Infantile hemangioma in a subadult Chinese pangolin: a case report.

BACKGROUND: Hemangiomas are a relatively common type of tumor in humans and animals. Various subtypes of hemangiomas have been described in the literature. The classification methods for hemangiomas differ between human and veterinary medicine, and the basis for tumor classification can be found in the literature. CASE PRESENTATION: This study describes a tumor in the subcutaneous tissue of the right dorsum of an artificially rescued juvenile Chinese pangolin. Computed tomography (CT) examination yielded the preliminary diagnosis of a vascular malformation, and surgery was performed to resect the tumor. Histopathological examination showed that the tumor mainly was consisted of adipose tissue, capillaries, and spindle cells in the fibrous stroma. Immunohistochemistry showed the positive expression of CD31, CD34, α-SMA, GLUT1 and WT-1 in the tumor tissue, and the tumor was eventually diagnosed as an infantile haemangioma. CONCLUSION: The final diagnosis of infantile hemangioma was depended on the histopathological immunohistochemical and CT examination of the neoplastic tissue. This is the first report of infantile hemangioma in a critically endangered species Chinese pangolin.

Intestinal hemangiomas in 8 horses.

This retrospective study describes 8 cases of intestinal hemangioma diagnosed in horses during postmortem examination or surgical biopsy at the University of Tennessee College of Veterinary Medicine. In all cases, the intestine was the sole organ affected, and lesions were focal (3/8) or multifocal (5/8). Nodules were most commonly within the small intestine (7/8), particularly the jejunum (5/7). One case was in the left dorsal colon, which is the first report of hemangioma in the large colon of a horse. Lesions were discrete, raised, smooth, black to red, and ranged from 2 to 15 mm in diameter. Microscopically, all lesions were cavernous type and mural, most frequently within the muscularis (6/8). A majority of cases occurred in middle aged to older horses (average age of 19.3 years), and no breed or sex predilections were identified. The hemangiomas were considered incidental findings.

Capillary gingival hemangioma in a cat.

A 12-year-old spayed female American short-haired cat presented with a palatal gingival mass located between the right maxillary third incisor and the canine teeth. The mass was dark red and had a narrow attachment to the gingival margin of the canine tooth. The mass was completely removed by marginal excision and the histopathological diagnosis was a capillary hemangioma. The mass did not relapse until 1 year later; however, the tooth was extracted because of cervical resorption of the right maxillary canine immediately adjacent to the mass resection site. This report presents a rare case of the gingival hemangioma in a cat and the possibility of a causal relationship between the occurrence of external cervical tooth resorption and hemangioma resection.

Granulation tissue-type hemangioma in a 6-week-old puppy - a case report.

BACKGROUND: Hemangioma is a well-known neoplasia in veterinary and human medicine. Several subtypes have been described and are distinguished based on their histologic appearance. The classification schemes of hemangiomas in human and veterinary medicine are different, and various purpose-based schemes can be found in the literature. CASE PRESENTATION: A six-week-old puppy was presented that suffered from a neoplasia that extended to the musculature of the hind limb. After surgical excision, the mass was submitted for pathohistological examination. The mass was composed of endothelial cells forming vascular slits admixed with a fibrous stroma and spindle cells. Immunohistological examination was positive for factor VIII-related antigen and smooth muscle actin, supporting the diagnosis of hemangioma. CONCLUSION: The final diagnosis of granulation tissue-type hemangioma was given due to the histological appearance of the neoplasia. Granulation tissue-type hemangioma is a rare subtype of hemangioma. In this case an uncommonly young dog was affected.

Intracranial Virotherapy for a Canine Hemangioma.

