Histological, Immunohistological, and Ultrastructural Description of Vasculogenic Mimicry in Canine Mammary Cancer

Clemente, M.; Alenza, María Dolores Pérez; Illera, Juan Carlos; Peña, Laura

doi:10.1177/0300985809353167

Cited by 98 publications

(80 citation statements)

References 66 publications

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“…Tumour grading (Table S2) was performed by a veterinary pathologist (A.M.), according to the grading system adapted for canine simple mammary carcinoma by Clemente et al ([60] from an existing human grading system [61]. Before microdissection, the identification of tumour stroma in samples was performed by a veterinary pathologist (A.M.).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Ettlin

Clementi

Amini

et al. 2017

IJMS

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Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry. We found that Col1a1 (Collagen1α1), αSMA (alpha Smooth Muscle Actin), FAP (Fibroblast activation protein), PDGFRβ (Platelet-derived growth factor receptor beta), and Caveolin-1 were significantly upregulated in canine CAS, and the expression of CXCL12 (Stromal cell derived factor 1) significantly decreased, whereas MMP2 (Matrix Metalloproteinase 1) and IL6 (Interleukin 6) did not change. Our results suggest strong similarities in CAS biology in canine and human mammary carcinomas but also reveal some differences. To the best of our knowledge, this is the first report to provide a comprehensive expression analysis of the most important CAS markers in canine simple mammary carcinomas and further supports the validity of the dog as model for human cancer.

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Section: Methodsmentioning

confidence: 99%

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Ettlin

Clementi

Amini

et al. 2017

IJMS

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“…Non-specific binding was blocked by incubation in 5% bovine serum albumin (Sigma Aldrich, Germany). After 30 min, the following primary antibodies (diluted in 1% bovine serum) were used: monoclonal mouse anti-human vimentin, Vim (clone Vim 3B4, Dako, Denmark) diluted 1:50 [17,18], monoclonal mouse anti-human cytokeratin, CK (clone MNF116, Dako, Denmark) diluted 1:50 [17,18], monoclonal mouse anti-human alpha smooth muscle actin, α-SMA (clone 1A4, Dako, Denmark) diluted 1:100 [19], monoclonal mouse anti-human desmin, Des (clone D33, Dako, Denmark) diluted 1:50 [17-19], monoclonal mouse anti-p63 protein (clone 4A4, Santa Cruz Biotechnology, USA) [20], mouse monoclonal anti-human Ki67 (clone MIB-1, Dako, Denmark) diluted 1:75 [15,21,22], rabbit polyclonal anti-human estrogen receptor alpha, ERα (H-184, Santa Cruz Biotechnology, USA) diluted 1:100 [23], ready-to-use mouse monoclonal anti-human progesterone receptor, PR (clone PR10A9, Immunotech, France) [24,25] and rabbit polyclonal anti-human p53 protein (clone FL-393, Santa Cruz Biotechnology, USA) diluted 1:50 [25,26]. The slides were incubated in a humidified chamber for 1 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Retrospective study and immunohistochemical analysis of canine mammary sarcomas

2013

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BackgroundCanine mammary sarcomas (CMSs) are rarely diagnosed in female dogs, which explains the scarcity of immunohistochemical findings concerning those tumors. This paper presents the results of a retrospective study into CMSs and discusses the clinical features of the analyzed tumors, the expression of intermediate filaments CK, Vim, Des and α-SMA, and the expression of p63, Ki67, ERα, PR and p53 protein.ResultsFour percent of all canine mammary tumors (CMTs) were classified as CMSs, and they represented 5.1% of malignant CMTs. The mean age at diagnosis was 11.1 ± 2.8 years. Large breed dogs were more frequently affected (38.7%). The majority of observed CMSs were fibrosarcomas (2.1%). All CMSs expressed vimentin, and higher levels of vimentin expression were noted in fibrosarcomas and osteosarcomas. Ki67 expression was significantly correlated with the grade of CMS.ConclusionsOur results revealed that CMSs form a heterogeneous group, therefore, immunohistochemical examinations could support differential and final diagnosis. Although this study analyzed a limited number of samples, the reported results can expand our knowledge about CMSs. Further work is required in this field.

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“…Tumor emboli are often identified in the dermal lymphatics, although the emboli are not always seen on skin biopsy [1,2]. Furthermore, the high expression levels of angiogenic [3-6], lymphangiogenic [3,7], and vasculogenic mimicry factors [4,8,9] observed in IBC specimens is considered critical to IBC’s metastatic behavior [10,11]. …”

Section: Introductionmentioning

confidence: 99%

Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

et al. 2012

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BackgroundInflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens.Patients and MethodsSpecimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration.ResultsFrom a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01).ConclusionsTo our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to stratify IBC patients into low-risk and high-risk groups for death and relapses. High levels of tumor stromal VEGF-A may be useful for identifying IBC patients who will benefit from anti-angiogenic treatment.

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Histological, Immunohistological, and Ultrastructural Description of Vasculogenic Mimicry in Canine Mammary Cancer

Cited by 98 publications

References 66 publications

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Retrospective study and immunohistochemical analysis of canine mammary sarcomas

Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer

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