ZEB2 and ZEB1 expression in a spontaneous canine model of invasive micropapillary carcinoma of the mammary gland

Abstract Background: Invasive micropapillary carcinoma (IMPC) is a rare malignant breast tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the human breast and canine mammary gland. The importance of the tumor microenvironment in cancer development has gradually been recognized, but little is known about the cell types outlining the cystic space of canine IMPC. This study aimed to characterize the neoplastic cells outlining the cystic space of IMPC.Methods: Immunohistochemistry (IHC), immunofluorescence (IF), superresolution and transmission electron microscopy (TEM) were used to assess the cell types in the cystic areas of IMPCs.Results: Cells expressing the mesenchymal markers alpha-smooth muscle actin (aSMA), Vimentin, and S100A4 outlined the cystic space of IMPC. Furthermore, loss of epithelial cell polarity in IMPC was shown by the localization of MUC1 at the stroma-facing surface. This protein modulates lumen formation and inhibits the cell-stroma interaction. Immunohistochemical and IF staining for the myoepithelial cell marker p63 were negative in IMPC samples, and TEM revealed morphological aspects of myoepithelial-like cells with thin cytoplasmic extensions outlining the cystic space.Conclusions: The cells outlining the cystic space of IMPC in the canine mammary gland were characterized using IHC, IF and TEM. The presence of cells expressing aSMA, Vimentin, and S100A4 in the IMPC stroma suggested a role for tumor-associated fibroblasts in the IMPC microenvironment. The reversal of cell polarity revealed by the limited basal localization of MUC1 may be an important factor contributing to the invasiveness of IMPC. For the first time, the cystic space of canine mammary gland IMPC was shown to be delimited by myoepithelial-like cells that had lost p63 expression. These findings may enhance our understanding of the cellular microenvironment of invasive tumors to improve cancer diagnosis and treatment.

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The diagnostic importance of invasive micropapillary carcinoma in the canine mammary gland: clinicopathological, immunohistochemical and survival analysis

BMC Proceedings ◽

10.1186/1753-6561-7-s2-p17 ◽

2013 ◽

Vol 7 (Suppl 2) ◽

pp. P17

Author(s):

Conrado O Gamba ◽

Éverton J Dias ◽

Lorena GR Ribeiro ◽

Liliane C Campos ◽

Alessandra Estrela-Lima ◽

...

Keyword(s):

Survival Analysis ◽

Mammary Gland ◽

Invasive Micropapillary Carcinoma ◽

Micropapillary Carcinoma ◽

Canine Mammary Gland ◽

Diagnostic Importance

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Characterization of neoplastic cells outlining the cystic space of invasive micropapillary carcinoma of the canine mammary gland

BMC Veterinary Research ◽

10.1186/s12917-021-02807-y ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Michele A. Rodrigues ◽

Andre L. Caldeira-Brant ◽

Dawidson A. Gomes ◽

Tatiany L. Silveira ◽

Hélio Chiarini-Garcia ◽

...

Keyword(s):

Mammary Gland ◽

Cell Polarity ◽

Ductal Carcinoma ◽

Cell Types ◽

Variant Form ◽

Invasive Micropapillary Carcinoma ◽

Micropapillary Carcinoma ◽

Neoplastic Cells ◽

Cystic Space ◽

Canine Mammary Gland

Abstract Background Invasive micropapillary carcinoma (IMPC) is a rare malignant breast tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the human breast and canine mammary gland. The importance of the tumor microenvironment in cancer development has gradually been recognized, but little is known about the cell types outlining the cystic space of canine IMPC. This study aimed to characterize the neoplastic cells outlining the cystic space of IMPC. Results Immunohistochemistry (IHC), immunofluorescence (IF), superresolution and transmission electron microscopy (TEM) were used to assess the cell types in the cystic areas of IMPCs. Cells expressing the mesenchymal markers alpha-smooth muscle actin (αSMA), Vimentin, and S100A4 outlined the cystic space of IMPC. Furthermore, loss of epithelial cell polarity in IMPC was shown by the localization of MUC1 at the stroma-facing surface. This protein modulates lumen formation and inhibits the cell-stroma interaction. Immunohistochemical and IF staining for the myoepithelial cell marker p63 were negative in IMPC samples. Furthermore, associated with peculiar morphology, such as thin cytoplasmic extensions outlining cystic spaces, was observed under TEM. These observations suggested cells with characteristics of myoepithelial-like cells. Conclusions The cells outlining the cystic space of IMPC in the canine mammary gland were characterized using IHC, IF and TEM. The presence of cells expressing αSMA, Vimentin, and S100A4 in the IMPC stroma suggested a role for tumor-associated fibroblasts in the IMPC microenvironment. The reversal of cell polarity revealed by the limited basal localization of MUC1 may be an important factor contributing to the invasiveness of IMPC. For the first time, the cystic space of canine mammary gland IMPC was shown to be delimited by myoepithelial-like cells that had lost p63 expression. These findings may enhance our understanding of the cellular microenvironment of invasive tumors to improve cancer diagnosis and treatment.