Intracranial hemangiomas are rare neoplastic lesions in dogs that usually appear with life-threatening symptoms. The treatment of choice is tumor resection; however, complete resection is rarely achieved. The patient's prognosis therefore usually worsens due to tumor progression, and adjuvant treatments are required to control the disease. Oncolytic viruses are an innovative approach that lyses the tumor cells and induces immune responses. Here, we report the intratumoral inoculation of ICOCAV15 (an oncolytic adenovirus) in a canine intracranial hemangioma, as adjuvant treatment for incomplete tumor resection. The canine patient showed no side effects, and the tumor volume decreased over the 12 months after the treatment, as measured by magnetic resonance imaging using volumetric criteria. When progressive disease was detected at month 18, a new dose of ICOCAV15 was administered. The patient died 31.9 months after the first inoculation of the oncolytic adenovirus. Furthermore, tumor-infiltrated immune cells increased in number after the viral administrations, suggesting tumor microenvironment activation. The increased number of infiltrated immune cells, the long survival time and the absence of side effects suggest that ICOCAV15 could be a safe and effective treatment and should be further explored as a novel therapy for canine hemangiomas.

The immunohistochemical detection of peroxiredoxin 1 and 2 in canine spontaneous vascular endothelial tumors.

Peroxiredoxin (PRDX) is an antioxidant enzyme family with six isoforms (PRDX1-6). The main function of PRDXs is to decrease cellular oxidative stress by reducing reactive oxygen species, such as hydrogen peroxide, to H2O. Recently, it has been reported that PRDXs are overexpressed in various malignant tumors in humans, and are involved in the development, proliferation, and metastasis of tumors. However, studies on the expression of PRDXs in tumors of animals are limited. Therefore, in the present study, we immunohistochemically investigated the expression of PRDX1 and 2 in spontaneous canine hemangiosarcoma (HSA) and hemangioma (HA), as well as in selected normal tissue and granulation tissue, including newly formed blood vessels. Although there were some exceptions, immunolocalization of PRDX1 and 2 in normal canine tissues was similar to those in humans, rats, or mice. In granulation tissue, angiogenic endothelial cells were strongly positive for PRDX1 and 2, whereas quiescent endothelial cells in mature vessels were negative. Both PRDX1 and 2 were significantly highly expressed in HSA compared to HA. There were no significant differences in the expression of PRDX1 and 2 among the subtypes and primary sites of HSA. These results suggest that PRDX1 and 2 may be involved in the angiogenic phenotypes of endothelial cells in granulation tissue as well as in the behavior in the malignant endothelial tumors.

Gene expression profiles of beta-adrenergic receptors in canine vascular tumors: a preliminary study.

Beta adrenergic receptors (ß-AR) play a key role in regulating several hallmark pathways of both benign and malignant human and canine tumors. There is scarce information on the expression of ß-AR in canine vascular tumors. Therefore, the purpose of the present research work was to study the mRNA expression levels of the three subtypes of the ß-AR genes (ADRB1, ADRB2, ADRB3) in hemangiosarcoma (HSA) and hemangioma (HA), as well as in vascular hamartomas (VH) from dogs.Fifty samples (n = 50) were obtained from 38 dogs. Twenty-three animals had HSA, eight animals HA and seven animals VH. HSA were auricular (n = 8), splenic (n = 5), cutaneous (n = 6), auricular and splenic (n = 2), cutaneous-muscular (n = 1) and disseminated (n = 1). There were seven cases of HSA that were divided into primary tumor and secondary (metastatic) tumor. Skin and muscle samples with a normal histological study were used as control group. ADRB gene expression was determinate in all samples by real-time quantitative PCR. Results showed that ADRB1, ADRB2 and ADRB3 were overexpressed in HSA when compared to the control group. ADRB2 was overexpressed in HA when compared to the control group. HSA express higher values of ADBR1 (p = 0.0178) compared to VH. There was a high inter-individual variability in the expression of the three subtypes of ADBR. No statistically significant difference in the expression of ADBR genes were observed between HSA primary when compared to metastatic or in different anatomical locations. In conclusion, canine HSA overexpress the three ß-AR subtypes and canine HA ß2-AR. High variability was observed in ß-AR mRNA levels amongst HSA cases.

Surgical treatment of conjunctival hemangioma and hemangiosarcoma: A retrospective study of 52 dogs.

