Lack of Prognostic Significance of Angiogenesis in Canine Melanocytic Tumours

Cuitiño, Maria C.; Massone, Adriana Raquel; Idiart, Julio Roberto

doi:10.1016/j.jcpa.2012.02.001

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…In our results, VEGF intensity was associated with several clinicopathological variables that reflect tumour aggressiveness, such as the presence of junctional activity, necrosis and ulceration. Microvessel density, assessed by immunohistochemical staining with factor VIII, also named the von Willebrand factor, has been shown to be valuable in distinguishing cutaneous melanomas from melanocytomas, but there is disagreement on its value as a prognostic indicator [34,35]. In our results, associations between COX-2 grade or intensity and factor VIII microvessel density were Bonferroni post-hoc test, where different letters indicate statistically different means.…”

Section: Discussionmentioning

confidence: 63%

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

et al. 2016

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Cyclooxygenase-2 (COX-2) is known to be involved in tumour progression and has been suggested as a therapeutic target in many human and animal malignancies. A number of different pathways subjacent to cancer hallmarks are considered to be involved in COX-2-mediated tumour progression, although these are still largely undefined. Our aim is to investigate associations between COX-2 expression and angiogenesis, proliferation and the inflammatory microenvironment in canine melanocytic tumours. Understanding the involvement of COX-2 with cancer hallmarks might enable us to adapt therapeutic strategies for canine melanomas, an aggressive and often lethal malignancy with value in comparative oncology. Immunohistochemical staining of COX-2, Ki-67 (proliferation index), vascular endothelial growth factor (VEGF), factor VIII (microvessel density), CD3 (lymphocytes) and MAC387 (macrophages) was performed in 51 melanocytic tumours (31 malignant melanomas, 20 melanocytomas). Statistical associations between COX-2 and the other parameters detected were analysed. In melanocytic tumours (n=51), both COX-2 labelling extension and intensity showed a statistically significant association with angiogenesis by factor VIII, VEGF, Ki-67, CD3+ T lymphocytes and MAC387. Within malignant melanomas, COX-2 expression has shown significant associations with microvessel density (factor VIII), lymphocyte and macrophage infiltration and, considering all melanocytic tumours, COX-2 was also associated with VEGF intensity and Ki-67 cell proliferation. Our results point to a role for COX-2 in angiogenesis and in the establishment of an inflammatory microenvironment, favourable to melanoma tumour progression. Further mechanistic studies are warranted to dissect molecular pathways in which COX-2 is involved. Present evidence suggests that COX-2 inhibitors might be useful as an adjuvant treatment to hinder canine melanoma progression.

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Section: Discussionmentioning

confidence: 63%

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

et al. 2016

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“…As far as the predictive role of MVD is concerned, we cannot confirm and direct association, as none of our tumors within a five-year follow-up formed either distant metastasis or relapsed. However, a lack of correlation between MVD and tumor outcome was described in sinonasal, oral and canine melanomas, too [ 14 , 31 ]. In our study, we focused on activated, proliferating endothelium, using antibodies to highlight it—nestin and CD90/Thy1—instead of the widely-used CD31 or CD34 [ 28 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

The Changes of Angiogenesis and Immune Cell Infiltration in the Intra- and Peri-Tumoral Melanoma Microenvironment

Židlík

Brychtová

Uvírová

et al. 2015

IJMS

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Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups—pT1 (35), pT2 (17), pT3 (18) and pT4 (12)—and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries.

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“…MVD seems to be important for diagnostic purposes in canine MT's. MVD is significantly higher in melanoma than in melanocytomas [159] and its expression has been associated with a high mitotic index, necrosis and ulceration (study performed by Gomes J and Pires I, data unpublished). However, its prognostic significance is still discussable [159,160].…”

Section: Microvessel Density (Mvd)mentioning

confidence: 97%

Current Insights Into Canine Cutaneous Melanocytic Tumours Diagnosis

Resende¹,

Moreira²,

Prada³

et al. 2015

Melanoma - Current Clinical Management and Future Therapeutics

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Cutaneous melanocytic tumours are most common in older dogs (mean age of 9 years old) [25], with a higher mean age for dogs with malignant melanocytic tumours (12 years). However, age has not been related with the patient clinical outcome and survival time [26].Although all breeds of dog (and crossbred animals) may be affected, some breeds are reported as predisposed, including Schnauzer, Doberman, Scottish Terrier, Irish Setter, Golden Retriever, Chow Chow, Cocker Spaniel, German Shepherd and Rottweiler [4,27]. Breed predisposition is thought to be related to an underlying genetic risk and/or increased pigmentation in the described above breeds [4].One study [6] has also established a relationship between patient breed and tumour behavior, likely due to genetic susceptibility, as prior described. In the referred work, melanocytic lesions tended to be behaviorally benign in Doberman pinschers and miniature schnauzers, while miniature poodles were the mostly affected breed with malignant melanoma. However, it must be noted that oral neoplasms were also included in that study.An early report described a higher frequency of these lesions in male dogs [28], but recent literature denies gender predisposition [6,27,[29][30][31].

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Lack of Prognostic Significance of Angiogenesis in Canine Melanocytic Tumours

Cited by 4 publications

References 23 publications

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

Investigating associations of cyclooxygenase-2 expression with angiogenesis, proliferation, macrophage and T-lymphocyte infiltration in canine melanocytic tumours

The Changes of Angiogenesis and Immune Cell Infiltration in the Intra- and Peri-Tumoral Melanoma Microenvironment

Current Insights Into Canine Cutaneous Melanocytic Tumours Diagnosis

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