Reduced Expression of E-cadherin and β-catenin and High Expression of Basal Cytokeratins in Feline Mammary Carcinomas With Regional Metastasis

Abstract

Feline mammary carcinomas are highly aggressive neoplasms. Several mechanisms are thought to be involved in their progression, including the loss of epithelial adhesion molecules. The present study was carried out on 21 adenomas and 139 mammary carcinomas. Of the carcinomas, 66 were not reported to have metastasized, while the remaining 73 had evidence of regional lymph node metastasis at the moment of diagnosis. The relationship was examined between the expression of the E-cadherin-b-catenin complex and basal (CK5/6, CK14) and luminal (CK8/18) cytokeratin expression. In the medical literature, carcinomas expressing basal cytokeratins are reported as having a poor prognosis in human breast cancer. Results revealed that preservation of the expression of E-cadherin and b-catenin is a significant feature of carcinomas without metastasis, whereas carcinomas with metastasis reveal the loss of one or both adhesion molecules. Additionally, basal cytokeratin expression was statistically associated with the presence of regional metastasis. Furthermore, the expression of E-cadherin-b-catenin was significantly correlated with the high expression of CK18 and low expression of CK5/6. Keywords feline mammary carcinoma, immunohistochemistry, E-cadherin, b-catenin, basal cytokeratinsMammary neoplasia is the third-most-common tumor type affecting female cats, following hemopoietic neoplasms and skin tumors. Malignancy is frequently reported and presents with local and distant metastases and high mortality rates. 42 Based on age, incidence, risk factors, histopathology, prognostic aspects, metastatic pattern, and response to therapy, feline mammary carcinomas have been proposed as a good model for human breast cancer. 2,42 Similar to reports in women, many veterinary studies describe regional lymph node involvement as one of the most important prognostic factors for feline mammary tumors. 11,16

Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer

“…Although there are no robust and standardized results for hormone receptors (HRs) and HER2 positivity, feline mammary carcinomas (FMCs) often lack significant levels of ERa and PR [17-23]. In addition, FMCs have been associated with decreased expression of adhesion molecules [24] and high expression of basal cytokeratins and vimentin [25], and a “basal-like” subtype was identified by IHC-analyses [17]. …”

N-cadherin Expression in Feline Mammary Tumors Is Associated With a Reduced E-cadherin Expression and the Presence of Regional Metastasis

“…5,6 The role of E-cadherin has also been studied recently in feline mammary carcinomas in which preservation of this protein was associated with maintaining tissue architecture and inhibiting tumor cell invasiveness. 11,14 However, no studies have been published in veterinary science about cadherin switching involving the loss of E-cadherin and the expression of N-cadherin in mammary carcinomas. The aim of the present study is to analyze the expression of N-cadherin using a series of feline mammary adenomas and carcinomas (with and without regional metastasis) whose World Health Organization (WHO) classification, grading, and immunohistochemical expression of E-cadherin had previously been published.…”

“…11 Tumors with regional micrometastases were classified as metastatic carcinomas. Carcinomas had been classified 11 according to the WHO as tubulopapillar (46/139), cribiform (62/139), or solid (31/139). The grading of the carcinomas had been obtained 11 by the modification of the Nottingham method described by Castagnaro et al 4 The grading revealed 37 grade I, 66 grade II, and 36 grade III carcinomas.…”

“…Carcinomas had been classified 11 according to the WHO as tubulopapillar (46/139), cribiform (62/139), or solid (31/139). The grading of the carcinomas had been obtained 11 by the modification of the Nottingham method described by Castagnaro et al 4 The grading revealed 37 grade I, 66 grade II, and 36 grade III carcinomas. The expression of E-cadherin had been analyzed in a previous study, 11 following the method described by Brunetti et al 3 As previously published, 11 all the adenomas (n ¼ 21) showed normal membrane labeling of Ecadherin, while only 72 of the 139 carcinomas exhibited this pattern of expression.…”

“…The grading of the carcinomas had been obtained 11 by the modification of the Nottingham method described by Castagnaro et al 4 The grading revealed 37 grade I, 66 grade II, and 36 grade III carcinomas. The expression of E-cadherin had been analyzed in a previous study, 11 following the method described by Brunetti et al 3 As previously published, 11 all the adenomas (n ¼ 21) showed normal membrane labeling of Ecadherin, while only 72 of the 139 carcinomas exhibited this pattern of expression. The other 67 carcinomas showed a reduced membrane expression of E-cadherin; in most cases, this reduced E-cadherin expression consisted of a combination of reduced labeling in the membrane and cytoplasmatic expression, and only 6 carcinomas showed exclusively cytoplasmic expression of the protein.…”