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Different immunohistochemical and ultrastructural phenotypes of squamous differentiation in bladder cancer

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Abstract

Besides worse prognosis of bladder cancer with squamous differentiation (pure squamous cell carcinoma (SCC) or mixed urothelial carcinoma (UC/SCC)), high-grade non-keratinising squamous differentiation is difficult to identify in haematoxylin–eosin stainings. This study aims to validate routine immunohistochemical markers for squamous differentiation in a larger cohort of patients. Tissue microarrays of 89 pure SCCs and mixed UC/SCCs, 66 urothelial carcinomas (UC), precursor lesions and normal urothelium were stained for cytokeratin (CK) 5/6, CK 5/14, CK 7, CK 20 and uroplakin III. Electron microscopy was performed to confirm the differentiation. Pure SCCs displayed staining throughout the epithelium for CK 5/6 (76.6% (36/47)) and CK 5/14 (95.8% (46/48)), focal staining for CK 7 (28.9% (13/45)) and no staining for CK 20 and uroplakin III (both 0% (0/48)). UCs exhibited a basal or diffuse staining for CK 5/6 (30.2% (16/53)) and CK 5/14 (57.1% (32/56)), focal positivity for CK 7 (83.6% (46/55)), CK 20 (50.9% (29/57)) and uroplakin III (21.8% (12/55)). Each marker discriminated SCC and UC significantly (p < 0.01). A third subgroup rarely showed full epithelial staining for CK 5/6 (14.3% (1/7)) and CK 5/14 (28.6% (2/7)), focal staining for CK 7 (85.7% (6/7)) and no staining for CK 20 and uroplakin III (both 0% (0/7)). Electron microscopy could prove both, SCC and UC characteristics, revealing a transient type. A staining pattern with CK 5/6- and CK 5/14-positivity plus CK 20- and uroplakin III-negativity identified squamous differentiation in bladder tumours and revealed a third type of squamous transdifferentiation.

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Acknowledgement

The authors are grateful to Stella Koufou for the sample recruitment and to Marina Molitor as well as Ursula Schneider for the technical support. Furthermore, they like to thank Daniela Smeets, Hiltrud Königs and Rudolf Jung for the excellent sample preparation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany

    Nadine T. Gaisa, Till Braunschweig, Nina Reimer & Ruth Knuechel

  2. Electron Microscopic Facility, RWTH Aachen University, Aachen, Germany

    Jörg Bornemann

  3. Institute of Pathology Saarbruecken-Rastpfuhl, Saarbruecken, Germany

    Elke Eltze

  4. Institute of Pathology LMU Munich, Munich, Germany

    Sabine Siegert

  5. Institute of Pathology, University Dresden, Dresden, Germany

    Marieta Toma

  6. Division of Nephrology, University Hospital RWTH Aachen, Aachen, Germany

    Luigi Villa

  7. Institute of Pathology, University Hospital Erlangen, Erlangen, Germany

    Arndt Hartmann

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  1. Nadine T. Gaisa
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  2. Till Braunschweig
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  3. Nina Reimer
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  7. Marieta Toma
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  8. Luigi Villa
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  9. Arndt Hartmann
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  10. Ruth Knuechel
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Correspondence to Ruth Knuechel.

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Gaisa, N.T., Braunschweig, T., Reimer, N. et al. Different immunohistochemical and ultrastructural phenotypes of squamous differentiation in bladder cancer. Virchows Arch 458, 301–312 (2011). https://doi.org/10.1007/s00428-010-1017-2

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  • DOI: https://doi.org/10.1007/s00428-010-1017-2

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