Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?

Abstract

BackgroundThis study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options.ResultsTwenty mammary tumor samples and their lymph node metastases were selected and stained by immunohistochemistry with anti-estrogen receptor (ER), -progesterone receptor (PR), -human epidermal growth factor receptor 2 (c-erbB-2), -cytokeratin 5/6 (CK 5/6), -cytokeratin 14 (CK14), -cytokeratin 19 (CK 19) and -protein 63 (p63) antibodies. Four phenotypes (luminal A, luminal B, c-erbB2 overexpressing and basal-like) were diagnosed in primary tumors and five (luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like) in the lymph node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%), and seven cases (35%) showed discordance with different lymph node phenotypic profile from the primary tumor.ConclusionsThe phenotype of the primary tumor assumes a predictive-therapeutic role only in concordant cases, meaning that both the primary tumor and its lymph node metastasis should be evaluated at the same time. A treatment plan based only on the primary tumor phenotype could lead to therapeutic failures if the phenotype of the lymph node metastasis differs from that of the primary tumor.

Significance of ERα, HER2, and CAV1 expression and molecular subtype classification to canine mammary gland tumor

“…28,31 The status for ERαN staining was used as described in the HBC 5-subtype classification. 4,8,13,28,29,32 For the HER2 and CAV1 IHC, after the sections were deparaffinized and rehydrated in xylene and in descending concentrations of ethanol as described above, HER2 and CAV1 antigens were retrieved with antigen retrieval solu- Description of the immunohistochemical evaluation for the target HER2. The Food and Drug Administration-approved scoring system for HBC, which is utilized in the HER2 expression Hercep test, q was used to evaluate overexpression of HER2.…”

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

“…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…”

Validation of Tissue Microarray for Molecular Profiling of Canine and Feline Mammary Tumours

“…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).…”

“…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.…”

“…Recently, in veterinary pathology this model of classification has been proposed and adapted for canine and feline primary mammary tumours and their lymph nodal and distant metastases (Beha et al, 2012(Beha et al, , 2014Brunetti et al, 2013).…”