Cytokeratins as markers of initial stages of squamous metaplasia in feline mammary carcinomas

D. Ivanyi From the Division of Tumor Biology (Ivanyi, Minke, Hageman, Groeneveld, van Doornewaard), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam; and Department of Veterinary Pathology, Faculty of Veterinary Medicine, State University, Utrecht, The Netherlands (Misdorp).

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J. M. H. M. Minke From the Division of Tumor Biology (Ivanyi, Minke, Hageman, Groeneveld, van Doornewaard), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam; and Department of Veterinary Pathology, Faculty of Veterinary Medicine, State University, Utrecht, The Netherlands (Misdorp).

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Ph. C. Hageman From the Division of Tumor Biology (Ivanyi, Minke, Hageman, Groeneveld, van Doornewaard), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam; and Department of Veterinary Pathology, Faculty of Veterinary Medicine, State University, Utrecht, The Netherlands (Misdorp).

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E. Groeneveld From the Division of Tumor Biology (Ivanyi, Minke, Hageman, Groeneveld, van Doornewaard), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam; and Department of Veterinary Pathology, Faculty of Veterinary Medicine, State University, Utrecht, The Netherlands (Misdorp).

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G. van Doornewaard From the Division of Tumor Biology (Ivanyi, Minke, Hageman, Groeneveld, van Doornewaard), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam; and Department of Veterinary Pathology, Faculty of Veterinary Medicine, State University, Utrecht, The Netherlands (Misdorp).

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W. Misdorp From the Division of Tumor Biology (Ivanyi, Minke, Hageman, Groeneveld, van Doornewaard), The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam; and Department of Veterinary Pathology, Faculty of Veterinary Medicine, State University, Utrecht, The Netherlands (Misdorp).

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Summary

Expression of keratins (cytokeratins, ck) known to be suitable markers for different types of epithelial differentiation was analyzed in specimens of feline mammary tissue. A panel of specific anti-ck monoclonal antibodies (MAb) was used to determine ck distribution pattern in normal feline tissues (n = 3), and in benign (n = 18) and malignant (n = 20) feline mammary tumors. In selected tumors, the ck distribution pattern was also determined by biochemical methods. A MAb specific for α-smooth muscle actin was used to discriminate between myoepithelial cells and luminal epithelial cells.

In normal mammary gland tissues, 6 MAb reacted exclusively, either with myoepithelial cells or with luminal epithelial cells. Luminal epithelial cells reacted with MAb specific for ck typical of simple epithelia, whereas myoepithelial cells reacted with MAb specific for ck in basal cells of stratified epithelia. A similar distribution of ck was detected in specimens from benign tumors, except that ck4 was not detected in normal mammary gland tissues and was detected in some ducts in specimens with adenosis. Almost all tumor cells in specimens from malignant tumors reacted with MAb specific for ck typical of simple epithelia. Concomitant expression of ck typical of stratified epithelia was detected in small or large subpopulations of tumor cells in 70% of carcinomas. Cytokeratins typical of basal cell layers and typical for suprabasal layers of inner stratified epithelia were detected. Cytokeratins typical of stratified epithelia were always found in areas of squamous metaplasia, but also were found in adenocarcinomal cells surrounding these areas. We postulate that these adenocarcinoma cells represent transitional cells where the initial stages of squamous metaplasia have taken place, but squamous metaplasia is not yet detectable by light microscopy.

Summary

Expression of keratins (cytokeratins, ck) known to be suitable markers for different types of epithelial differentiation was analyzed in specimens of feline mammary tissue. A panel of specific anti-ck monoclonal antibodies (MAb) was used to determine ck distribution pattern in normal feline tissues (n = 3), and in benign (n = 18) and malignant (n = 20) feline mammary tumors. In selected tumors, the ck distribution pattern was also determined by biochemical methods. A MAb specific for α-smooth muscle actin was used to discriminate between myoepithelial cells and luminal epithelial cells.

In normal mammary gland tissues, 6 MAb reacted exclusively, either with myoepithelial cells or with luminal epithelial cells. Luminal epithelial cells reacted with MAb specific for ck typical of simple epithelia, whereas myoepithelial cells reacted with MAb specific for ck in basal cells of stratified epithelia. A similar distribution of ck was detected in specimens from benign tumors, except that ck4 was not detected in normal mammary gland tissues and was detected in some ducts in specimens with adenosis. Almost all tumor cells in specimens from malignant tumors reacted with MAb specific for ck typical of simple epithelia. Concomitant expression of ck typical of stratified epithelia was detected in small or large subpopulations of tumor cells in 70% of carcinomas. Cytokeratins typical of basal cell layers and typical for suprabasal layers of inner stratified epithelia were detected. Cytokeratins typical of stratified epithelia were always found in areas of squamous metaplasia, but also were found in adenocarcinomal cells surrounding these areas. We postulate that these adenocarcinoma cells represent transitional cells where the initial stages of squamous metaplasia have taken place, but squamous metaplasia is not yet detectable by light microscopy.

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