Canine oral malignant melanoma: genomic and immunohistochemical approaches to better characterize the metastatic dissemination to the lymph node

Malignant melanoma is the most common malignant tumour of the oral cavity in the dog, with high rate of metastatic dissemination to the regional lymph nodes and distant organs. There is significant overlap in regards of biologic behaviour, histological appearance and genomic alterations between canine and human OMMs. Therefore, the dog is considered a good preclinical model for this deadly tumour. In the first part of this study we aimed to identify genes that are involved in the metastatic dissemination of canine OMMs by microarray mRNA profiling of 4 pairs of primary tumours and their lymph nodal metastases. These genes could represent a future target for the control and hopefully treatment of the metastatic disease. We pointed out the presence of several genes displaying different expression between the primary and the metastatic tumour. In particular, Rac1 seems to play a key role in the dissemination of melanoma cells to the lymph node, most likely due to its regulatory activity of cell motility. In the second part of the study we assessed the potential improvement of detection of lymphatic invasion in canine primary OMMs by using immunohistochemistry for Prox-1, as the detection of lymphatic invasion in a primary tumour is generally considered an unfavourable prognostic factor for several cancers, including human and canine OMMs. We also tried to prove direct correlation between the presence of lymphatic invasion in the primary tumour and regional lymph node metastasis. Our results showed that Prox-1 IHC is not able to enhance detection of lymphatic invasion in the primary site and that the sensitivity of detection of lymphatic invasion in predicting lymph nodal metastasis is low (46.7%), despite high specificity (97%). Finally, we pointed out the presence of interobserver variability in detecting lymphatic invasion in canine primary OMMs, most likely due to interpretative variation.