Feline mammary Flashcards
Maniscalco et al. 2012. Activation of AKT in feline mammary carcinoma: a new prognostic factor for feline mammary tumors
Prognostic value of PI3K/AKT/PTEN pathway dysregulation in feline mammary tumors
p-AKT expression significantly correlated with?
Tumors expressing p-AKT had ____ disease free period than those with negative tumors
AKT activation was associated with ___ and ____
No AKT activation was observed in relation to ___
Tumor malignancy, histological differentiation, and clinical recurrence
Shorter
HER-2 expression and PTEN downregulation
ER or PR
Baptista et al. 2012. Sequence variation and mRNA expression of the TWIST1 gene in cats with mammary hyperplasia
Humans have germline mutation in TWIST1 oncogene may predispose to breast cancer and expression has been correlated with tumor progression and metastasis
Feline mammary CA had ___ of expression of TWIST1 mRNA than benign mammary tumors
Variations in TWIST1 coding region in feline mammary tumors
Lower levels
None, and no mutationa as people have
Penafiel-Verdu et al. 2012. Reduced expression of E-cadherin and B-catenin and high expression of basal cytokeratins in feline mammary carcinomas with regional metastasis
21 adenomas and 139 mammary carcinomas
66 of the carcinomas had metastasized, while 73 had regional LN mets at diagnosis
Preservation of E-cadherin and B-catenin is a significant feature of carcinomas without metastasis, wheras metastasis reveal the loss of one or both adhesion molecules
Basal cytokeratin was statistically associated with presence of regional metastasis
Expression of E-cadherin-B-catenin was correlated with high expression of CK18 and low expression of CK5/6
Ferrari et al. 2012. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis
Malignant feline mammary tumors express CXCR4 with higher level in malignant tumors and metastatic cells have stronger reactivity for CXCR4 than primary tumors
CXCR4 activation in primary cultures of feline mammary carcinoma causes increase in proliferation rate
SDF-1/CXCR4 system seems to play a tumorigneic role in feline mammary gland malignancy
Cherrington et al. 2012. Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline, human mammary tumors
PAD converts arginine residues in proteins to citrulline
Canine mammary gland, PAD2 is detected in epithelial cells in estrus and becomes widely expresses in diestrus
PAD2 appears to modify nuclear histone, suggesting a role for the enzyme in chromatin remodelling and gene regulation
Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but reduced expression in mammary carcinomas from both species
Feline mammary Ca had complete loss of nuclear PAD2 expression
Loss of PAD2 may represent marker of progression towards more aggressive neoplasia
Zappulli et al. 2012. Immunohistochemical expression of E-cadherin and B-catenin in feline mammary tumors
IHC expression of E-cadherin and B-catenin in 53 mammary tumors and 48 hyperplastic or dysplastic lesions from 57 queens
E-cadherin and B-catenin expression was membranous in all samples and significant decrease in malignant tumors and metastases
Cytoplasmic expression of both markers was inversely correlated to membrane localization
B-catenin nuclear labeling detected in 1 LN (60% positive cells) and in basal/myoepithelial cells of 6/7 ductal tumors
No correlation with survival was found with either marker
Pang et al. 2013. Feline mammary carcinoma stem cells are tumorigenic, radioresistant, chemoresistant, and defective in activation of ATM/p53 DNA damage pathway
Feline mammary carcinoma stem cells were resisatnt to chemotherapy and radiation, possibly due to aberrant activation of the ATM/p53 DNA damage pathway.
EMT was feature of invasive phenotype
Results demonstrate CSC are a feature of mammary cancer in cats
Maniscalco et al. Activation of mTOR in triple negative feline mammary carcinomas
Triple negative breast cancer (TNBC) - absent ER, PR, and HER2 overexpression. mTOR is overexpressed in TNBC and represents a target
Study investigated mTOR and p-mTOR expression in FMC in relation to TN phenotype
53.3% of FMC were ER, PR, HER2 negative while 56.9% and 55.2% expressed mTOR and p-mTOR
Wiesse et al. 2013. Feline mammary basal-like ACAs: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype
TNBC - negative for ER, PR, HER2
Subpopulation of TNBC have basal like morphology - positive for CK5/6 and/or EGFR and high incidence of BRCA mutations
24 FMAs were classified
14 of 24 (58%) FMA were triple negative, 11/14 (79%) had basal like subtype with no genetic abnormality in BRAC1 or BRAC2
Michishita et al. 2013. Flow cytometric analysis for detection of tumor-initiating cells in feline mammary carcinoma cell lines
(TICs) - have the capacity to self-renew, differentiate, and form tumors at high frequency, has a potential role in tumor initiation, aggression, and recurrence.
In human breast cancers, TICs are identified by surface markers, such as CD44 and CD24, and an aldefluor assay based on aldehyde dehydrogenase activity (ALDH(+)) using flow cytometry.
We attempted to identify CD44(+)CD24(-) and ALDH(+) cells using 8 feline mammary carcinoma cell lines, including FKNp, which was obtained from a primary lesion, and the capacity to generate tumor nodules was analyzed in immunodeficient mice injected with ALDH(+) FKNp-derived cells.
The CD44(+)CD24(-) and ALDH(+) cells were detected in all cell lines derived from feline mammary carcinomas. Xenograft transplantation into immunodeficient mice demonstrated that as few as 1 × 10(2) ALDH(+) cells could initiate tumor growth in 1 out of 4 mice, while 1 × 10(3) ALDH(+) cells initiated tumor growth in 5 out of 6 mice. However, 1 × 10(3) ALDH(-) cells failed to initiate tumors in all the tested mice. ALDH(+)-derived tumors contained both ALDH(+) and ALDH(-) cells, indicating that ALDH(+) FKNp-derived cells had higher tumorigenicity than ALDH(-) cells.
