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International Journal of Surgical Pathology
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Cell Discohesion and Multifocality of Carcinoma In situ of the Bladder: New Insight From the Adhesion Molecule Profile (e-Cadherin, Ep-CAM, and MUC1)

Carlo Patriarca, MD

Department of Pathology, Azienda Ospedaliera di Melegnano, Milan, carlo.patriarca{at}unimi.it

Piergiuseppe Colombo, MD

Department of Pathology, University of Milan Medical School, ICH Humanitas Rozzano, Milan

Angelo Pio Taronna, Dsc

Department of Experimental Medicine, University of Ferrara Medical School, Ferrara

Jelle Wesseling, MD, PhD

Department of Pathology, Netherlands Cancer Institute, NKI, Amsterdam, Netherlands

Giada Franchi, Dsc

Department of Pathology, University of Milan Medical School, ICH Humanitas Rozzano, Milan

Francesca Guddo, MD

Department of Pathology, Ospedale Cervello, Palermo, Italy

Richard Naspro, MD

Department of Urology, ICH Humanitas-Cliniche Gavazzeni, Bergamo Italy

Roberto Maria Macchi, MD

Department of Pathology, Azienda Ospedaliera di Melegnano, Milan

Paolo Giunta, MD

Department of Pathology, Azienda Ospedaliera di Melegnano, Milan

Marcello Di Pasquale, MD

Department of Pathology, Azienda Ospedaliera di Melegnano, Milan

Michele Parente, Dsc

Department of Pathology, Azienda Ospedaliera di Melegnano, Milan

Carmelo Arizzi, MD

Department of Pathology, Azienda Ospedaliera di Melegnano, Milan

Massimo Roncalli, MD, PhD

Department of Pathology, University of Milan Medical School, ICH Humanitas Rozzano, Milan

Biagio Campo, MD

Department of Urology, Azienda Ospedaliera di Melegnano, Milan

Urothelial cell carcinoma in situ (CIS) of the bladder is a superficially diffusive and highly discohesive disease. The authors analyzed the expression of some adhesion molecules (e-cadherin and Ep-CAM) and MUC1 in 32 unifocal and multifocal bladder urothelial cell CIS in an attempt to clarify this discohesion. E-cadherin was strongly expressed, in more than 75% of the cases. The presence of methylation of the CDH1 e-cadherin promoter gene was also investigated, but methylation was found in only one case. Ep-CAM was present in all the cases with a heterogeneous staining pattern. Similarly, MUC1/episialin was variously present in 94% of the cases without a polarized staining pattern and was expressed more strongly in cases with multifocal disease. Because loss of MUC1 polarization leads to interference with cell—cell adhesion mechanisms mediated by cadherins, these findings help explain why bladder urothelial cell CIS often shows a discohesive morphology and multifocality despite a strongly expressed adhesion molecule profile. Finally, Ep-CAM expression might provide some support for future target therapy trials.

Key Words: carcinoma in situ (CIS) • discohesion • bladder • urothelial cell carcinoma • MUC1 • e-cadherin

This version was published on April 1, 2009

International Journal of Surgical Pathology, Vol. 17, No. 2, 99-106 (2009)
DOI: 10.1177/1066896908326918


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