Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival

BACKGROUND: Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and vascular permeability. In human patients with meningiomas, increased VEGF expression is predictive of postsurgical recurrence. The objectives of this study were to evaluate VEGF expression in canine intracranial meningiomas and to determine whether an association between VEGF expression and patient survival existed. METHODOLOGY: Tumor tissue from 17 dogs with histologically confirmed intracranial meningiomas was obtained surgically. All dogs then were treated with radiotherapy. Immunohistochemistry was performed on 5-microm sections of paraffin-embedded tumor tissue with rabbit anti-human VEGF polyclonal antibody. The extent, intensity, and distribution of VEGF staining for each section were assessed with light microscopy by means of a semiquantitative scale. Survival was analyzed by the Kaplan-Meier procedure. Survival rates among groups were compared by log-rank tests with the significance set at P < or = .05. FINDINGS: VEGF expression was detected in all tumors, with >50% of cells staining positively in tissues from 15/17 dogs. Shorter survival times were associated with greater VEGF expression (P = .01). CONCLUSIONS: VEGF expression can be measured in canine intracranial meningiomas and may be associated with poor outcome. SIGNIFICANCE: The extent of VEGF expression in canine intracranial meningiomas may be used as a prognostic marker and suggests a potential future target for therapy.     

Detection of the Ki-67 Proliferation Associated Nuclear Epitope in Normal Canine Tissues Using the Monoclonal Antibody MIB-1

This report describes the immunohistochemical detection of the Ki-67 proliferation associated nuclear epitope by means of the MIB-1 monoclonal antibody (mAb) in paraffin tissue sections from nine samples of 16 tissues obtained from nine dogs. Three parameters were considered: the localization of the cells expressing the Ki-67 epitope, the cytological characteristics of the Ki-67 expression, and the proliferative activity of some of the tissues measured by means of the proliferative index (percentage of Ki-67 positive cells measured on 500 and 1000 cells). The MIB-1 mAb reacts with the nuclei of proliferating cells, as in humans. The proliferative index was far from representative, but we were able to give a range of values concerning the proliferative activity of normal tissues. This study serves as a basis for the expression of the Ki-67 antigen by normal canine tissues in order to visualize the proliferative compartments and, thus, allows its application as a proliferative marker in routine veterinarian histopathology.     

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.     

Cell proliferation in feline normal, hyperplastic and neoplastic mammary tissue--an immunohistochemical study

The expression of a proliferation cell marker in neoplastic and non-neoplastic mammary tissue in 31 cats was assessed by immunohistochemistry in formalin-fixed paraffin-embedded samples using a monoclonal antibody against nuclear antigen Ki-67 (MIB-1). The results revealed that cell proliferation was more intense in hyperplastic than in normal mammary tissue. Carcinomas exhibited a higher MIB-1 index than benign tumours. There was also a positive correlation between proliferative activity and the histological grade of carcinomas. Fibroadenomatous change, which is considered to be hyperplastic and associated with favourable biological behaviour, exhibited high proliferative activity involving both epithelial and mesenchymal components. MIB-1 detected in formalin-fixed material with pre-treatment with antigen retrieval solution appeared to be a reliable marker of proliferation in feline mammary tumours, but further studies are needed to investigate the value of this proliferation marker in predicting clinical outcome and/or as a prognostic factor in feline mammary lesions.     

Ki-67 and minichromosome maintenance-7 (MCM7) expression in canine pituitary corticotroph adenomas

