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

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2024年12月16日

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Henning Plage,
Kira Furlano,
Sebastian Hofbauer,
Florian Roßner,
Simon Schallenberg,
Sefer Elezkurtaj,
Maximilian Lennartz,
Andreas Marx,
Henrik Samtleben,
Margit Fisch,
Michael Rink,
Marcin Slojewski,
Krystian Kaczmarek,
Thorsten Ecke,
Tobias Klatte,
Stefan Koch,
Nico Adamini,
Sarah Minner,
Ronald Simon,
Guido Sauter,
Joachim Weischenfeldt,
Thorsten Schlomm,
David Horst,
Henrik Zecha,
Martina Kluth,
Sarah Weinberger

摘要

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.