OBJECTIVE: To review cases of canine conjunctival hemangioma (HA) and hemangiosarcoma (HSA) treated surgically at a referral center to establish success of surgical management, recurrence rates, and long-term outcomes for patients. ANIMALS STUDIED: Retrospective record review of dogs that underwent surgery to remove histologically diagnosed conjunctival HA or HSA between April 2004 and April 2020 to collect data on signalment, tumor location, interval between initial presentation and surgery, tumor diagnosis, surgical dose, surgical margins, tumor size, recurrence and survival times. RESULTS: A total of 52 dogs (60 tumors) were included. The mean age of affected dogs was 8.69 years; the most affected breed was the Border collie (n = 13, 25%). 28 tumors were HA (46.67%) and 32 HSA (53.33%). Tumors occurred in three locations: the lateral bulbar conjunctiva (n = 37, 61.67%), the third eyelid margin (n = 19, 31.67%), and the ventral conjunctival fornix (n = 4, 6.67%). There was no site predilection for HA versus HSA. 97% of tumors occurred in non-pigmented tissue. Corneal invasion was more likely to be a feature of malignant tumors. Five tumors were incompletely excised, one of which recurred. There was no statistical difference in likelihood of incomplete excision between HSA and HA. Six tumors (10%) recurred. HSA was not statistically more likely to recur than HA. Recurrence times ranged from 5 weeks to 1 year. CONCLUSION: Surgical treatment of conjunctival HA and HSA is likely to be curative. There is a recurrence rate of 10% regardless of tumor type, and recurrence may be late in the course of the disease.

Serum angiopoietin-2 levels in dogs with splenic haemangiosarcoma, haemangioma, and splenitis.

Haemangioma (HA) and haemangiosarcoma (HSA) are among the most common splenic neoplasms in dogs. The survival time in splenic HSA is short, probably due to the lack of proper biological markers allowing early detection. We investigated the serum angiopoietin-2 (Ang-2) concentrations in 9 healthy dogs and 40 dogs with abnormal splenic masses. The Ang-2 concentration differences were further compared in healthy dogs, dogs with splenitis, splenic HA and HSA. The results showed that the Ang-2 level in healthy dogs was significantly lower than in the splenitis and splenic HA cases. Moreover, the Ang-2 level was significantly higher in splenic HA than in splenic HSA. Conversely, no significant differences in Ang-2 level were recorded between healthy and splenic HSA dogs, and between splenitis and splenic neoplasms (HA and HSA). No significant correlations were observed between the Ang-2 level and (i) the clinical stage, (ii) histological growth pattern, and (iii) median survival time of splenic HSA dogs. In conclusion, serum Ang-2 concentration is a potentially useful biological marker for the discrimination of dogs with splenitis and splenic HA, as well as for the differentiation of splenic HA from its malignant form, HSA.

A Review of Proliferative Vascular Disorders of the Central Nervous System of Animals.

In disease, blood vessel proliferation has many salient roles including in inflammation, when granulation tissue fills superficial defects, or in the recanalization of an occluded blood vessel. Sometimes angiogenesis goes awry-granulation can be exuberant, and plexiform proliferation of vascular components can contribute to pulmonary hypertension. This review focuses on the diverse manifestations of pathologic vascular overgrowth that occur in the brain, spinal cord, and meninges of animals from birth until old age. Entities discussed include systemic reactive angioendotheliomatosis in which glomeruloid vascular proliferations are encountered in various organs including the central nervous system (CNS). The triad of CNS vascular malformations, hamartomas, and benign vascular proliferations are an especially fraught category in which terminology overlap and the microscopic similarity of various disorders makes diagnostic classification incredibly challenging. Pathologists commonly take refuge in "CNS vascular hamartoma" despite the lack of any unique histopathologic features and we recommend that this diagnostic category be abandoned. Malformative lesions that are often confusing and have similar features; the conditions include arteriovenous malformation, cavernous angioma, venous angioma, and capillary telangiectases. Meningioangiomatosis, a benign meningovascular proliferation with dual components, is a unique entity seen most commonly in young dogs. Last, accepted neoplastic conditions range from lower-grade locally acquired growths like hemangioblastoma (a tumor of mysterious interstitial stromal cells encountered in the setting of abundant capillary vasculature proliferation), the rare hemangioendothelioma, and the highly malignant and invariably multifocal metastatic hemangiosarcoma. Additionally, this review draws on the comparative medical literature for further insights into this problematic topic in pathology.

