St Gallen molecular subtypes in feline mammary carcinoma and paired metastases—disease progression and clinical implications from a 3-year follow-up study
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Considering that scarce data are available on disease progression of feline mammary carcinoma (FMC), this study aimed to analyze the clinical, pathological, and immunophenotypic features collected from 61 queens with FMC and to compare the concordance ratios of the expression levels of five molecular markers (ER, PR, fHER2, CK5/6, and Ki-67) between primary tumors (PT) and metastatic lesions. The results showed that cats with luminal A mammary carcinomas (MC) had higher overall survival (924.6 days, p = 0.001) and longer disease-free period (385.4 days, p = 0.005) compared to the ones with other MC subtypes. In fact, queens with triple negative/basal-like MC showed the lowest survival (mean 156.2 days) and the shortest disease-free survival (mean 28 days) among the molecular subtypes of MC. The lung was the organ most frequently affected by metastases, and animals with lung and/or pleural metastases were more likely to display metastases at three or more locations (p = 0.039). A large heterogeneity in protein expression levels was found between PT and paired metastases, with both estrogen and progesterone receptors more likely to be downregulated in metastases. Paired metastases frequently had higher Ki-67 index than PT, whereas fHER2 overexpression was seen in 46 samples (30 %) and CK5/6 expression was found in 50.7 % of metastases (36/71). Results also revealed that disease progression leads to a high percentage of triple negative/basal-like metastases (9/23; 39.1 %) associated with the absence of luminal A subtype in distant metastases (0/23). This study highlights the prognostic importance of immunophenotyping of MC in cats, although the modified protein expression identified in metastases contributes to justify why possible targeted therapies may fail in some animals with metastatic disease. Altogether, the results obtained also demonstrate that FMC can be used as a model to study human breast cancer.
KeywordsFeline mammary carcinoma Metastatic disease Molecular classification Prognostic biomarkers
This study was supported by “Fundação para a Ciência e Tecnologia” (FCT) through the project CIISA/UID/CVT/00276/2013 and the PhD fellowship (SFRH/BD/70720/2010). The authors would like to thank João Matos and José Cabeçadas (MD) from Instituto Português de Oncologia de Lisboa (IPO); Manuel Mestre (DVM), Ana Mota (DVM, MSc) and Tiago Rafael (DVM, MSc) from the Clínica Veterinária Zoomédica; Mafalda Lage (DVM, MSc) from the Clínica Veterinária Villa Animal; Rafaela Lalanda (DVM, MSc) and Miguel Caninhas (DVM) from the Clínica Veterinária Mvet; Verónica Azevedo (DVM, MSc) from the Hospital Sul do Tejo; and António Ferreira (DVM, PhD), Ana Murta (DVM, MSc) and Rodrigo Bom (DVM) from the Small Animal Hospital from the Faculty of Veterinary Medicine at the University of Lisbon, for the clinical follow-up. We would also like to thank Margarida Simões (DVM, MSc) and Shabir Najmudin (DSc, PhD) from the Faculty of Veterinary Medicine at the University of Lisbon for English language editing.
Compliance with ethical standards
Tumor samples were collected in accordance with the EU Directive 2010/63/EU, and research was approved by the ethics committee of the Faculty of Veterinary Medicine (FVM), University of Lisbon (ULisboa).
Conflicts of interest
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