Different immunohistochemical and ultrastructural phenotypes of squamous differentiation in bladder cancer.
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.
Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Nadine T
NT
Gaisa
Till
T
Braunschweig
Nina
N
Reimer
Jörg
J
Bornemann
Elke
E
Eltze
Sabine
S
Siegert
Marieta
M
Toma
Luigi
L
Villa
Arndt
A
Hartmann
Ruth
R
Knuechel
D014408:Biomarkers, Tumor / Q000378:metabolism; D002278:Carcinoma in Situ / Q000378:metabolism / Q000648:ultrastructure*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000648:ultrastructure*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000648:ultrastructure*; D002452:Cell Count; D002454:Cell Differentiation; D015653:Cystectomy; D006801:Humans; D007633:Keratins / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000648:ultrastructure*; D019459:Urothelium / Q000378:metabolism / Q000648:ultrastructure
D014408:Biomarkers, Tumor; D007633:Keratins