Canine cutaneous neoplasms in the metropolitan region of Goiânia, Goiás state, Brazil / Neoplasias cutâneas caninas na região metropolitana de Goiânia, Goiás, Brasil

ABSTRACT: The present study aimed to describe the occurrence and epidemiological features of skin neoplasms diagnosed in dogs in the metropolitan region of Goiânia, Goiás state, Brazil. Diagnoses from dog biopsies from 2011 to 2016 provided by a private veterinary pathology laboratory were analyzed. The main diagnoses were mast cell tumor, hemangiosarcoma, squamous cell carcinoma, malignant melanoma, and hemangioma. Highest frequency of neoplasms was found in female dogs, dogs aged > 8 years, and purebred dogs, particularly the American Pit Bull Terriers and the Poodles. Most common sites affected by the neoplasms were the limb and the head. Using multiple correspondence analysis, groups of neoplasms were found to be associated with different epidemiological features and the size of the neoplasms was associated with the biological behavior. The results of this study described predispositions and verified the importance of different types of skin neoplasms in dogs in the region being studied.(AU)

O objetivo deste estudo foi determinar a prevalência e as características epidemiológicas das neoplasias cutâneas em cães na região metropolitana de Goiânia, Goiás. Foram analisados os diagnósticos de um laboratório do setor privado de 2011 a 2016. Mastocitoma, hemangiossarcoma, carcinoma de células escamosas, melanoma maligno e hemangioma representaram os principais diagnósticos. A maioria dos casos ocorreram em cães de raças definidas, fêmeas e com idade >8 anos. American Pit Bull Terrier e Poodle foram as raças mais encontradas. As neoplasias acometeram principalmente regiões de membros e cabeça. Pela análise de correspondência múltipla, associou-se os grupos de neoplasias com diferentes características epidemiológicas e o tamanho da neoplasia com o comportamento biológico. A comparação dos resultados com pesquisas prévias possibilitou confirmar predisposições previamente descritas e verificar a importância dos diferentes tipos de neoplasias cutâneas em cães na região estudada.(AU)

Immunohistochemical detection of p53 and pp53 Ser392 in canine hemangiomas and hemangiosarcomas located in the skin.

BACKGROUND: p53 protein is essential for the regulation of cell proliferation. Aberrant accumulation of it usually occurs in cutaneous malignancies. Mutant p53 is detected by immunohistochemistry because it is more stable than the wild-type p53. However, post-translational modifications of p53 in response to ultraviolet radiation are important mechanisms of wild-type p53 stabilization, leading to positive staining in the absence of mutation. The aims were: 1) to analyze the immunohistochemical expression of p53 and phospho-p53 Serine392 in canine skin endothelial tumours; and 2) to determine if any relationship exists between p53 and phospho-p53 Serine392 overexpression and cell proliferation. RESULTS: p53 and phospho-p53 Serine392 immunolabeling was examined in 40 canine cutaneous endothelial tumours (13 hemangiomas and 27 hemangiosarcomas). Their expression was associated with tumour size, hemangiosarcoma stage (dermal versus hypodermal), histological diagnosis and proliferative activity (mitotic count and Ki-67 index). Statistical analysis revealed a significant increase of p53 immunoreactivity in hemangiosarcomas (median, 74.61%; interquartile range [IQR], 66.97-82.98%) versus hemangiomas (median, 0%; IQR, 0-20.91%) (p < .001) and in well-differentiated hemangiosarcomas (median, 82.40%; IQR, 66.49-83.17%) versus hemangiomas (p = .002). Phospho-p53 Serine392 immunoreactivity was significantly higher in hemangiosarcomas (median, 53.80%; IQR, 0-69.50%) than in hemangiomas (median, 0%; IQR, 0.0%) (p < .001). Positive correlation of the overexpression of p53 and phospho-p53 Serine392 with mitotic count and Ki-67 index was found in the cutaneous vascular tumours (p < .001). The Ki-67 index of the hemangiomas (median, 0.50%; IQR, 0-2.80%) was significantly lower than that of the hemangiosarcomas (median, 34.85%; IQR, 23.88-42.33%) (p < .001), and that specifically of well-differentiated hemangiosarcomas (median, 24.60%; IQR, 15.45-39.35%) (p = .001). Immunolabeling of 18 visceral hemangiosarcomas showed that the p53 (median, 41.59%; IQR, 26.89-64.87%) and phospho-p53 Serine392 (median, 0%; IQR, 0-22.53%) indexes were significantly lower than those of skin (p = .001; p = .006, respectively). CONCLUSIONS: The p53 and phospho-p53 Serine392overexpression together with high proliferative activity in hemangiosarcomas versus hemangiomas indicated that p53 might play a role in the acquisition of malignant phenotypes in cutaneous endothelial neoplasms in dogs. The Ki-67 index may be useful in distinguishing canine well-differentiated hemangiosarcomas from hemangiomas.

