receptors. Correlation among receptor expression, tumor grade, and histologic subtypes was determined. RESULT: Several histologic subtypes of intracranial meningiomas were detected among tissue samples. In the cats, all intracranial meningiomas were benign. Progesterone receptor immunoreactivity was detected in 14 of 15 meningiomas. Progesterone receptor expression was identified in > 80% of cells in 8 intracranial meningiomas (4 dogs and 4 cats) and 2 spinal cord meningiomas. In samples of malignant transitional and granular cell meningiomas in dogs, progesterone receptors were detected in 32 and 4.8% of cells respectively. In 1 cat, 38% of tumor cells had progesterone receptors. In a dog treated with gestrinone, no progesterone receptors were detected in the intracranial meningioma. Estrogen receptors were only detected in the tumor of 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate a high proportion of progesterone receptors in cells of meningiomas of the CNS in dogs and cats. Antiprogesterone treatment may have a role in the treatment of unresectable or recurrent meningiomas in dogs and cats.     

Immunoexpression of epithelial membrane antigen in canine meningioma: Novel results for perspective considerations

Epithelial membrane antigen (EMA) is one of the most widely used diagnostic immunohistochemical markers for human meningioma. To date, no published study on EMA expression in formalin‐fixed paraffin‐embedded (FFPE) tissue samples of canine meningioma is available. Here, we describe the results of an immunohistochemical study on 25 FFPE canine meningiomas using a monoclonal anti‐human EMA antibody. All meningiomas showed positive staining for EMA with cytoplasmic pattern, in nine cases associated with membranous staining. Area and intensity of staining were highly variable among cases. No clear relationships between tumour subtype/grade and area/intensity of staining were found. However, epithelial‐like patterns showed a higher affinity for EMA compared to the mesenchymal one. The present study provides the basis to explore the potential diagnostic application of this marker in canine meningioma. To investigate EMA expression in other central nervous system tumours of dogs are necessary to assess the specificity of this marker.     

Single fraction stereotactic radiation therapy (stereotactic radiosurgery) is a feasible method for treating intracranial meningiomas in dogs

The aim of this retrospective, pilot study was to evaluate stereotactic radiosurgery as a method for treating intracranial meningiomas in dogs. Included dogs had an imaging diagnosis of presumed intracranial meningioma, were treated using a standardized stereotactic radiosurgery protocol, and had a follow‐up time of >6 months after stereotactic radiosurgery. A single fraction of 16 Gy stereotactic radiosurgery was delivered to the tumor, with an internal simultaneously integrated boost to a total dose of 20–24 Gy to the central portion of the tumor. Thirty‐two dogs were sampled. One dog was euthanized in the periprocedural period, and 10 of the remaining 31 dogs (31%) experienced an acute adverse event (defined as declining neurologic function due to tumor progression or treatment‐associated complication within the first 6 months after stereotactic radiosurgery), three of which were fatal. Too few subjects (n = 6) had cross‐sectional imaging after stereotactic radiosurgery to determine an objective response rate; however, 17/30 (57%) dogs assessed for response had a perceived clinical benefit from treatment. The overall median survival time was 519 days (95% confidence interval: 330–708 days); 64% and 24% of dogs were alive at 1 and 2 years after stereotactic radiosurgery, respectively. Dogs with infratentorial tumor location and high gradient indices had shorter survival. There were no factors identified which were predictive of acute adverse event. Survival times reported herein are similar to what has previously been reported for other stereotactic and traditional fractionated radiotherapy protocols. Findings therefore supported the use of stereotactic radiosurgery as an alternative method for treating dogs with presumed intracranial meningiomas.     

Endostatin and vascular endothelial growth factor concentrations in healthy dogs, dogs with selected neoplasia, and dogs with nonneoplastic diseases

