An immunohistochemical study on the expression of sex steroid receptors, Ki-67 and cytokeratins 7 and 20 in feline endometrial adenocarcinomas.
BACKGROUND
Endometrial adenocarcinomas are a rare type of tumour in cats. Though different morphologies have been reported, the most frequent histological type of feline endometrial adenocarcinoma (FEA) is the papillary serous. Characterization of molecular markers expression in FEA may contribute to clarify the pathogenesis of these tumours and to assess the differences between normal endometrium and FEA regarding the expression pattern of several proteins. Therefore, this study aimed to evaluate the immunohistochemical profile of a wide panel of antibodies (specific for ER-α, PR, Ki-67, CK7 and CK20) in twenty-four cases of FEA. Comparisons were made between FEA and feline normal cyclic endometrium in follicular (n = 13) and luteal (n = 10) stages. Except for Ki-67, all other molecular markers were assessed independently for the intensity of immunolabeling and for the percentage of cells expressing the protein.


RESULTS
This study showed that in FEA a loss of expression occurs for ER-α (P ≤ 0.0001) and less markedly also for PR. The lost in sex steroid receptors concerns a decrease in both the proportion of labelled cells and the intensity of immunolabelling (P = 0.002 and P = 0.024, respectively). Proliferative activity, estimated via Ki-67 immunoreaction, significantly increased in FEA as compared to normal endometrium (P ≤ 0.0001). Feline endometrial adenocarcinomas maintained the CK7+/CK20+ status of normal endometrium. However, FEA showed decreased CK7 intensity of labelling compared to normal endometria (P ≤ 0.0001) and loss of CK20 expression, both in intensity (P ≤ 0.0001) and in percentage of positive cells (P = 0.01), compared to normal tissues.


CONCLUSIONS
Data gathered in this study suggest that proliferation in FEA accompanies ER-α down-regulation, possibly following activation of pathways mediated by local growth factors. Moreover, FEA retains combined expression of CK7 and CK20, as evidenced in normal endometrial epithelia, although a decrease in CK7 expression was observed.
CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801, Vila Real, Portugal. analaurasaraiva@gmail.com.|Escola Universitária Vasco da Gama (EUVG), Avenida José R. Sousa Fernandes, Campus Universitário, Bloco B, Lordemão, 3020-210, Coimbra, Portugal. analaurasaraiva@gmail.com.
Ana Laura
AL
Saraiva
CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801, Vila Real, Portugal. rtpayan@gmail.com.
Rita
R
Payan-Carreira
Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313, Porto, Portugal. fgartner@ipatimup.pt.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135, Porto, Portugal. fgartner@ipatimup.pt.
Fátima
F
Gärtner
CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801, Vila Real, Portugal. marta.fortunacunha@gmail.com.
Marta R
MR
Fortuna da Cunha
Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313, Porto, Portugal. alexandra.rema@gmail.com.
Alexandra
A
Rêma
Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313, Porto, Portugal. fatimafaria10@yahoo.com.br.
Fátima
F
Faria
CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801, Vila Real, Portugal. ligiamariabento@gmail.com.
Lígia M
LM
Lourenço
CECAV, Centro de Ciência Animal e Veterinária, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5000-801, Vila Real, Portugal. apires@utad.pt.
Maria Dos Anjos
Mdos A
Pires
D000230:Adenocarcinoma / Q000378:metabolism / Q000662:veterinary*; D000818:Animals; D014408:Biomarkers, Tumor; D002371:Cat Diseases / Q000378:metabolism*; D002415:Cats; D049109:Cell Proliferation / Q000502:physiology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000662:veterinary*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D007150:Immunohistochemistry / Q000662:veterinary; D053554:Keratin-20 / Q000235:genetics / Q000378:metabolism*; D053552:Keratin-7 / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D053554:Keratin-20; D053552:Keratin-7; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone