Expression of VCAN and its receptors in canine mammary carcinomas with or without myoepithelial proliferation.

The proteoglycan versican (VCAN) plays a complex role in cancer. The expression of this molecule has been related to invasion and progression in malignant mixed tumors, such as carcinoma in mixed tumors (CMT) of the canine mammary gland. In addition, its interaction with surface cell receptors EGFR, HER-2 and CD44 in malignant epithelial cells may be responsible for proliferation and cellular motility in early stages of cancer. We comparatively evaluated the expression of this proteoglycan and its receptors in in situ and invasive areas of simple carcinomas (SC) and CMT to investigate similarities and differences between these histological types. Immunohistochemistry was performed with anti-VCAN, anti-CD44, anti-EGFR and anti-HER-2 antibodies in 32 cases of SC or CMT. VCAN was highly expressed in stroma adjacent to invasive areas in SC and CMT. CMTs presented comparatively higher expression of VCAN in stroma adjacent to in situ and in invasive areas than in corresponding areas in SCs. In CMT, EGFR and HER-2 expressions were higher in situ compared to invasive areas. In contrast, increased CD44 and EGFR expression was found in invasive areas in SC compared to CMT. These results indicate that versican expression is similarly associated with invasiveness in SC and CMT, however higher levels were seen in CMT suggesting that the presence of myoepithelial proliferation in this tumor type participates in stromal composition and promoting an increase in the expression of versican.

Glycogen-rich clear cell carcinoma of the feline mammary gland: case report / Carcinoma de células claras rico em glicogênio da glândula mamária felina: relato de caso

The aim of this report is to describe the first histopathological, immunohistochemical, and clinical characteristics of a feline glycogen-rich clear cell carcinoma (GRCCC). A Persian queen was admitted with mammary gland tumors and underwent radical unilateral mastectomy. Overall survival was considered 33 days and death was due to clinical evolution of the disease. Microscopic evaluation demonstrated epithelial cells arranged in a predominantly solid pattern, tumor cells presented an ample, granular, and foamy clear cytoplasm, and moderate cellular pleomorfism. The presence of cytoplasmatic glycogen was confirmed through diastase digestion followed by PAS staining. Histopathological and histochemical findings lead to the diagnosis of GRCCC with regional metastases.(AU)

O objetivo deste relato de caso é descrever as características clínicas, histopatológicas e imuno-histoquímicas do primeiro carcinoma mamário de células claras rico em glicogênio em felino. Uma gata persa foi atendida com tumores na glândula mamária e foi submetida à mastectomia radical unilateral. A sobrevida livre de doença foi considerada 33 dias, e o óbito foi devido à evolução da doença. A avaliação microscópica demonstrou células epiteliais arranjadas em um padrão predominantemente sólido, as células tumorais apresentaram um citoplasma claro, amplo, granular e espumoso e pleomorfismo celular moderado. A presença do glicogênio citoplasmático foi confirmada pela digestão pela diástase, seguida da coloração de PAS. Achados histopatológicos e histoquímicos levaram ao diagnóstico de carcinoma de células claras rico em glicogênio felino com metástase regional.(AU)

HER-2, EGFR, Cox-2 and Ki67 expression in lymph node metastasis of canine mammary carcinomas: Association with clinical-pathological parameters and overall survival.

Studies about canine mammary tumors based on single molecular markers probably cannot accurately account for the heterogeneity of this disease, and the investigation of multiple molecular alterations in primary tumors and their metastases, in conjunction, has assumed great importance for the understanding of mammary tumor progression. In the present study, we selected 54 primary mammary carcinomas with lymph node metastasis (T1,2,3N1M0), 29 primary mammary carcinomas without metastasis (T1,2,3N0M0), and 25 canine lymph nodes metastasis to evaluate the immunohistochemical expression of HER-2, EGFR, Cox-2 and Ki67 and its association with clinical-pathological parameters and overall survival. Our results found a concordance between the expression of HER-2 (K coefficient: 0.250), Cox-2 (K coefficient: 0.571), and Ki67 (K coefficient: 0.397) and a discordance between EGFR expression (K coefficient: -0.195) in primary mammary carcinomas and paired lymph node metastasis. Furthermore, a high Ki67 index (>24%), large tumor size and the presence of angiolymphatic invasion in canine primary mammary carcinoma with lymph node metastasis plus the presence of extracapsular extension in lymph nodes metastasis were also related to worse prognoses and shorter overall survival (P<0.05). In conclusion, our study demonstrates that primary mammary carcinomas with high expression of HER-2, Cox-2 and Ki67 also show high expression of these markers in paired lymph node metastasis. Moreover, the expression of these molecular markers in lymph nodes metastasis did not demonstrate a prognostic relevance.

Plasma biomarkers profile of female dogs with mammary carcinoma and its association with clinical and pathological features.

The immunological biomarkers profiles were evaluated using Luminex as putative measures to monitor canine mammary carcinomas (MCs). Forty female dogs were categorized into benign mixed tumour (MC-BMT = 28) and mammary carcinoma (MC=12). The ascendant biomarker signatures were used to compare the groups. For example, a higher frequency of MC-BMT animals producing IL-6, CXCL-8 and CXCL-10 was observed, whereas for the MC group IL-2 and CXCL-8 were detected. MC-BMT animals without metastasis had an increase in the levels of IL-2, CXCL-8, CXCL-10, IL-6, TNF-α, IL-15 and a decrease in IL-10 and CXCL-8. MC-BMT animals with metastasis showed only an increase in CXCL-10 and a decrease in IL-18. After comparing the ascendant signatures following the presence of metastasis in both groups, a higher frequency of dogs exhibiting IL-10 production was observed. Pearson correlation (P = 0.0273) and receiver operating characteristic (ROC) curve analysis revealed that this pattern was associated with worse outcome and lower survival rates in MC animals.