Pituitary-dependent hyperadrenocorticism (PDH) caused by pituitary corticotroph adenoma is a common endocrine disorder in dogs. The ratio between pituitary height and the area of the brain (P/B) has been used to evaluate the pituitary size. A P/B ratio > 0.31 indicates an enlarged pituitary, whereas a P/B ratio ≤ 0.31 indicates a nonenlarged pituitary. The aim of this study was to investigate the expression of proliferation markers Ki-67 and minichromosome maintenance-7 (MCM7) in canine corticotroph adenomas in enlarged and in nonenlarged pituitaries and to evaluate their relation with the size of canine pituitary corticotroph adenomas. Ki-67 and MCM7 expression in ACTH-positive tumor cells was determined by dual-labeling immunohistochemistry in resected corticotroph adenomas from 15 dogs with PDH. The mean ± SD Ki-67 labeling index (LI) was 0.55% ± 0.59% in corticotroph adenomas with nonenlarged pituitaries and 1.6% ± 0.6% in adenomas with enlarged pituitaries. The MCM7 LI in corticotroph adenomas with nonenlarged pituitaries and in adenomas with enlarged pituitaries was 2.9% ± 2.2% and 10.9% ± 3.7%, respectively. The Ki-67 LI and MCM7 LI were significantly greater in the adenomas with enlarged pituitaries than in the adenomas with nonenlarged pituitaries (P < 0.01 and P < 0.01, respectively). The MCM7 LI was significantly greater than the Ki-67 LI in adenomas (P < 0.01). The Ki-67 LI was positively correlated with the MCM7 LI (r = 0.820, P < 0.01), and the P/B ratio was positively correlated with the Ki-67 LI (r = 0.560, P = 0.03) and the MCM7 LI (r = 0.854, P < 0.01). In conclusion, canine corticotroph adenomas in enlarged pituitaries show greater proliferation potential than do adenomas in nonenlarged pituitaries. MCM7 expression was significantly greater than Ki-67 expression in canine pituitary corticotroph adenomas. Thus, MCM7 may be superior to Ki-67 as a proliferation marker in pituitary tumors.     

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.     

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.     

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.     

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.     

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.     

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.     

Immunocytochemical study of Ki-67 as a prognostic marker in canine mammary neoplasia

Background: Canine mammary tumors are challenging for clinicians and pathologists because of complex histologic classification, low specificity of cytologic diagnosis, and unpredictable biological behavior. In histologic specimens, expression of tumor proliferation marker Ki‐67, a nuclear nonhistone protein, has been shown to have prognostic value for canine mammary tumors and to correlate with malignancy and low survival rates. Objective: The objective of this study was to measure the proliferation index of canine mammary tumors by immunochemical detection of Ki‐67 in cytologic specimens and to determine its relationship to clinical and pathologic variables and patient outcome. Methods: Spontaneous mammary tumors from 31 female dogs were surgically excised. Imprint specimens for cytologic evaluation were wet‐fixed in ethanol; histologic specimens were prepared routinely. Immunostaining was performed with the PH 177 monoclonal antibody against Ki‐67; proliferation index was graded from negative to +++. Dogs were followed for 18 months. Multivariate logistic regression analysis was used to determine correlations between immunocytochemical results, tumor and clinical variables, and patient outcome. Results: Ki‐67 proliferation indices in cytologic specimens were significantly lower for nonmalignant tumors than for malignant tumors. High index values of Ki‐67 were positively correlated with metastasis, death from neoplasia, low disease‐free survival rates, and low overall survival rate. With the exception of 4 specimens for which cellularity was insufficient, positive expression of Ki‐67 in cytologic specimens correlated with that of histologic specimens. Conclusions: The prognostic value of the Ki‐67 index in canine mammary tumors by using wet‐fixed cytology imprint specimens was similar to that observed previously for histologic specimens. Immunocytochemical detection of Ki‐67 could improve the accuracy and value of cytology by providing safe and rapid information about malignancy and patient outcome.     

Magnetic resonance imaging and histological classification of intracranial meningiomas in 112 dogs

BACKGROUND: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. HYPOTHESIS: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. ANIMALS: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. METHODS: Retrospective observational study. RESULTS: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas.     