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Invasive micropapillary carcinoma of the dog mammary gland: a case report

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352002000400006 ◽

2002 ◽

Vol 54 (4) ◽

pp. 366-369 ◽

Cited By ~ 16

Author(s):

G.D. Cassali ◽

R. Serakides ◽

F. Gärtner ◽

F.C. Schmitt

Keyword(s):

Mammary Gland ◽

Case Report ◽

Epithelial Cells ◽

Breast Tumor ◽

Morphological Features ◽

Invasive Micropapillary Carcinoma ◽

Micropapillary Carcinoma ◽

Micropapillary Pattern

This report describes the morphological and immunohistochemical findings of two cases of breast invasive micropapillary carcinoma occurring in dogs. Histologically, the tumors are characterized by the presence of numerous irregular cystic formations filled out with nests of epithelial cells that exhibit a micropapillary pattern. These morphological features are characteristic of invasive micropapillary carcinoma in woman, a breast tumor not previously described in dogs.

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Correction: The investigation of transcriptional repression mediated by ZEB2 in canine invasive micropapillary carcinoma in mammary gland

PLoS ONE ◽

10.1371/journal.pone.0214567 ◽

2019 ◽

Vol 14 (3) ◽

pp. e0214567

Author(s):

Conrado de Oliveira Gamba ◽

Karine Araújo Damasceno ◽

Izabel Cristina Ferreira ◽

Michele Angela Rodrigues ◽

Dawidson Assis Gomes ◽

...

Keyword(s):

Mammary Gland ◽

Transcriptional Repression ◽

Invasive Micropapillary Carcinoma ◽

Micropapillary Carcinoma

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Characterization of Neoplastic Cells in the Cystic Space of Invasive Micropapillary Carcinoma of the Canine Mammary Gland.

10.21203/rs.3.rs-46843/v1 ◽

2020 ◽

Author(s):

Michele Angela Rodrigues ◽

Andre L. Caldeira-Brant ◽

Dawidson Assis Gomes ◽

Tatiany L. Silveira ◽

Hélio Chiarini-Garcia ◽

...

Keyword(s):

Mammary Gland ◽

Stromal Cells ◽

Ductal Carcinoma ◽

Variant Form ◽

Invasive Micropapillary Carcinoma ◽

Micropapillary Carcinoma ◽

Cystic Space ◽

First Time ◽

Canine Mammary Gland

Abstract Background: Invasive micropapillary carcinoma (IMPC) is a rare breast malignant tumor and a variant form of invasive ductal carcinoma that is an aggressive neoplasm of the canine mammary gland and the human breast. There is a progressed recognition of the importance of the tumor microenvironment in cancer development, but little is known about cell types expressed in the cystic space of canine IMPC. This study aimed to investigate the neoplastic and stromal cells surrounding the cystic space in IMPC. Methods: It was used immunohistochemistry (IHC), immunofluorescence (IF), super-resolution microscope and transmission electron microscopy (TEM) to access the localization and morphology of both stromal cells and epithelial cells in canine IMPC cystic areas.Results: Cells surrounding the cystic space in IMPC were positive for the mesenchymal marker's alpha-smooth muscle actin (aSMA), Vimentin, and S100A4. Furthermore, myoepithelial cell marker p63 was negative on IMPC. Tumoral reversal polarity was observed using MUC1 for the first time in IMPC from the canine mammary gland. MUC1 is known to have a role in lumen formation and has an inhibitory role in the cell to stroma interaction. TEM showed that cells lining the IMPC cystic space were modified myoepithelial cells. Conclusion: The present work demonstrates, for the first time, a characterization of the cystic space compound on IMPC from the canine mammary gland. These findings could be useful to understand better the cellular microenvironment in invasive tumors of the mammary gland to improve cancer treatment.

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