These results suggest that TICs may exist in feline mammary carcinomas, and further characterization of CD44(+)CD24(-) and ALDH(+) cells is needed to define novel therapies targeted against TICs. This study provides the foundation for elucidating the contribution of TICs in tumorigenesis.
Buendia et al. 2013. N-cadherin expression in feline mammary tumors is associated with reduced E-cadherin expression and the presebce if regional metastasis
N-cadherin is expressed by neural and fibroblast cells but not epithelial cells
Some studies in human suggest switch from N-cad to E-cad as a step in malignant progression
21 adenomas and 139 carcinomas
Results showed statistically significant relation between expression of N-cad and 2 prognostic factors and also reduced expression of E-cad in tumors that expressed N-cad
Flores et al. 2014. Reduced ezpression of claudin-2 is associated with high histological grade and metastasis of feline mammary carcinomas
Claudins are family of tight junction proteins and play role in cell polarity, controlling paracellular ion flux and regulating proliferation and differentiation
Evidence suggets changes in caludin expression and development of human breast cancer
CLDN expression in normal feline mammary tissue (5), mammary carcinomas (52), metastatic lesions (29)
77% of carcinomas had reduced CLDN expression compared to normal mammary gland
Reduced expression of CLDN-2 was significantly associated with high histologic grade of carcinoma, with 88.6% of grade II/III carcinomas showing decreased expression
CLDN-2 downregulation was associated with metastatic disease, with 93% have decreased protein expression
Santos et al. 2013. ERB2 in cat mammary neoplasias disclosed a positive correlation between RNA an dprotein low expression levels: a model for erbB2 negative human breast cancer
Millanta et al. 2016. COX-2, mPGES-1 and EP2 receptor immunohistochemical expression in canine and feline malignant tumors
PGE2 is controlled by COX-2 and microsomal PGE synthase-1 (mPGES-1). PG singlaing is involved in human and animal cancer development
COX-2 positivity occured in 83% canine and 81% feline mammary tumors
mPGES-1 in 75% of canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas
Frequency of COX-2, EP2 receptor and mPGES-1 expression was significantly higher in carcinomas than non-neoplastic tisssues and adenomas
Mills et al. 2015. Prognostic value of histologic grading for feline mammary carcinoma: a retrospective survival analysis
Evaluate the Elston and Ellis grading system (originally developed for human breast cancer) for feline mammary carcinoma
Elston and Ellis grading failed to correlate with overall survival
Using multivariable analysis, lymphovascular invasion, nuclear form, and mitotic counr each demonstrated independentd prognostic significance
Modification of the Elston and Ellis grading system - correlation with overall survival
MST 27, 29, 31 months for grade 1, 14, 12, or 14 months for grade 2, 13, 5, 8 for grade 3 using modified Ellis system
Adelfinger et al. 2014. Evaluation of a new recombinant oncolytic vaccinia virus strain GLV-5b451 for feline mammary carcinoma therapy
Flores et al. 2014. Clinicopathologic significance of immunoexpression of caludin-1 and claudin-7 in feline mammary CAs
Inverse association between CLDN-7 and histological grade of tumor
Reduced expression of CLDN-7 was significantly associated with decreased tubule formation, high proliferative activity and metastasis
No significant association was found between CLDN-1 expression
Caliari et al. 2014. Triple-negative vimentin positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer
A large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation.
Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor.
Soares et al. 2016. Ki-67 as a Prognostic factor in feline mammary carcinoma: what is the optimal cutoff value?
Ki-67 indices of >14% were detected in 72.9% of the tumors.
Tumors with Ki-67 index>14% were signifcantly associated with large size, poor differentiation, and presence of necrotic areas, ER-negative status, fHER2-negative status, and shorter survival time
Ki-67 expression in primary tumor was strongly and positively correlated with both regional and distant metastasis
Cut-off value of 14% to identify high risk of disease progression
Beffagna et al. 2016. A preliminary investigation of the role of transcription co-activators YAP/TAZ of the Hippo signaling pathway in canine and feline mammary tumors
YAP/TAZ transcription co-activators of the Hippo pathway sustain self-renewal and tumor initiation of CSCs
Increased cytoplasmic and nuclear expression of YAP/TAZ was observed in all carcinomas compared to normal tissues
Nuclear expression significantly increased in grade III compared to grade I - YAP/TAZ play a role increased aggressiveness
Silva et al. 2017. Histologic evaluation of Ki-67 and cleaves caspace-3 expression in feline mammary carcinoma
Positive immunostaining was observed in all cancer samples for both nuclear Ki-67 and cleaved caspace-3 with mean positive staining percentage of 27.5% and 21.2%
No correlation between ki-67 and cleaved caspace-3 observe in feline mammary carcinoma
High proliferative index in FMC
Graf et al. 2016. Swiss feline cancer registry 1965-2008: the influence of sex, breed and age on tumor types and tumor locations
Largest breed difference was found in development of FSA and SCC and tumors in skin/subcutis and mammary gland
Tumors mor frequent in middle-ages to older cats
Gray et al. 2017. Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro
EGFR/ERBB are frequently disregulated in human cancers
EGFR and ERBB2 combines siRNA targeting produced synergistic effects in feline and canine cell lines similar to reported human cell lines
Dual EGFR and ERBB2 targeting urins TKIs should be evaluated
Hassan et al. 2017. Feline Mammary Cancer