Remission after complete excision of an intramedullary hemangioma with an identifiable tumor plane in a dog.

OBJECTIVE: To describe the use of an identifiable tumor plane (ITP) during myelotomy to excise an intramedullary hemangioma in a dog and report the outcome. STUDY DESIGN: Case report. ANIMALS: One 5.5-year-old 42.9-kg spayed female Leonberger dog. METHODS: Clinical signs included progressive proprioceptive deficits of both pelvic limbs. Magnetic resonance imaging was consistent with a dorsal intramedullary mass at L3-L4. A laminectomy of the third and fourth lumbar vertebrae provided access for dorsal myelotomy. A clear surgical ITP was identified between the intramedullary mass and the spinal cord facilitating complete surgical resection. RESULTS: Histopathological examination was consistent with a hemangioma. Postoperative MRI was consistent with complete excision of the mass. No evidence of recurrence was found by MRI at 3 months and at 22 months after surgery. Mild proprioceptive deficits persisted in the right pelvic limb. CONCLUSION: A clear ITP was present, and gross-total resection (GTR) was achieved without significant morbidity. Persistent clinical remission resulted from surgery as the sole therapy. CLINICAL SIGNIFICANCE: For an intramedullary tumor, GTR is the absence of visible tumor on intraoperative inspection combined with the absence of intramedullary contrast enhancement on postoperative MRI. When an ITP is present, GTR and resultant long-term remission may be more likely.

Clinical features of canine pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BACKGROUND: Histologic features of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) have been described in dogs but without a thorough clinical description. OBJECTIVES: To report the clinical features, diagnostics, treatment, and outcome of dogs with histologic evidence of PVOD and PCH. ANIMALS: Fifteen pet dogs meeting histopathologic criteria of PVOD (occlusive remodeling of small-sized to medium-sized pulmonary veins) or PCH (alveolar capillary proliferation and congestion), or both. METHODS: Medical records of dogs with PVOD and PCH identified based on histopathologic features between 2003 and 2017 were retrospectively reviewed. RESULTS: Fifteen dogs met inclusion criteria of a histologic diagnosis of PVOD or PCH or both. Dogs were older (median 11 years) with no apparent breed or sex predisposition. Dogs presented with acute clinical signs (median 3 days), usually respiratory distress. Thoracic radiography (available in 10 dogs) revealed right cardiomegaly and patchy or diffuse interstitial to alveolar patterns, with 9 dogs having a normal left cardiac silhouette. In 5 dogs tested, pulmonary arterial hypertension (PAH) was documented. In all 3 dogs, thoracic computed tomography scans showed pulmonary arterial enlargement and perivascular diffuse nodular ground-glass opacities. Ten of 15 dogs died within 1 day; median survival was 3 days. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with PAH, the inability to document left-sided congestive heart failure and failure to identify another cause of signs of respiratory disease should increase suspicion for PVOD and PCH. With increased awareness of PVOD and PCH by clinicians and pathologists, dogs with compatible clinicopathologic features should be evaluated for these pulmonary vascular disorders.

Isolation and characterization of subgroup J Avian Leukosis virus associated with hemangioma in commercial Hy-Line chickens.