Usefulness of Ki-67 proliferation marker in the cytologic identification of liver tumors in dogs

BACKGROUND: Performing a biopsy is currently the best method of diagnosing liver disease. To reduce possible risk factors resulting from a biopsy, liver cytology can provide an alternative technique. The diagnostic accuracy of cytology for identifying liver tumors is, however, limited. The results of cytology might be improved by using immunochemistry for Ki-67, a proliferation marker, on liver cytology specimens. OBJECTIVES: The purpose of this study was to investigate the value of Ki-67 immunochemistry on liver cytologic specimens from dogs for identifying neoplastic diseases of the liver, by comparing the results to histologic findings. METHODS: Liver biopsy and cytology samples were obtained from 30 dogs with hepatic disease. All samples were evaluated by an anatomic pathologist and a cytopathologist. Parallel Ki-67 immunochemistry of histologic and cytologic samples was performed. The gradation of Ki-67 expression in histologic and cytologic samples was assessed. RESULTS: Cytologic specimens of liver tumors (n = 9) showed <50% Ki-67-positive cells. Twenty of 21 cases of non-neoplastic liver disease had no or few single Ki-67-positive cells. Using Ki-67, the diagnostic accuracy of cytologic evaluation was increased from 78% to 100% for malignant neoplasia. CONCLUSIONS: Based on the results of this study, the cytologic evaluation of liver together with Ki-67 immunochemistry can improve the diagnostic accuracy of cytology for liver neoplasia.     

Immunohistochemical study of hormonal receptors and cell proliferation in normal canine mammary glands and spontaneous mammary tumours

The expression of hormone receptors and their relationship to cell proliferation in six samples of normal canine mammary tissue, and 11 benign and 10 malignant mammary neoplasms from female dogs were assessed by immunohistochemistry in formalin-fixed paraffin-embedded samples, by using monoclonal antibodies against progesterone and oestrogen receptors, and nuclear antigen Ki-67 (MIB-1). Malignant tumours negative for progesterone receptors proliferated at higher rates than progesterone receptor-positive tumours, suggesting that the progression towards malignancy in spontaneous mammary tumours is accompanied by a decrease in hormonal steroid dependency. Only one malignant tumour was positive for oestrogen receptors.     

MIB-1 labeling index in feline dysplastic and neoplastic mammary lesions and its relationship with postsurgical prognosis

Samples from feline normal, dysplastic, and neoplastic mammary tissues were used to investigate the usefulness of MIB-1 labeling index (MIB-1 I) as a prognostic indicator. Forty-eight queens bearing invasive carcinomas were included in a 2-year follow-up study. Mammary lesions were classified according to the World Health Organization system, and invasive carcinomas were further graded on the basis of the degree of tubule formation, the degree of nuclear and cellular pleomorphism, and mitotic count. Additional sections were immunostained using MIB-1 antibody, and MIB-1 I was expressed as a percentage of positive nuclei. In normal mammary gland tissues, the mean MIB-1 I was <1%. A low proliferation rate was found in all mammary adenosis and in situ carcinomas, and the highest rates were observed in feline mammary hypertrophy and invasive carcinomas. Twenty-one (43.7%) of the queens bearing invasive carcinomas were still alive at the end of the trial, and 27 (56.2%) had died. The MIB-1 I was not significantly correlated with clinical outcome, age, histologic type, or grading of the tumors, but a borderline correlation was observed with invasion of lymphatic vessels. Univariate analysis showed that high MIB-1 I was also not associated with decreased overall survival, whereas the grading system of the tumors had high predictive value (P = 0.0040) for postsurgery survival. The lack of correlation between MIB-1 I and postsurgery survival suggests that this marker alone is not sufficient to determine a correct prognosis in feline mammary carcinomas, even if it is a useful proliferation marker.     

