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Gene expression association study in feline mammary carcinomas

Publication . Ferreira, Daniela; Martins, Bárbara; Soares, Maria; Correia, Jorge; Adega, Filomena; Ferreira, Fernando; Chaves, Raquel

Works on cancer-related genes expression using feline mammary carcinomas (FMCs) are scarce but crucial, not only to validate these tumours as models for human breast cancer studies but also to improve small animal practice. Here, the expression of the cancer-related genes TP53, CCND1, FUS, YBX1, PTBP1, c-MYC and PKM2 was evaluated by real-time RT-qPCR, in a population of FMCs clinically characterized and compared with the disease-free tissue of the same individual. In most of the FMCs analysed, RNA quantification revealed normal expression levels for TP53, c-MYC, YBX1 and FUS, but overexpression in the genes CCND1, PTBP1 and PKM2. The expression levels of these cancer-related genes are strongly correlated with each other, with exception of c-MYC and PKM2 genes. The integration of clinicopathological data with the transcriptional levels revealed several associations. The oral contraceptive administration showed to be positively related with the TP53, YBX1, CCND1, FUS and PTBP1 RNA levels. Positive associations were found between tumour size and YBX1 RNA, and lymph node metastasis with c-MYC RNA levels. This work allowed to verify that many of these cancer-related genes are associated but may also, indirectly, influence other genes, creating a complex molecular cancer network that in the future can provide new cancer biomarkers.

2019-08-28Journal article

Open access

Clinical and molecular characterization of feline mammary carcinomas overexpressing HER2 proto-oncogene (FMC-HER2+) : new strategies for effective diagnostic and cancer therapy

Publication . Silva, Maria João da Costa Soares da; Ferreira, Fernando António Costa; Correia, Jorge Manuel de Jesus

Considering the scarce data available in feline mammary carcinoma (FMC) and despite its importance in veterinary clinical practice, this thesis emerges in order to increase the knowledge of this tumor type, especially the FMC-HER2 positive. In the first two studies, the protocols for detection and quantification of the fHER2 and Ki-67 biomarkers were optimized and validated. These studies demonstrated that, in cats, the incidence of fHER2 overexpression were similar to women (about 30%), although no gene amplification was detected. It was also demonstrated that high levels of Ki-67 index were associated with a worse prognosis. Using a panel of protein biomarkers, the FMC were divided into six different groups that demonstrated prognostic value, similarly to what is described in women. In fact, cats with triple negative basal-like or HER2-positive subtypes were associated with shorter overall survival, contrasting with cats presenting luminal A tumors. Moreover, these studies also indicated that luminal B and triple negative basal-like subtypes are the most common in cats. When the metastatic lesions were evaluated, a marked loss of receptor expression was found, which was associated with an increase of the triple negative basal-like subtype, highlighting the importance of immunophenotyping all lesions (primary and metastatic) in cats. Considering these results, the development of diagnostic methodologies that allows the continuous follow-up of the patients would be very useful. Therefore, the last study presented in this thesis evaluates the fHER2 serum levels in cats with FMC using two different immunoassays (ELISA and dot blot). The serum levels of fHER2 were significantly associated with the fHER2 in tissue samples of FMC (assessed by IHC). This is consistent to what is described for humans and suggests that serum quantification could be an important tool for monitoring cats after the surgery. In sum, the results presented herein provide new diagnostic and prognostic tools for veterinary oncology. Considering the high prevalence and similarities with the human counterpart, cat can also represent a potential animal model for the study of luminal B and triple negative subtypes. Considering fHER2-positive FMC more studies are required in order to determine the aetiology of the protein overexpression.

2016-07-04Doctoral thesis

Open access