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1.
This study examined immunohistochemical staining patterns for several meningioma variants involving either the brain or spinal cord of dogs. Formalin-fixed, paraffin-embedded tissue from 15 tumors was obtained. The selected tumor group included seven meningothelial, three transitional, two malignant (anaplastic), one myxoid, one papillary, and one osteomatous meningiomas. Tumors were evaluated for reactivity to the following six immunohistochemical markers: vimentin, pancytokeratin, glial fibrillary acidic protein (GFAP), S100, neuron-specific enolase (NSE), and synaptophysin. Vimentin expression was detected in all meningiomas, and 14 of 15 tumors demonstrated intense vimentin staining in more than 50% of the neoplastic cells. Pancytokeratin expression was present in 11 of 15 neoplasms; however, positive staining frequently was focal and often involved a small percentage of the neoplastic cells. GFAP expression was detected in a single, anaplastic meningioma. Although expression of NSE and S100 was detected in 12 of 25 meningiomas, the intensity of the staining and the percentage of positive neoplastic cells was highly variable. Synaptophysin was uniformly negative. These results will help to establish immunohistochemical profiles for meningiomas that will improve our ability to correctly differentiate these neoplasms of meningeal origin from central nervous system tumors originating from other sites.  相似文献   

2.
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.  相似文献   

3.
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.  相似文献   

4.
Fascin‐1 expression was examined in 9 cutaneous melanocytomas and 47 oral melanomas. The cases were scored on the basis of extent and intensity of staining, and combined scores were calculated. Fascin‐1 expression was observed in 5/9 (56%) melanocytomas and 46/47 (98%) melanomas. The combined score for fascin‐1 was significantly greater in stage III/IV melanomas than in stage I/II melanomas (P < 0.05). In addition, strong fascin‐1 staining was associated with a significantly shortened survival time (P < 0.05). The results of this study suggest that fascin‐1 overexpression correlates with the malignancy of canine melanoma and has the potential to be a new immunohistochemical marker to predict the clinical course of canine melanoma. In addition, targeted therapy for fascin‐1 may represent a new strategy for the treatment of canine melanoma.  相似文献   

5.
Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis.  相似文献   

6.
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.  相似文献   

7.
Chondroitin sulfate proteoglycan-4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), is a membrane-bound chondroitin sulfate proteoglycan highly expressed by human melanoma cells. This phylogenetically conserved tumour antigen plays an important biological role in human melanoma, where it is used as a marker to diagnose forms with unusual characteristics, such as desmoplastic melanoma, and to detect melanoma cells in lymph nodes and peripheral blood, and as a target for immunotherapy because of its restricted distribution in normal tissues. To identify suitable targets to develop novel approaches of treating canine melanoma, CSPG4 was studies to see whether it is expressed in canine malignant melanomas. Immunohistochemical staining of 65 canine malignant melanomas with an anti-human CSPG4-specific antibody detected CSPG4 in 37 cases (56.9%). Positive staining was more frequent, albeit not significantly, in amelanotic compared to melanotic tumours and was statistically associated with tumours having both melanin and the epithelioid histotype. The frequency of CSPG4 expression was similar to that of other melanoma antigens used as diagnostic markers for canine malignant melanoma, such as Melan A and the protein recognized by the PNL2 monoclonal antibody. The results suggest that CSPG4 constitutes a new potential immunohistochemical marker of canine malignant melanoma and may represent an immunotherapeutic target as in humans.  相似文献   

8.
Paired box gene 5 (Pax5) is a widely used B‐cell marker for human and canine non‐Hodgkin's lymphoma (nHL); however, in the literature there is only one case report using Pax5 in a cat B‐cell lymphoma. The purposes of this study were to investigate the expression and detection of B‐cell specific activator protein (BSAP) using a monoclonal anti‐Pax5 antibody in feline nHL (FnHL) tissue samples to evaluate its diagnostic relevance as a B‐cell marker. A total of 45 FnHL samples in 45 cats were evaluated. B‐cell lymphoma was the most common immunophenotype (51.1%) for all the samples and T‐cell the most common immunophenotype (64.3%) for the gastrointestinal (GI) form. Pax5 stained 82.6% of all B‐cell lymphomas and no expression was found in any of the T‐cell lymphomas. Anti‐Pax5 antibody staining in FnHL is similar to that reported in human and canine counterparts and may offer an excellent B‐cell marker in cats.  相似文献   