Relationship between the expression of versican and EGFR, HER-2, HER-3 and CD44 in matrix-producing tumours in the canine mammary gland.

Versican is an extracellular matrix proteoglycan that has been identified as a modulator of adhesion loss, cell motility, and tumour progression. This motility results from the interaction between versican and cell surface receptors. Studies have also demonstrated the relationship between this molecule and invasion in canine mammary tumours. Given the evidence for the participation of proteoglycans in tumour progression, this study aimed to assess versican expression and its association with cell surface receptors; human epidermal growth factor receptors 1, 2, and 3 (EGFR, HER-2, and HER-3) and CD44 through an immunohistochemical analysis of benign mixed tumours (BMTs), carcinomas in mixed tumours (CMTs), and carcinosarcomas (CSs) of the canine mammary gland. Malignant tumours were divided into low and high groups with respect to versican stromal expression. The results indicated that the BMTs showed weak stromal versican expression and correlations between the expression of stromal versican and EGFR in the epithelial membrane in benign areas (p=0.013, r=0.571). A higher stromal versican expression was observed adjacent to invasive epithelial areas compared with in situ areas in CMTs and CSs, suggesting a direct relationship between versican expression and invasiveness. Furthermore, the CSs exhibited a higher expression of HER-2, cytoplasmic HER-3, and CD44 in epithelial invasive cells in cases of higher stromal versican expression. Therefore, the cell surface receptors (HER-2, HER-3, and CD44) are more evident in CSs that overexpress versican in stroma adjacent to the invasive areas. These findings suggest that the association between these molecules may be directly related to the biological behaviour and invasiveness of these canine mammary tumours.

Tubulopapillary carcinoma of the mammary gland in a maned wolf (Chrysocyon brachyurus): histopathological and immunophenotypical analysis / Carcinoma túbulo-papilar da glândula mamária em lobo guará fêmea (Chrysocyon brachyurus): análise histopatológica e imunofenotípica

A maned female wolf (Chrysocyon brachyurus) showed nodules in the inguinal and left abdominal cranial mammary glands. The mammary gland was surgically excised, and microscopic analysis revealed epithelial cell proliferation in a tubular and papillary pattern; delicate fibrovascular stalks presenting numerous layers of moderately pleomorfic epithelial cells were observed. This histologic appearance was compatible with a diagnosis of mammary tubulopapillary carcinoma. The immunohistochemical profile revealed nuclear positivity for estrogen (70 percent) and progesterone (at least 90 percent of the neoplastic cells). The myoepithelium-associated with neoplastic cells lacked integrity, as evidenced by failed smooth muscle alpha actin reactivity in microinvasive areas. A low proliferation index was observed (3.4 percent). To the authors' knowledge, the present case represents the first finding of female tubulopapillary carcinoma in a mammary gland in this species.

Um lobo guará fêmea (Chrysocyon brachyurus) apresentou nódulos nas mamas inguinal e abdominal cranial esquerda. As glândulas mamárias foram cirurgicamente excisadas, e na análise microscópica revelaram proliferação de células epiteliais em arranjo tubular e papilar com tecido conjuntivo de sustentação delicado e formação múltiplas camadas de células epiteliais moderadamente pleomórficas. Os achados histopatológicos foram compatíveis com carcinoma túbulo-papilar da glândula mamária. O estudo do perfil imuno-histoquímico mostrou positividade nuclear para estrógeno (70 por cento) e progesterona (em pelo menos 90 por cento das células). Observou-se perda da integridade da camada mioepitelial, adjacente a proliferação epitelial, evidenciada pela perda de reatividade para alfa actina de músculo liso em áreas de microinvasão. Índice de proliferação celular baixo foi observado (3,4 por cento). O presente relato representa a primeira descrição de um carcinoma túbulo-papilar da glândula mamária em uma fêmea desta espécie.

Cistoadenocarcinoma simulando hemangiossarcoma de glândula salivar em cão: relato de caso / Cystadenocarcinoma simulating hemangiosarcoma of the salivary gland in dog: case report

Cystadenocarcinoma is regarded as a rare adenocarcinoma variant in animals. This work reports the case of an 8-year-old female Poodle dog with salivary gland cystadenocarcinoma with morphological characteristics similar to a hemangiosarcoma. Histopathological analysis showed a tumor mass with cystic formations containing a large amount of red blood cells. In order to distinguish these two entities, periodic acid Schiff (PAS) staining and immunohistochemical analysis were carried out with the use of cytokeratin AE1/AE3 (CK) and CD31-specific antibodies. Neoplastic cells were PAS-negative, CK-positive and CD31-negative confirming their epithelial origin. Based on the findings, the diagnosis of high grade cystadenocarcinoma was established.

O cistoadenocarcinoma é considerado uma variante do adenocarcinoma de rara ocorrência em animais. Este trabalho relata um caso de cadela Poodle de oito anos, portadora de cistoadenocarcinoma de glândula salivar com características morfológicas semelhantes a de hemangiossarcoma. Na análise histopatológica observou-se uma massa tumoral com formações císticas contendo grande quantidade de hemácias. Para a diferenciação entre as duas entidades realizou-se coloração pelo ácido periódico de Schiff (PAS) e análise imuno-histoquímica com a utilização de anticorpos para citoqueratina AE1/AE3 (CK) e CD31. As células neoplásicas apresentaram-se PAS negativas, CK positivas e CD31 negativas demonstrando a origem epitelial. Com base nos achados firmou-se o diagnóstico de cistoadenocarcinoma de alto grau.