To evaluate the relationship between endostatin and vascular endothelial growth factor (VEGF) in cancers of dogs, circulating concentrations of these 2 tumor-associated markers were measured prospectively in healthy dogs (n = 44), dogs with tumors (n = 54), and dogs with nonneoplastic diseases (n = 42 for endostatin; n = 16 for VEGF). A canine-directed enzyme-linked immunosorbent assay kit was used for determination of endostatin, and a human-directed kit was validated for detection of canine VEGF. Concentrations of endostatin for all dogs were 28-408 ng/mL. Increasing serum endostatin concentration was associated with increasing age (P = .0396). Concentrations of endostatin were not different among groups of dogs (P = .1989) when adjusted for age. Mean endostatin concentrations for all dogs were higher in dogs (P = .0124) with detectable VEGF concentrations. Endostatin concentrations, when corrected for age, were related to decreasing PCV (P = .032) but not white blood cell count (P = .225) or platelet count (P = .1990). Measurable VEGF (> or = 2.5 pg/mL) was detected in 3 (7.0%) of 43 healthy dogs. Dogs with tumors had detectable VEGF in 24 (44%) of 54 dogs, with concentrations ranging from 2.5-274 pg/mL; only 1 dog with a nonneoplastic disease process had detectable VEGF. VEGF concentrations for all dogs after correcting for age, endostatin, and disease categories were associated with increased white blood cell count (P = .0032) and platelet counts (P = .0064) and decreased PCV (P = .0017). Linkage between increased endostatin and VEGF concentrations suggests that similar factors may influence concentrations of these markers. Further evaluation of endostatin and VEGF associations in dogs with tumors may provide information on the extent and progression of the disease.     

Surgery alone or in combination with radiation therapy for treatment of intracranial meningiomas in dogs: 31 cases (1989-2002)

OBJECTIVE: To compare, for dogs with intracranial meningiomas, survival times for dogs treated with surgical resection followed by radiation therapy with survival times for dogs treated with surgery alone. DESIGN: Retrospective study. ANIMALS: 31 dogs with intracranial meningiomas. PROCEDURE: Medical records of dogs with histologic confirmation of an intracranial meningioma were reviewed. For each dog, signalment, clinical signs, tumor location, treatment protocol, and survival time were obtained from the medical record and through follow-up telephone interviews. RESULTS: Dogs that underwent tumor resection alone and survived > 1 week after surgery had a median survival time of 7 months (range, 0.5 to 22 months). Dogs that underwent tumor resection followed by radiation therapy had a median survival time of 16.5 months (range, 3 to 58 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that in dogs with intracranial meningiomas, use of radiation therapy as a supplement to tumor resection can significantly extend life expectancy.     

Characteristics of cisternal cerebrospinal fluid associated with intracranial meningiomas in dogs: 56 cases (1985-2004)

OBJECTIVE: To determine CSF characteristics associated with intracranial meningiomas in dogs. DESIGN: Retrospective case series. ANIMALS: 56 dogs with intracranial meningiomas. PROCEDURES: Medical records of dogs with a histopathologic diagnosis of intracranial meningioma, in which CSF analysis had been performed, were reviewed. Information concerning total nucleated cell counts (TNCCs) and differential nucleated cell counts, RBC counts, and total protein concentration in CSF; seizure history and glucocorticoid administration; and location of meningiomas was recorded. RESULTS: TNCCs < 5 cells/microL were detected in 41 of 56 (73%) dogs; 5 of 56 (9%) dogs had TNCCs > 50 cells/microL. Analysis of CSF revealed predominantly neutrophilic pleocytosis in < 20% of dogs. There was a significant association between meningioma location (caudal portion of the cranial fossa or middle and rostral portion of the cranial fossae) and increased TNCCs (> or = 5 cells/microL). CONCLUSIONS AND CLINICAL RELEVANCE: Results were significantly different from those routinely reported in the veterinary literature. Neutrophilic pleocytosis, especially with TNCCs > 50 cells/microL, was not typical in CSF samples from dogs with intracranial meningiomas. Neutrophilic pleocytosis may not be detected in CSF samples from dogs with meningiomas located within the middle or rostral portion of the cranial fossae.     

Endoscopic-Assisted Intracranial Tumor Removal in Dogs and Cats: Long-Term Outcome of 39 Cases