Blood Lactate Concentrations in Anesthetized Dogs with Intracranial Disease

Background: The importance of blood lactate concentrations in dogs with intracranial disease has not been established, despite frequently observed hyperlactatemia in dogs undergoing general anesthesia for advanced imaging, surgery, or both.
Hypothesis: Blood lactate concentrations are elevated in anesthetized dogs with intracranial disease, compared with dogs with intervertebral disc disease (IVDD).
Animals: Eighty-five hospitalized dogs undergoing advanced imaging, surgery, or both for primary neurologic disease; 30 with intracranial disease; 55 with IVDD.
Methods: Retrospective study. Age, breed, neurologic diagnosis, time from anesthesia induction to measurement of blood lactate, blood lactate concentration under anesthesia, and concurrently measured heart rate, mean arterial pressure, PCV, arterial hemoglobin oxygen saturation, and arterial partial pressure of oxygen were included in a multivariable linear regression analysis.
Results: Dogs with meningioma (adjusted mean lactate 2.99 mmol/L, 95% CL 2.21–4.05, P < 0.0001) and hydrocephalus (adjusted mean lactate 1.5 mmol/L, 95% CL 0.99–2.27, P = 0.003) had higher blood lactate concentrations compared with dogs with IVDD (adjusted mean lactate 0.79 mmol/L, 95% CL 0.6–1.04). Only dogs with meningioma had clinically important hyperlactatemia (>2.5 mmol/L).
Conclusions: Prospective studies are warranted to determine the degree and clinical importance of high blood lactate concentrations in dogs with intracranial disease.     

Proliferation activity in oral and cutaneous canine melanocytic tumours: correlation with histological parameters,location, and clinical behaviour

A total of 62 canine melanocytic tumours (10 melanocytomas and 52 primary malignant melanomas) were investigated to compare the accuracy of prognosis provided by MIB-1 proliferation index (MIB-1-PI) with classical histological criteria and location. MIB-1-PI was assessed by means of quantitative image analysis of sections immunostained with MIB-1 monoclonal antibody. Tumour location, histological cell type, stromal or lymphatic vessel invasion, maximum tumour thickness, and presence of inflammation or necrosis were recorded for each case. Thirty-eight dogs were submitted to a 1-year follow-up and the clinical outcome of the disease determined. MIB-1-PI in melanocytomas differed significantly from that detected in primary malignant melanomas (P=0.0001). A significant difference in MIB-1-PI was revealed between oral and cutaneous malignant melanomas (P=0.015), and between presence and absence of lymphatic vessel invasion (P=0.05). MIB-1-PI was not correlated with the other parameters. In univariate analysis, only tumour location (oral vs cutaneous), presence of lymphatic vessel invasion, and MIB-1-PI were associated with decreased overall survival (P=0.0001,P=0.0144, and P=0.0489, respectively). In conclusion, the results of our study confirm that the assessment of the MIB-1-PI may be of additional prognostic value for dogs with primary malignant melanomas.     

Apoptotic and proliferation indexes in canine lymphoma.

Proliferative and apoptotic fractions of tumors were evaluated in 41 dogs with lymphoma for prediction of response to chemotherapy. All dogs had advanced clinical stage tumors, were untreated prior to study, and received identical induction-remission chemotherapy. Tumor cell proliferation was determined in all pretreatment biopsy specimens and in 18 specimens collected at the time of clinical relapse from remission. Quantitative measures included mitotic index and immunoreactivities for proliferating cell nuclear antigen (PCNA) and Ki-67. Apoptotic index was evaluated from 40 dogs pretreatment and from 16 dogs at the time of first relapse. Pretreatment tumor values for Ki-67, PCNA, and apoptosis were compared with posttreatment values. The median first relapse-free interval (RFI) and overall survival (OS) time were 174 days and 445 days, respectively. Of the proliferation markers, only the results of the Ki-67 analysis were predictive for duration of the first RFI but not OS. Pretreatment apoptotic index was also predictive of the duration of first RFI but not OS. No significant predictive value for comparison of the pretreatment and postrelapse values was demonstrated. Ki-67 labeling index and apoptotic indexes were combined to form both a proliferation/apoptotic ratio (PAR) and a sum, or turnover index. Only the PAR was predictive for duration of first RFI on multivariate analysis. Other variables that were evaluated for their influence on treatment outcome included patient age, weight, gender, clinical stage, clinical substage, and tumor immunophenotype. Of these variables, only immunophenotype was found to be of value for predicting duration of first RFI and OS.     

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.