TY - JOUR
T1 - PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder
AU - Plage, Henning
AU - Furlano, Kira
AU - Hofbauer, Sebastian
AU - Roßner, Florian
AU - Schallenberg, Simon
AU - Elezkurtaj, Sefer
AU - Lennartz, Maximilian
AU - Marx, Andreas
AU - Samtleben, Henrik
AU - Fisch, Margit
AU - Rink, Michael
AU - Slojewski, Marcin
AU - Kaczmarek, Krystian
AU - Ecke, Thorsten
AU - Klatte, Tobias
AU - Koch, Stefan
AU - Adamini, Nico
AU - Minner, Sarah
AU - Simon, Ronald
AU - Sauter, Guido
AU - Weischenfeldt, Joachim
AU - Schlomm, Thorsten
AU - Horst, David
AU - Zecha, Henrik
AU - Kluth, Martina
AU - Weinberger, Sarah
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Biomarker
KW - Bladder Cancer
KW - PLAP
KW - Prognosis
KW - Tissue Micro Array
U2 - 10.1007/s11255-024-04319-8
DO - 10.1007/s11255-024-04319-8
M3 - Journal article
C2 - 39680294
AN - SCOPUS:85212190036
JO - International Urology and Nephrology
JF - International Urology and Nephrology
SN - 0301-1623
ER -