9.
In this study, 50 cases of canine pemphigus foliaceus and 49 cases of canine superficial pyoderma were examined by immunohistochemical staining for patterns of desmoglein expression. In 31/50 (62%) of pemphigus foliaceus cases, there was an altered staining pattern for desmoglein consisting of distinct clumped deposits at the periphery of keratinocytes and/or dark cytoplasmic staining of acantholytic cells (consistent with internalization of desmoglein). In contrast, desmoglein staining in biopsies from cases of superficial pyoderma was diffusely pale without evidence for clumping or distinct internalization. This study demonstrates that epidermal desmoglein expression is altered in some cases of pemphigus foliaceus in dogs and suggests that immunohistochemical staining for this protein may be useful in diagnosis.  相似文献   

10.
Oral squamous cell carcinoma (OSCC) and canine acanthomatous ameloblastoma (CAA) represent two epithelium‐derived neoplasms that affect the oral cavity of dogs. The expression of cytokeratins (CKs) and calretinin has been previously established in the canine tooth bud and odontogenic tumours. The aim of this study was to characterize the CK and calretinin expression profile of OSCC in comparison to CAA and canine tooth bud tissues. Samples from 15 OSCC and 15 CAA cases, as well as 6 tooth buds and 2 normal gingival tissues were examined. OSCC CK expression was consistent with the CK expression profile of CAA and canine tooth bud tissue. Calretinin was positively expressed in 10 of 15 OSCC cases, with 5 cases demonstrating high staining intensity. Only 2 of 15 CAA cases demonstrated mild‐moderate staining intensity. The statistically significant difference in staining pattern and intensity of calretinin in OSCC and CAA can help distinguish between these two tumour types.  相似文献   

11.
Abstract: The cytologic and histologic features of 2 intracranial and 2 spinal (extramedullary cervical) canine meningiomas were compared. Cerebrospinal fluid analysis in 2 cases revealed mild, mixed cell pleocytosis, primarily composed of small lymphocytes and monocytoid cells, with a moderate increase in total protein concentration. Cytologic features suggestive of meningioma included cells with both epithelial and mes-enchymal characteristics and a tendency towards cell clustering. Tumor location also was useful in making a diagnosis. The 4 meningiomas differed histologically from one another, and included angioblastic, psam-momatous, meningotheliomatous, and microcystic anaplastic types, which conformed to a classification scheme for human meningiomas. The classification scheme could not be applied to cytologic specimens.  相似文献   

12.
Calponin is a 34‐kDa smooth muscle‐specific protein that has been shown to be a highly sensitive marker of myoepithelial cells in canine, feline and human mammary tissue and tumours. The expression of calponin was studied in 15 canine, 32 feline and 28 human simple mammary carcinomas using a monoclonal mouse antihuman calponin antibody and the avidin–biotin peroxidase complex (ABC) immunohistochemical technique. Calponin expression was compared with the expression of cytokeratin 14, a marker of normal mammary myoepithelial cells in the three species. Four different types of calponin‐positive cells were identified: (1) Type 1: cytokeratin‐14‐positive pre‐existing myoepithelial cells forming a continuous layer with images of focal disruptions; (2) Type 2: cytokeratin‐14‐positive isolated nests of fusiform, polygonal or round cells without atypia; (3) Type 3: cytokeratin‐14‐positive atypical cells indistinguishable from non‐reactive atypical cells, which should have never been detected in haematoxylin and eosin‐stained sections and (4) Type 4: cytokeratin‐14‐negative stromal fusiform cells around the neoplastic growth or cell nests, identified as myofibroblasts. Calponin‐negative and cytokeratin‐14‐positive atypical neoplastic cells were observed in three canine, 28 feline and two human carcinomas. The latter were indicative of altered expression of high‐molecular‐weight cytokeratins in luminal epithelial‐type simple carcinomas. Our findings show that calponin is a good marker of myoepithelial cell differentiation in feline, human and, particularly, canine simple carcinomas. The high number (six out of 15) of canine tumours with type 3 cells points to the need of both introducing calponin examination in the routine diagnostic schedule and performing further studies on its prognostic significance.  相似文献   