There was an outbreak of hemangioma associated with avian leukosis virus subgroup J (ALV-J) between 2006 and 2010 in China in commercial layer chickens. Recently, severe hemangiomas broke out in Hy-Line layer chickens on a poultry farm in 2017 where ALV was eradicated earlier. Six isolates of ALV-J, named SDAU1701-SDAU1706, were characterized by virus isolation and sequence analysis of the complete proviral genomes. Avian leukosis virus subgroup J was identified by an immunofluorescence assay with monoclonal antibody JE9, whereas Marek's disease virus or reticuloendotheliosis virus was not detected. Sequence analysis of the complete proviral genome revealed that there was 96.0-99.6% identity between each other and had a homology of 94.6-96.0% when compared with the reference strain. The six isolates formed one distinct lineage separate from the reference sequences in a phylogenetic-tree, which suggested that there were several genetic differences between these groups. Homology analysis of the env, pol, and gag genes of the six isolates showed that the env gene was more variable, especially the gp85 protein, which shared only 88.2-91.9% identity with the reference strains. Sequence comparisons of the gp85 protein indicated that 19 sites were different from those in the NX0101 and HPRS-103 strains inducing myeloid leukosis; among our strains, five mutations were identical to those in the viruses causing hemangioma. Four other distinctive mutations were detected in our six isolates. This study reminds us that the surveillance of viral eradication should be conducted continuously on a farm where ALVs were eradicated. To prevent the prevalence of ALVs, more attention should be paid to daily monitoring.

Angioceratoma conjuntival canino: relato de caso / Canine conjunctival angiokeratoma: case report

O angioceratoma é um tumor de origem vascular, semelhante ao hemangioma, que se diferencia deste por alterações histológicas epiteliais. A apresentação ocular do angioceratoma é pouco frequente em cães, sendo mais comum a ocorrência de hemangioma e hemangiossarcoma. Neste relato, é descrito o caso de um cão, macho, da raça Border Collie, que apresentava uma massa localizada, hiperêmica, bem vascularizada e protrusa, na região temporal da conjuntiva bulbar do olho direito (OD). Foi realizado exame oftalmológico completo e ultrassonografia ocular, tendo sido possível observar que a massa não envolvia outras estruturas oculares além da conjuntiva. Dessa forma, foi realizada a conjuntivectomia parcial, e o material foi encaminhado para análise histológica. O exame histopatológico foi conclusivo para um angioceratoma e mostrou que as margens da amostra estavam livres. O procedimento cirúrgico com margem de segurança foi eficiente no tratamento da neoplasia, sem recorrência até o momento do presente relato.(AU)

Angiokeratomas have been described as tumors of vascular origin, similar to hemangioma but with participation of adjacent epithelium and less frequent in dogs. In this case we have reported an adult, male, Border Collie dog presenting a localized and hyperemic mass with protrusion surface and well vascularized region of temporal bulbar conjunctiva of the right eye (OD). Complete ocular examination and ocular ultrasound have revealed no involvement of other ocular structures beyond the conjunctiva. A partial conjuntivectomy was surgically performed, tissue material sent for histological analysis and angiokeratoma diagnosis was accurately made. Surgical procedure with a safety tissue margin has shown adequate treatment efficiency, with no neoplasia recurrence to date.(AU)

Gp85 genetic diversity of avian leukosis virus subgroup J among different individual chickens from a native flock.

To compare the genetic diversity and quasispecies evolution of avian leukosis virus (ALV) among different individuals, 5 chickens, raised in Shandong Provice of China, were randomly selected from a local chicken flock associated with serious tumor cases. Blood samples were collected and inoculated into chicken embryo fibroblast and DF-1 cell lines for virus isolation and identification, respectively, of Marek's disease virus (MDV), reticuloendotheliosis virus (REV), and ALV. Five strains of ALV subgroup J (ALV-J) were identified, and the gp85 gene from each strain was amplified and cloned. For each strain, about 20 positive clones of gp85 gene were selected for sequence analyses and the variability of the quasispecies of the 5 strains was compared. The results showed that the nuclear acid length of gp85 gene of 5 ALV-J isolates is 921 bp, 921 bp, 924 bp, 918 bp, and 912 bp respectively, and amino acid homologies of different gp85 clones from the 5 ALV-J strains were 99.3 to 100%, 99.3 to 100%, 99.4 to 100%, 98.4 to 100%, 99.0 to 100%, respectively. The proportions of dominant quasispecies were 65.0%, 85.0%, 85.0%, 50.0%, 84.2%, respectively, and homology of the gp85 among these dominant quasispecies was 89.2 to 92.5%. These data demonstrated the composition of the ALV-J quasispecies varied among infected individuals even within the same flock, and the dominant quasispecies continued to evolve both for their proportion and gene mutation.