Background: The benefits of endoscopic assistance to remove intracranial tumors in small animals are not described.
Objective: To evaluate the effectiveness of endoscopic-assisted intracranial tumor removal in dogs and cats.
Animals: Thirty-three dogs and 6 cats with intracranial tumors.
Methods: Retrospective study. CBC, serum chemistry profile, coagulation testing, blood typing, and systemic tumor staging, which included 3-view thoracic radiographs and abdominal ultrasound examination, were performed to detect other significant underlying disease in preparation of the animal for surgery. Magnetic resonance imaging was used in 37/39 cases to image the brain tumor. Surgical approach was dictated by the location of the tumor. Histopathologic examination of the tumor tissue was performed in all cases. Animals were followed throughout their postoperative course for complications and survival times. Statistical analysis (Kaplan-Meier curves) was performed to obtain median survival times in dogs with meningiomas.
Results: Use of an endoscope resulted in visualization of residual tumor and potentially more complete removal of the brain tumors. There were no clinically important complications associated with the use of the endoscope. Median survival time was 2,104 days for dogs with forebrain meningiomas surgically removed with endoscopic assistance and 702 days for dogs with caudal brain meningiomas.
Conclusions and Clinical Importance: These results demonstrate that the use of an endoscope to assist in brain tumor removal is apparently safe and might result in improved survival times.     

Prognostic factors in canine exocrine pancreatic insufficiency: prolonged survival is likely if clinical remission is achieved

BACKGROUND: Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients. HYPOTHESIS: Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and therapeutic regimen employed. ANIMALS: Client-owned dogs diagnosed with EPI between 1990 and 2002 were included in this study. METHODS: The study comprised a retrospective, questionnaire-based review. RESULTS: One hundred seventy-eight completed questionnaires were returned. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P = .037) or had high serum folate concentration (P = .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat-restricted diet could be demonstrated, but marked hypocobalaminemia (< 100 ng/L) was associated with shorter survival (P = .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis ( < or = 4 years or > 4 years), and clinical signs at diagnosis also made no difference. CONCLUSIONS AND CLINICAL IMPORTANCE: Long-term prognosis in canine EPI is favorable for dogs that survive the initial treatment period. Although there are few predictors of good RIT or long-term survival, severe cobalamin deficiency is associated with shorter survival. Therefore, parenteral cobalamin supplementation should be considered when hypocobalaminemia is documented.     

The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: a preliminary study of autocrine and paracrine loops

Vascular Endothelial Growth Factor (VEGF) and its receptor KDR are involved in the regulation of angiogenesis and are up-regulated in a number of tumours in humans and in particular, breast cancer. We therefore evaluated the prognostic potential of the angiogenetic process in feline and canine mammary carcinomas by the immunohistochemical assessment of VEGF expression and micro vessel density (MVD) quantification and examined the interplay between VEGF and KDR. These variables were related to some relevant clinicopathological parameters and to overall survival (OS). VEGF and KDR expression were evaluated in epithelial, stromal and endothelial compartments in order to identify autocrine and/or paracrine loops. In dogs an increased VEGF expression did not show any statistical correlation with the clinicopathological parameters examined and was not correlated to a poorer prognosis. MVD was found to be significantly correlated to the histologic type (P=0.04), tumour grading (P=0.02), and to the OS (P=0.01). In cats VEGF expression was significantly correlated to tumor grading (P=0.01) and OS (P=0.03), while no significant associations were found between MVD and the other parameters. VEGF and KDR were found to be detected on the epithelial, and/or endothelial and/or stromal cells of the carcinomas in both species, suggesting indications for some possible autocrine and paracrine loops. Our results encourage further studies on the possible prognostic role of VEGF and MVD in canine and feline mammary tumours and on the role of growth factors and their receptors in promoting tumour proliferation and an "angiogenetic shift". The VEGF/KDR system may play a role in malignant transformation and tumor progression.     

Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor associated with tumor cell proliferation in canine cutaneous squamous cell carcinomas and trichoepitheliomas

The expression of 5 markers associated with angiogenesis was studied in canine squamous cell carcinomas (SCCs) (n = 19) and canine trichoepitheliomas (TCPs) (n = 24). SCCs were assigned histologic grades, and tissue sections from both tumor types were immunohistochemially stained for the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), as well as intratumoral microvessel density (iMVD), tumor proliferation index (PI), and tumor apoptotic index (AI), using antibodies against VEGF, VEGFR-2, von Willebrand's factor, Ki-67 antigen, and the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate end-labeling method (TUNEL), respectively. VEGF and VEGFR-2 were detected in 17/19 (89.4%) and 19/19 (100%) SCCs and in 17/24 (70.8%) and 20/24 (83.3%) TCPs, respectively. In SCCs, there was substantial correlation between histologic grade and PI (r = 0.51); and moderate correlation between VEGF and histologic grade (r = 0.43), VEGFR-2 and histologic grade (r = 0.47), VEGF and PI (r = 0.47), and VEGFR-2 and PI (r = 0.47) (Spearman rank correlation coefficient). In TCPs, there was substantial correlation between VEGF and PI (r = 0.51) and a moderate correlation between VEGFR-2 and iMVD (r = 0.36). The median iMVD of SCCs (15.5) was significantly higher than the median iMVD of TCPs (9.05) (P value < .05). It was concluded that VEGF and VEGFR-2 may promote tumor cell proliferation in TCPs and SCCs. An autocrine pathway for VEGF probably operates in canine SCCs and TCPs, as VEGF and VEGFR-2 expression was found in most tumors and was associated with evidence for tumor cell proliferation.     

