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. 2025 May;57(5):1381-1388.
doi: 10.1007/s11255-024-04319-8. Epub 2024 Dec 16.

PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder

Henning Plage  1 , Kira Furlano  2 , Sebastian Hofbauer  2 , Florian Roßner  3 , Simon Schallenberg  3 , Sefer Elezkurtaj  3 , Maximilian Lennartz  4 , Andreas Marx  5 , Henrik Samtleben  5 , Margit Fisch  6 , Michael Rink  7 , Marcin Slojewski  8 , Krystian Kaczmarek  8 , Thorsten Ecke  9 , Tobias Klatte  9 , Stefan Koch  10 , Nico Adamini  11 , Sarah Minner  4 , Ronald Simon  4 , Guido Sauter  4 , Joachim Weischenfeldt  2   12   13 , Thorsten Schlomm  2 , David Horst  3 , Henrik Zecha  2   11 , Martina Kluth  4 , Sarah Weinberger  2
Affiliations

PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder

Henning Plage et al. Int Urol Nephrol. 2025 May.

Abstract

Purpose: Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.

Results: PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p < 0.0001). Within pT2-4 carcinomas, PLAP staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence-free survival, and cancer-specific survival (p > 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p < 0.0001), and p63 expression loss (p = 0.0456).

Conclusion: In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.

Keywords: Biomarker; Bladder Cancer; PLAP; Prognosis; Tissue Micro Array.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The use of archived remnants of diagnostic tissues for manufacturing of TMAs and their analysis for research purposes as well as patient data analysis has been approved by local laws (HmbKHG, §12) and by the local ethics committee (Ethics commission Hamburg, WF-049/09). All work has been carried out in compliance with the Helsinki Declaration.

Figures

Fig. 1
Fig. 1
Pattern of PLAP immunostaining in urothelial carcinomas. The panels show a strong predominantly membranous PLAP staining in most cells of two muscle-invasive urothelial carcinomas (A, B), a membranous and cytoplasmic PLAP positivity of variable intensity in most cells of a pT2-4 carcinoma (C), a weak to moderate predominantly cytoplasmic PLAP positivity of a small subset of tumor cells in a pT2-4 urothelial carcinoma (D), and a strong, predominantly membranous PLAP positivity which is largely restricted to the stroma adjacent tumor cell layer in two other pT2-4 carcinomas (E, F). PLAP immunostaining is absent in a pT2-4 carcinoma (G) and in a pTaG2 low grade tumor (H)
Fig. 2
Fig. 2
PLAP immunostaining and prognosis in muscle-invasive urothelial carcinomas. A Overall survival, B recurrence-free survival, and C cancer-specific survival
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