Academic literature on the topic 'Feline diffuse iris melanoma'

Diffuse iris melanoma was confirmed by light-microscopic examination in 10 formalin-fixed, paraffin-embedded globes from 10 cats. To determine if feline leukemia virus or a replication defective feline leukemia virus, feline sarcoma virus, was present in these anterior uveal melanomas, immunohistochemistry and polymerase chain reaction for feline leukemia virus were utilized. Immunohistochemical staining for feline leukemia virus glycoprotein 70 was performed on all 10 tumors using an avidin–biotin complex technique. The DNA was extracted from each specimen and a 166-base pair region of the feline leukemia virus long terminal repeat was targeted by polymerase chain reaction. Immunohistochemical staining for feline leukemia virus glycoprotein 70 and polymerase chain reaction amplification of a feline leukemia virus long terminal repeat region were negative in all cases. Feline leukemia virus/feline sarcoma virus was not detected in any neoplasms and therefore was unlikely to play a role in the tumorigenesis of these feline diffuse iris melanomas.

Melanocytic neoplasia is the most common form of ocular tumour in cats, accounting for 67% of cases in an analysis of 2614 cases of primary ocular neoplasia. Feline diffuse iris melanoma (FDIM) is by far the most common form of ocular melanocytic neoplasia, with limbal melanomas and atypical melanoma (melanoma affecting the choroid or ciliary body) infrequently recognised. Early lesions begin as flat areas of pigmentation of the iris, known as iris melanosis. This melanosis is a precursor lesion that can become FDIM when pigmented cells infiltrate the anterior iris stroma, commonly alongside a transition in cell morphology. The differentiation between FDIM and benign iris melanosis is only recognisable though histologic examination, with no in vivo means of identifying the malignant transformation. The behaviour of FDIM is variable and difficult to predict. Some FDIM lesions have a more benign progression and can slowly grow or remain static for years without affecting the ocular or systemic health of the individual, whilst other tumours behave aggressively, invading the ocular structures and significantly affecting the life expectancy of cats through metastatic disease. This makes management and timely enucleation of these cases challenging in practice. This article aims to review our current knowledge of FDIM.

Objectives Feline diffuse iris melanoma (FDIM) is the most common malignant primary intraocular tumour in cats, with reported metastases rates between 19% and 63%. Currently, the only available diagnostic tool for a tentative diagnosis is histopathological examination of the enucleated eye. Therefore, the veterinary ophthalmologist is often faced with the dilemma of whether to enucleate an oftentimes visual eye or to continue monitoring, with the risk of metastases developing. In the past, cell-free DNA (cfDNA) gained more attention in human medicine, especially in the field of oncology. Prior studies have shown the use of cfDNA as diagnostic or prognostic markers in canine and human cancer patients. Therefore, the aim of this study was to investigate cfDNA concentration and integrity in cats with FDIMs compared with cats with benign iris naevi and without ocular abnormalities. Methods cfDNA from plasma of cats with iris melanoma (n = 34), iris naevus (n = 30) and without ocular abnormalities (n = 32) were extracted. Primer and probes for feline amyloid beta precursor protein ( APP) and beta actin ( ACTB) were designed for amplicons of various lengths and quantitative PCRs of extracted cfDNA were performed to measure cfDNA concentration and integrity of the plasma samples. Differences of cfDNA concentrations and integrity levels between the three groups (iris melanoma, iris naevi and controls) were analysed using the Mann–Whitney U-test. Results cfDNA concentration and integrity analysis revealed no significant differences between the cats with iris melanoma, iris naevus or the control group ( P >0.01). Cats with metastases showed similar cfDNA concentration and integrity to cats without metastases. Conclusions and relevance cfDNA concentration and integrity seem to be insufficient as a diagnostic or prognostic marker in cats with FDIMs.

AbstractThe iris is the least common site of primary uveal melanoma. The prognosis of iris melanoma is better than that of melanoma of the ciliary body and choroid, but the reason for this difference is unclear. One possible explanation is that iris melanoma is smaller than its posterior segment counterparts at the time of diagnosis. Most iris melanomas are spindle cell types, according to a modified Callender classification system. There is evidence that the proliferation of melanocytes of the anterior iris surface (iris plaque) and diffuse stromal invasion may be risk factors for local recurrence and metastasis, respectively.

The present PhD project investigates animal spontaneous models of non-UV induced melanomas, namely canine oral melanoma and feline iris diffuse melanoma (FDIM), which shares unique similarities in biological behavior with human mucosal melanoma and human iris melanoma, respectively. The project investigates selected markers related to the pathogenesis and prognosis of these tumors, i.e. gene and proteins that have been implicated in the progression and metastasis in human, canine and feline melanomas, such as Leukotriene A4 Hydrolase (LTA4H), Fragile X mental retardation-related protein 1 (FXR1) and matrix-metalloproteinases (MMPs). LTA4H is an enzyme of the arachidonic acid cascade, FXR1 is a RNA binding protein, MMPs a family of proteolytic enzymes of the extracellular matrix. The specific aims of the project are: 1) the validation of anti-FXR1 antibodies in the canine species; 2) the investigation of the expression of LTA4H and FXR1 in canine oral melanoma; 3) the study of FXR1-induced modulation of MMPs in canine oral melanoma; 4) the study of MMPs and tumor-matrix interaction in feline diffuse iris melanoma. 1) Two different commercially available polyclonal anti-human FXR1 antibodies were validated for use in dogs. Western blot experiments highlighted the specificity of cross-reaction. Immunohistochemistry described for the first time the specific distribution of FXR1 protein in canine normal tissues, and then the expression of FXR1 in a pool of canine melanocytic tumors. 2) LTA4H and FXR1 genes and proteins expression was investigated in FFPE canine oral melanomas (histology and immunohistochemistry, n=36, from 32 dogs; RT-PCR, subset n=23; clinical follow-up, subset n=13). ΔCt expression values ranged 0.76-5.11 for LTA4H and 0.22-6.24 range for FXR1 (out of range in 3 cases). The immunohistochemical expression of the proteins was evaluated as IRS-score (percentage of positive cells combined with intensity of the staining). IRS-score of LTA4H and FXR1 proteins did not correlate with the expression of the codifying genes. LTA4H and FXR1 seemed not correlated with the known criteria of malignancy or with the clinical outcome, when available. 3) Since FXR1 belongs to a family of RNA binding protein able to modulate the mRNA coding for the proteolytic enzyme MMP-9, MMP-9 and its inhibitor TIMP-2 were investigated by immunohistochemistry in canine oral melanomas to assess the association of FXR1 with MMP-9 and the association of MMPs activity with the clinical outcome. MMP-9 expression seemed not associated with FXR1 in canine oral melanomas. Anyway, intense levels of MMP-9/TIMP-2 were observed in cases with high expression of FXR1 and with unfavorable clinical outcome in canine oral melanoma. 4) The expression of MMPs in FDIM was investigated. Immunohistochemical expression of MMP-9/TIMP-2 was investigated in 62 FDIM and results were compared with the histological grade and mitotic index. MMP-9 and TIMP-2 were expressed in 77.4% and 71.0% FDIM, respectively. Increasing MMP-9 and TIMP-2 paralleled with high histological grades and high mitotic index.