G. Beha

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

The molecular characterization of mammary tumours represents a new stage in the development of effective predictive models and targeted therapies. The aim of this study was to evaluate the relationship between the molecular phenotype of a primary feline mammary tumour and that of a related lymph node metastasis. Twenty-one mammary tumour samples and their lymph node metastases were selected and evaluated immunohistochemically for expression of oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (c-erbB-2), cytokeratin 5/6, cytokeratin 14, cytokeratin 19 and protein 63. Mammary tumours were classified into five subtypes: luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like, based on an algorithm applied in both human and veterinary medicine. Concordance between the primary tumour and its lymph node metastasis was detected in 12 of 21 cases (57.1%). In the remaining nine cases (42.9%) there was discordance in the molecular profile at the two sites. Therefore, the tumour molecular profile must be evaluated in both sites in order to obtain definitive identification of the tumour profile (or profiles) and to plan an appropriate therapy.

Morphology of the myoepithelial cell: immunohistochemical characterization from resting to motile phase.

Myoepithelium is present in canine mammary tumors as resting and proliferative suprabasal and spindle and stellate interstitial cells. The aim of this paper was to evaluate a panel of markers for the identification of four different myoepithelial cell morphological types in the normal and neoplastic mammary gland and to investigate immunohistochemical changes from an epithelial to a mesenchymal phenotype. Cytokeratin 19 (CK19), cytokeratin 5/6 (CK5/6), cytokeratin 14 (CK14), estrogen receptor (ER), p63 protein, vimentin (VIM), and α-smooth muscle actin (Alpha-SMA) antibodies were used on 29 neoplasms (3 benign and 3 malignant myoepithelial tumors, 7 carcinomas in benign-mixed tumors and 16 complex carcinomas) and on normal tissue of mammary glands. All these antibodies were also tested on 3 mammary tissues from animals with no mammary pathology. The myoepithelial markers were well expressed in the suprabasal cells and gradually lost in the motile types, with the stellate cells maintaining only VIM expression typical of mesenchyma. ER labeled some resting and motile myoepithelial cells. On the basis of our results, we propose a transition from myoepithelial immotile cells into migratory fibroblast-like cells. This transition and the characterization of an immunohistochemical panel for resting and motile myoepithelial cells shed more light on the biological behavior of myoepithelial cells.

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

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.

Molecular Phenotype of Primary Mammary Tumours and Distant Metastases in Female Dogs and Cats

Distant metastases represent a major step in the progression and fatal outcome of canine and feline mammary carcinomas. Recent studies have characterized the molecular phenotypes of mammary tumours and provided information on molecules that may allow targeted therapy in sites from which the tumours may not readily be surgically resected. Molecular phenotypes were determined immunohistochemically in three feline and two canine cases of mammary neoplasia, each presenting with multiple distant metastases. These tumours and their metastases often overexpressed the c-erbB-2 phenotype. A basal-like phenotype was found in the distant metastases from two cases. These findings suggest that canine and feline mammary tumours with distant metastases may be amenable to novel targeted therapies.

CD117 Expression Influences Proliferation but not Survival in Canine Mammary Tumours

CD117 is a transmembrane tyrosine kinase receptor encoded by the c-Kit proto-oncogene. The immunohistochemical expression of CD117 was examined in 49 specimens of canine mammary glands (eight normal/hyperplastic, 11 benign tumours and 30 malignant tumours). Expression was assessed as: (1) presence or absence of CD117; (2) membrane, cytoplasmic, or both, distributions; and (3) percentage of CD117-labelled cells. None of these three immunohistochemical parameters was correlated with the type of mammary tissue (i.e. normal, benign or malignant), histotypes or histological stage of malignant tumours, or survival. An association was observed between Ki67 index and all three CD117 labelling parameters only for malignant tumours, with a significant increase in proliferative activity in tumours expressing CD117, mainly with both cytoplasmic and membrane expression.

Tyrosine Kinase Receptor Expression in Canine Liposarcoma

The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor–β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical labeling was categorized as high or low expression and compared with the mitotic count and MIB-1–based proliferation index. Fifty canine LPs were examined, classified, and graded. Fourteen cases were classified as well differentiated, 7 as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1, PDGFB, and PDGFRβ was identified in 62% (31/50), 68% (34/50), 81.6% (40/49), and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48) of the cases. Mitotic count negatively correlated with FGF2 (R = –0.41; P < .01), being lower in cases with high FGF2 expression, and positively correlated with PDGFRβ (R = 0.33; P < .01), being higher in cases with high PDGFRβ expression. No other statistically significant correlations were identified. These results suggest that the PDGFRβ-mediated pathway may have a role in the progression of canine LP and may thus represent a promising target for adjuvant cancer therapies.