Immunohistochemical Detection of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor in Canine Vascular Endothelial Tumours.

Immunohistochemistry was used to assess the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in 57 canine primary haemangiosarcomas (HSAs), 26 canine cutaneous haemangiomas (HAs) and in control sections of canine cutaneous granulation tissue. The correlation between uPA/uPAR expression and the Ki67 labelling index (LI) was estimated in the HSA and HA tissues. uPA was expressed by 73.2% and 75.0% of splenic HSAs and non-splenic HSAs, respectively. All HSA tissues tested expressed uPAR. Expression of both molecules was significantly higher in HSAs than in cutaneous HAs (3.8% for uPA and 30.7% for uPAR). The average Ki67 LI of the uPA(+)/uPAR(+) HSAs was significantly higher than that of uPA(-)/uPAR(+) HSAs and HA tissues (mean ± SDs 32.8 ± 15.3, 15.2 ± 7.2 and 2.1 ± 0.7, respectively; P <0.05). These results suggest that uPA and uPAR play a significant role in the malignant proliferation of canine HSA, regardless of the primary origin of the tumour.

Mutations in and Expression of the Tumor Suppressor Gene p53 in Egg-Type Chickens Infected With Subgroup J Avian Leukosis Virus.

To investigate the molecular mechanisms of the oncogenic effects of avian leukosis virus subgroup J (ALV-J), we examined mutations in and the expression of p53 in the myelocytomas distributed in the liver, spleen, trachea, and bone marrow, as well as in fibrosarcomas in the abdominal cavity and hemangiomas in skin from chickens that were naturally or experimentally infected with ALV-J. Two types of mutations in the p53 gene were detected in myelocytomas of both the experimentally infected and the naturally infected chickens and included point mutations and deletions. Two of the point mutations have not been reported previously. Partial complementary DNA clones with a 122-bp deletion in the p53 gene ORF and a 15-bp deletion in the C-terminus were identified in the myelocytomas. In addition, moderate expression of the mutant p53 protein was detected in the myelocytomas that were distributed in the liver, trachea, spleen, and bone marrow. Mutant p53 protein was not detected in the subcutaneous hemangiomas or in the abdominal fibrosarcomas associated with natural and experimental ALV-J infection, respectively. These results identify mutations associated with abnormal expression of p53 in ALV-J-associated myelocytomas, suggesting a role in tumorigenesis.

Analysis of genomic mutation and immunohistochemistry of platelet-derived growth factor receptors in canine vascular tumours.

We examined whether mutation of the platelet-derived growth factor receptor protein tyrosine kinase (PDGFR)-α and PDGFR-ß genes contributes to their overexpression in canine vascular tumours. Genomic sequences of trans- or juxtamembrane regions of PDGFR-α and PDGFR-ß were analysed with immunohistochemical staining and polymerase chain reaction-direct sequencing using DNA from paraffin-embedded neoplastic tissues of 27 hemangiosarcomas (HSAs) and 20 hemangiomas (HAs). Immunohistochemically, 75% of the HA cases were positive for PDGFR-α and almost most of the HA cases were negative for PDGFR-ß. Of the HSA cases, 55.6% were negative for PDGFR-α and 63% were strongly positive for PDGFR-ß. Among the HA cases, 1 missense mutation was detected in PDGFR-α exon 18 and 1 in PDGFR-ß exon 17. Two HSA cases had missense mutations in exon 14 and 1 in exon 17 of PDGFR-ß. Thus, genomic mutation of trans- or juxtamembrane regions of PDGFRs was not the main mechanism driving the activation of receptors in HSA and HA.