13.
Meningioma is the most common primary brain tumor in cats, although there are few reports about their pathological features. To investigate the histopathological subtypes and immunohistochemical features including expression of cytokeratin and cell adhesion molecules, 45 cases of feline meningioma were examined. The mean age was 12.5 years (range 6–21 years). No statistically significant sex predilection was observed. Regarding the anatomical location of meningioma, tumors mostly developed in the cerebrum, followed by spinal cord and cerebellum, and multiple meningioma was observed in one cat. Microscopically, linear or focal mineralization was observed in 40 cases and cholesterol cleft was observed in 14 cases. Based on histopathological subtypes, there were 15 fibrous, 22 transitional, 2 meningothelial, 5 atypical, and 1 anaplastic meningiomas. These subtypes are classified into grade 1 (39 cases), grade 2 (5 cases), and grade 3 (1 case). There was no significant difference in the Ki-67 index among histological subtypes or grades. Immunohistochemically, the tumor cells were positive for cytokeratin in 5 cases (12.8%), vimentin in 17 cases (43.6%), E-cadherin in 36 cases (92.3%), β-catenin in 21 cases (53.8%), and N-cadherin in 1 case (2.6%), demonstrating the utility of E-cadherin-immunohistochemistry for the diagnosis of feline meningiomas.  相似文献   

14.
Since companion dogs have the same living environment as humans, they are a good animal model for the study of human diseases; this is especially true of canine spontaneous mammary tumours models. A better understanding of the natural history and molecular mechanisms of canine mammary tumour is of great significance in comparative medicine. Here, we collected canine mammary tumour cases and then assayed the clinical cases by pathological examination and classification by HE staining and IHC. miRNA‐497 family members (miR‐497, miR‐16, miR‐195 and miR‐15) were positively correlated with the breast cancer marker genes p63 and PTEN. Modulation of the expression of miR‐497 in the canine mammary tumour cell lines CMT1211 and CMT 7364 induced apoptosis and inhibited cell proliferation. Mechanistically, IRAK2 was shown to be a functional target of miR‐497 that affects the characteristics of cancer cells by inhibiting the activity of the NF‐κB pathway. Overall, our work reveals the miR‐497/IRAK2/NF‐κB axis as a vital mechanism of canine mammary tumour progression and suggests this axis as a target in breast cancer.  相似文献   

15.
Olfactory neuroblastoma (ONB) is a rare intranasal neoplasm in both dogs and humans. Similar clinical presentation and overlapping histologic and immunohistochemical features of ONB with other intranasal neoplasms can make diagnosis and treatment of intranasal neoplasia challenging. Furthermore, in part because of their rarity, there is a lack of reporting on therapeutic regimen for these neoplasms. In humans, initial debulking surgery is usually followed by radiation therapy. Here we report on the histologic, immunohistochemical, and ultrastructural characteristics of canine ONB and report on the clinical progression of cases treated with radiation therapy. In all nine canine ONB examined here, neoplastic cells were arranged in a lobular manner amidst a prominent neurofibrillary matrix and had features consistent with Grade III (high grade) ONB. The neoplastic cells demonstrated positive immunohistochemical staining for TuJ‐1, a Class III beta‐tubulin neuronal cytoskeletal protein, and variable staining for other markers, including chromogranin, synaptophysin, AE1/AE3 and MAP2. The longest surviving case was treated with a regimen similar to that used in humans, consisting of debulking surgery followed by definitive radiation therapy. Our study found that TuJ‐1 is a useful marker for ONB and that radiation therapy, even in cases of advanced disease, may result in prolonged survival.  相似文献   

16.
Tumor cell invasion into the surrounding nervous tissue is one of the histologic hallmarks of anaplastic meningiomas. To identify other possible markers for aggression in canine meningiomas, the relationship between histologic features and the expression of molecules involved in cell adhesion, cell proliferation, and invasion was examined. Immunohistochemistry for epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), β-catenin, doublecortin (DCX), and Ki-67 was performed for 55 cases of canine meningioma. DCX was preferentially expressed in tumor cells invading the brain parenchyma (12 of 14 cases), suggesting its involvement in the invasion process. Regardless of the histologic type, E-cadherin and N-cadherin expression was observed in 31 of 55 and 44 of 55 cases, respectively. There was a significant positive correlation between DCX and N-cadherin expression and a significant negative correlation between E-cadherin and N-cadherin expression, suggesting that decreased E-cadherin and increased N-cadherin expression induce DCX expression. Typical membranous β-catenin expression was observed in 10 of 55 cases, whereas nuclear translocation was observed in 33 cases. Nuclear β-catenin expression was frequently found in anaplastic meningiomas (12 of 14 cases). The Ki-67 labeling indices were significantly higher in anaplastic meningiomas than in other types. These findings indicate that the expression of N-cadherin and DCX and the nuclear translocation of β-catenin are closely associated with the presence of invasion and anaplasia in canine meningiomas. Notably, granular cell meningiomas were negative for almost all the molecules examined, suggesting that they have a different tumor biology than other meningiomas.  相似文献   

