ABSTRACT
Oral malignant melanoma (OMM) is the most common canine melanocytic neoplasm. Overlap between the somatic mutation profiles of canine OMM and human mucosal melanomas suggest a shared UV-independent molecular aetiology. In common with human mucosal melanomas, most canine OMM metastasise. There is no reliable means of predicting canine OMM metastasis, and systemic therapies for metastatic disease are largely palliative. Herein, we employed exon microarrays for comparative expression profiling of FFPE biopsies of 18 primary canine OMM that metastasised and 10 primary OMM that did not metastasise. Genes displaying metastasis-associated expression may be targets for anti-metastasis treatments, and biomarkers of OMM metastasis. Reduced expression of CXCL12 in the metastasising OMMs implies that the CXCR4/CXCL12 axis may be involved in OMM metastasis. Increased expression of APOBEC3A in the metastasising OMMs may indicate APOBEC3A-induced double-strand DNA breaks and pro-metastatic hypermutation. DNA double strand breakage triggers the DNA damage response network and two Fanconi anaemia DNA repair pathway members showed elevated expression in the metastasising OMMs. Cross-validation was employed to test a Linear Discriminant Analysis classifier based upon the RT-qPCR-measured expression levels of CXCL12, APOBEC3A and RPL29. Classification accuracies of 94% (metastasising OMMs) and 86% (non-metastasising OMMs) were estimated.
Subject(s)
Dog Diseases/genetics , Gene Expression Regulation, Neoplastic , Genome-Wide Association Study/methods , Melanoma/genetics , Mouth Mucosa/metabolism , Mouth Neoplasms/genetics , Animals , Chemokine CXCL12/genetics , Chemokine CXCL12/metabolism , Cytidine Deaminase/genetics , Cytidine Deaminase/metabolism , DNA Breaks, Double-Stranded , DNA Repair/genetics , Dog Diseases/metabolism , Dogs , Female , Gene Expression Profiling/methods , Male , Melanoma/metabolism , Melanoma/pathology , Mouth Mucosa/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Neoplasm Metastasis , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolismABSTRACT
OBJECTIVES: To evaluate the effect of syringe size, needle size, number of needle passes and operator experience on cell yield from tumour fine-needle aspirates, and the quantity and quality of extractable RNA. MATERIALS AND METHODS: Fine-needle aspirates were collected from canine lymphoma, cutaneous mast cell tumour, anal gland adenocarcinoma, fibrosarcoma and oral malignant melanoma using nine different techniques. RESULTS: There was a significant difference in cell yield between fine-needle aspirate techniques for melanoma, lymphoma and anal gland adenocarcinoma. The application of suction yielded the largest number of cells. Cell numbers in lymphoma and fibrosarcoma aspirates collected by different veterinary surgeons were not significantly different. Use of a smaller gauge needle and suction increased the quantity of RNA isolated from fibrosarcoma and anal gland adenocarcinoma aspirates, but did not influence RNA integrity. CLINICAL SIGNIFICANCE: Suction during fine-needle aspiration increases cell numbers obtained from five common canine tumours. Suction increases the quantity of RNA isolated from anal gland adenocarcinoma and fibrosarcoma aspirates without affecting RNA quality. Junior veterinary surgeons gain comparable cell numbers to senior staff.
Subject(s)
Biopsy, Fine-Needle/veterinary , Neoplasms/veterinary , RNA, Neoplasm/isolation & purification , Animals , Biopsy, Fine-Needle/instrumentation , Biopsy, Fine-Needle/methods , Cell Count/veterinary , Dogs , Health Knowledge, Attitudes, Practice , Humans , Needles , Neoplasms/genetics , Neoplasms/pathology , Professional Competence , Specimen HandlingABSTRACT
CASE DESCRIPTION: A nearly 6-year-old female spayed Labrador Retriever was presented for acute abdominal pain and lethargy. The dog had no previous health concerns apart from occasional episodes of urinary incontinence in the 2 months prior to presentation. A retroperitoneal mass involving the right ureter was found during the investigations. Serum urea was mildly elevated, but the serum creatinine was within the normal range. No distant metastases were detected. A right ureteronephrectomy was performed. The ureteral mass was confirmed as a leiomyosarcoma and completely excised. The kidney was histologically normal. Unfortunately, during a routine 3-month postoperative assessment, a recurrent mass at the previous retroperitoneal surgical site was confirmed by biopsy to be a leiomyosarcoma. Courses of doxorubicin and chlorambucil were given, but failed to halt the progression of the recurrent mass. The dog was euthanised 5.5 months postoperatively because of poor quality of life. CLINICAL RELEVANCE: Ureteral leiomyosarcoma should be on the differential diagnosis list for a retroperitoneal mass, possibly causing severe abdominal pain with minor clinical signs associated with the urinary tract. This dog in this reported case of ureteral leiomyosarcoma had a short survival time, despite complete surgical excision and chemotherapy, because of local recurrence.