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.     

Association of body weight and body condition with survival in dogs with heart failure

BACKGROUND: Obesity is a risk factor for cardiovascular disease in people, but overweight and obese human heart failure patients have improved survival compared with normal--or underweight controls--the obesity paradox. The purpose of this study was to determine if there is an association of body weight and body condition with survival in dogs with heart failure. HYPOTHESIS: That body condition and changes in body weight are predictors of survival in dogs with heart failure. ANIMALS: One hundred and eight dogs with heart failure (International Small Animal Cardiac Health Council stages 2, 3a, or 3b) secondary to dilated cardiomyopathy or chronic valvular disease. METHODS: Medical records were reviewed, and data regarding initial body weight and body condition score (BCS), subsequent changes in body weight, and treatment were collected. Survival times were determined for dogs that were discharged from the hospital and lived >24 hours. RESULTS: Survival was significantly different between dogs that gained, lost, or maintained body weight over the course of their disease (P= .04), with dogs that gained weight surviving the longest. BCS and medications were not significantly associated with survival time; however, n-3 fatty acid intake was associated with longer survival time (P= .009). CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that changes in body weight might be an important consideration in the survival of dogs with heart failure.     

The use of KIT and tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors

Cutaneous mast cell tumors (MCTs) are one of the most common tumors in dogs. Currently, prognostic and therapeutic determinations for MCTs are primarily based on the histologic grade of the tumor, but a vast majority of MCTs are of an intermediate grade, and the prognostic relevance is highly questioned. A more detailed prognostic evaluation, especially of grade 2 canine MCTs, is greatly needed. To evaluate the prognostic significance of KIT and tryptase expression patterns in canine cutaneous MCTs, we studied 100 cutaneous MCTs from 100 dogs that had been treated with surgery only. The total survival and disease-free survival time and the time to local or distant recurrence of MCTs were recorded for all dogs. Using immunohistochemistry, 98 of these MCTs were stained with anti-KIT and antitryptase antibodies. Three KIT- and three tryptase-staining patterns were identified. The KIT-staining patterns were identified as 1) membrane-associated staining, 2) focal to stippled cytoplasmic staining with decreased membrane-associated staining, and 3) diffuse cytoplasmic staining. The tryptase-staining patterns were identified as 1) diffuse cytoplasmic staining, 2) stippled cytoplasmic staining, and 3) little to no cytoplasmic staining. Based on univariate and multivariate survival analysis, increased cytoplasmic KIT staining was significantly associated with an increased rate of local recurrence and a decreased survival rate. The tryptase-staining patterns were not significantly associated with any survival parameter. On the basis of these results, we propose a new prognostic classification of canine cutaneous MCTs, according to their KIT-staining pattern, that can be used for the routine prognostic evaluation of canine cutaneous MCTs.     

Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas

Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotheraputic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis.     

Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours*

Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) signalling pathways play a role in carcinogenesis. Inhibition of EGF receptor (EGFR) and of VEGF is effective in increasing the radiation responsiveness of neoplastic cells both in vitro and in human trials. In this study, immunohistochemical evaluation was employed to determine and characterize the potential protein expression levels and patterns of EGFR and VEGF in a variety of canine malignant epithelial nasal tumours. Of 24 malignant canine nasal tumours, 13 (54.2%) were positive for EGFR staining and 22 (91.7%) were positive for VEGF staining. The intensity and percentage of immunohistochemically positive neoplastic cells for EGFR varied. These findings indicate that EGFR and VEGF proteins were present in some malignant epithelial nasal tumours in the dogs, and therefore, it may be beneficial to treat canine patients with tumours that overexpress EGFR and VEGF with specific inhibitors in conjunction with radiation.