17.
Immunohistochemical staining was performed on seven canine and 10 feline soft tissue tumours histologically diagnosed as malignant fibrous histiocytomas (MFHs) or MFH-like tumours, and eight other histologically specified tumours (non-MFH). This was done to determine if commercially available antibodies that are used routinely in human diagnostic pathology for MFHs would express the same immunohistochemical patterns in canine and feline MFHs and MFH-like tumours. The antibodies were directed against human alpha 1-anti-trypsin (AT), human alpha 1-anti-chymotrypsin (ACT), human lysozyme, bovine S-100 protein and human desmin. AT did not show any immunoreactivity in the tissues investigated. Except for one MFH, all canine MFHs and other soft tissue tumours with a 'histiocytic' character stained for lysozyme and not for S-100. Six out of seven canine MFHs and MFH-like tumours stained positive for desmin as did most non-MFH sarcomas. Most of the canine and feline MFHs and MFH-like tumours were positive for ACT. These findings for ACT staining in canine and feline MFHs and MFH-like tumours are in agreement with the findings in human MFHs. The immunohistochemical results of canine MFHs and MFH-like tumours were different from those in cats. Feline MFHs differed from canine MFHs for both lysozyme and desmin staining.  相似文献   

18.
The purpose of this study was to characterize canine prostate cancer using immunohistochemical staining specific for acinar and urothelial/ductal tissue and correlate these results with the dogs' castration status/castration time. Seventy dogs with prostate cancer were included, 71% were castrated and 29% were intact. Compared with an age‐matched control population, castrated dogs were at increased risk of prostate cancer, odds ratio 3.9. Immunohistochemical staining was performed on 58 cases. Forty‐six of the 58 stained positive for cytokeratin 7 (CK 7) (ductal/urothelial origin) and one of the 58 stained positive for prostate‐specific antigen. Dogs with CK 7‐positive tumours were younger when castrated than dogs with CK 7‐negative tumours, 2 versus 7 years (P = 0.03); dogs castrated at ≤2 years of age were more likely to be CK 7‐positive (P = 0.009). These results show that most canine prostatic carcinomas are of ductal/urothelial, androgen‐independent origin. This is consistent with the epidemiological findings, showing increased risk in castrated dogs. Canine prostate cancer may, therefore, not be a realistic model for the human disease.  相似文献   

19.
Follicular lymphomas (FLs) typically exhibit a chromosome translocation that induces constitutive expression of the anti‐apoptotic bcl2 protein and accumulation of additional molecular defects. This rearrangement offers a promising therapeutic target, but its nature as a fundamental driver of FL pathogenesis remains unclear as 15% of cases lack the translocation. We performed an integrated immunohistochemical and genomic investigation of 10 naturally occurring FL cases from domestic dogs, showing that, as with human tumours, they exhibit marked heterogeneity in the frequency and intensity of bcl2 protein expression. Genomic copy number aberrations were infrequent and broadly consistent with those of other canine B‐cell lymphoma subtypes. None of the canine FL specimens exhibited a rearrangement consistent with the hallmark translocation of human FL, despite their remarkable histomorphologic similarity. Parallel exploration of canine and human cases may reveal alternative tumour‐initiating mechanisms other than BCL2 disruption, yielding a more complete definition of the molecular pathogenesis of FL.  相似文献   

20.
Cytogenetic detection of unbalanced genomic aberrations in tumours is a strategy for the identification of tumour suppressor genes and oncogenes. When considered in concert with clinical data, the approach also represents a means of identifying markers of prognosis. In a preliminary investigation of the molecular basis of canine meningioma tumorigenesis, we profiled three tumours by comparative genomic hybridization. Distinct patterns of sub-chromosomal deletions were identified suggesting alternative mechanisms of tumour initiation. The deleted chromosomal segments encompass two regions (10q23.1 and 17q22-q23) that are syntenic to the chromosomes (22 and 1p) most often deleted in human meningiomas. A number of genes associated with DNA repair, cell cycle progression and apoptosis are located on both the deleted canine chromosomal segments and the syntenic regions deleted in human meningiomas. This study represents the first report of chromosomal copy number abnormalities in non-cultured canine brain tumour tissue.  相似文献   

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