Molecular Phenotype in Mammary Tumours of Queens: Correlation between Primary Tumour and Lymph Node Metastasis

Brunetti, Barbara; Asproni, Pietro; Beha, Germana; Muscatello, Luisa Vera; Millanta, Francesca; Poli, Alessandro; Benazzi, Cinzia; Sarli, Giuseppe

doi:10.1016/j.jcpa.2012.05.012

Cited by 31 publications

(41 citation statements)

References 22 publications

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“…3,38 For PR immunodetection, antigen retrieval was achieved with the same sodium citrate buffer in a water bath for 60 minutes at 95 C. For CK 5/6, samples were microwaved at 900 W for 15 minutes in Tris-EDTA buffer (pH 9.0). 2 Immunohistochemical analysis was performed with the primary antibodies summarized in Supplemental Table 1, and staining was achieved with a modified streptavidin-peroxidase conjugate method (Novolink MaxPolymer Detection System, Leica Biosystems, Wetzlar, Germany). Finally, tissue sections were counterstained with Mayer's hematoxylin (Merck, NJ, USA).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

et al. 2015

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Ki-67 is a nuclear protein and a proliferation marker frequently used in establishing the prognosis for breast cancer patients. To investigate the prognostic value of the Ki-67 proliferation index in female cats with mammary carcinoma, a prospective study was conducted with 96 animals. The Ki-67 index of primary tumors (n ¼ 96) was initially determined, and whenever possible, the Ki-67 index of regional lymph node metastasis (n ¼ 38) and distant metastasis (n ¼ 16) was also estimated. The optimal cutoff value for the Ki-67 index was determined by univariate and multivariate analysis. Ki-67 indices 14% were detected in 72.9% (70 of 96) of the tumors. Tumors with a Ki-67 index 14% were significantly associated with large size (P ¼ .022), poor differentiation (P ¼ .009), presence of necrotic areas (P ¼ .008), estrogen receptor-negative status (P < .0001), fHER2-negative status (P ¼ .003), and shorter overall survival (P ¼ .012). Moreover, Ki-67 expression in the primary tumor was strongly and positively correlated with both regional metastasis (P < .0001; r ¼ 0.83) and distant metastasis (P < .0001; r ¼ 0.83), and was significantly higher in distant metastases when compared with the primary tumor (P ¼ .0009). A similar correlation was also observed between regional and distant metastasis (P < .0001; r ¼ 0.75). On the basis of the above results, the authors propose the adoption of the 14% value as the optimal cutoff for Ki-67 to identify tumors with high risk of disease progression.Keywords feline mammary carcinoma, Ki-67 proliferation index, prognostic factor, cutoff value Feline mammary carcinomas (FMCs) are among the most prevalent tumors in cats, with an incidence that can reach 40% of all tumor cases in this species. 23,39,42 Contrary to those of humans and dogs, 85% to 93% of feline mammary tumors are considered malignant, and the most common histotypes are the tubular, papillary, solid, and cribriform carcinomas. 39 Feline mammary tumors may metastasize to the regional lymph nodes, lungs, and liver, as well as other organs. Although some studies correlate age, tumor size, presence of regional metastasis, and malignancy grade with overall survival (OS), 19,37,43 still scarce information is available regarding the proliferation index of FMC. Based on this scenario, additional prognostic and predictive factors may provide useful insights into tumor biology to achieve a more efficient therapy and a better follow-up of the affected female cats.Ki-67 is a protein found only in growing, dividing cells. It is expressed in all cell cycle phases, except in the resting phase (G0). With an intranuclear localization, the expression levels of Ki-67 are low during the G1 and S phases, rapidly increase during the G2 phase, and reach a peak in mitosis. This well-defined expression pattern makes the Ki-67 antigen a good proliferation marker, very useful and reliable in the prognosis of human breast cancer. 9,45 Several studies of women demonstrated that high Ki-67 expression is a poor prognostic indicator of 5-year rec...

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Section: Immunohistochemistrymentioning

confidence: 99%

Ki-67 as a Prognostic Factor in Feline Mammary Carcinoma

et al. 2015

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“…In veterinary medicine, there are only 2 studies comparing immunohistochemical phenotypes between primary mammary carcinomas and their related lymph node metastasis 12, 13. In cats, concordance between primary mammary carcinoma and matched metastasis was detected in 57.1% of cases,12 whereas in dogs in 65% of cases 13…”

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confidence: 99%

Concordance of c‐kit Mutational Status in Matched Primary and Metastatic Cutaneous Canine Mast Cell Tumors at Baseline

Marconato

Zorzan

Giantin

et al. 2013

Veterinary Internal Medicne

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BackgroundMutation analysis of proto‐oncogene c‐kit (c‐kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c‐kit mutation status does not change in metastasis.Hypothesis/ObjectivesTo give an insight into the mutational processes and to make a recommendation on the use of c‐kit mutational analysis in the clinical setting.AnimalsTwenty‐one client‐owned dogs with metastatic MCT.MethodsDogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.ResultsConcordance (mutated or wild‐type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c‐kit mutations were identified. No significant correlation was detected between c‐kit mutation and clinicopathologic features.Conclusions and Clinical ImportanceProto‐oncogene c‐kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c‐kit mutational testing. Targeted therapies might be also used to treat metastatic disease.

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“…Based on the algorithm (Beha et al, 2012;Brunetti et al, 2013), molecular phenotypes comprised three luminal B tumours, five c-erbB2 overexpressing tumours and one basal-like tumour, both in TMA and in FS. Only one case (number 8) had a discordant phenotype, namely luminal A in TMA and luminal B in FS (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…negative for OR, PR and c-erbB2). Application of the panel of immunohistochemical labels allowed the cases to be grouped into five molecular subtypes according to the algorithm described in the veterinary literature (Beha et al, 2012;Brunetti et al, 2013). Luminal A was defined as OR + and/or PR + , c-erbB-2 À , regardless of CK5/ 6, CK14 and p63 labelling; luminal B was defined as OR + and/or PR + , c-erbB-2 + , regardless of CK5/6, CK14 and p63 labelling; c-erbB-2 overexpressing tumours were defined as OR À , PR À , c-erbB-2 + , regardless of CK5/6, CK14 and p63 labelling; basal-like tumours were defined as OR À , PR À , c-erbB-2 À , CK5/6 + and/or CK14 + and/or p63 labelling; and null-type tumours were defined by no labelling with any marker.…”

Section: Methodsmentioning

confidence: 99%