Plage Henning, Furlano Kira, Hofbauer Sebastian, Roßner Florian, Schallenberg Simon, Elezkurtaj Sefer, Lennartz Maximilian, Marx Andreas, Samtleben Henrik, Fisch Margit, Rink Michael, Slojewski Marcin, Kaczmarek Krystian, Ecke Thorsten, Klatte Tobias, Koch Stefan, Adamini Nico, Minner Sarah, Simon Ronald, Sauter Guido, Weischenfeldt Joachim, Schlomm Thorsten, Horst David, Zecha Henrik, Kluth Martina, Weinberger Sarah
Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.
Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin and, Berlin Institute of Health, Berlin, Germany.
Int Urol Nephrol. 2025 May;57(5):1381-1388. doi: 10.1007/s11255-024-04319-8. Epub 2024 Dec 16.
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.
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).
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.
胎盘碱性磷酸酶（PLAP）是一种功能尚不清楚的蛋白质，通常仅在胎盘中表达。在癌症中，PLAP表达是生殖细胞肿瘤的一个标志，但也可出现在尿路上皮癌中。为评估PLAP表达在膀胱癌中的潜在临床意义，方法：采用免疫组织化学方法在组织芯片上分析了2500多例尿路上皮膀胱癌中的PLAP蛋白。
正常尿路上皮细胞中未观察到PLAP染色，但在15.9%的尿路上皮癌中观察到PLAP染色，其中282例（11.5%）为弱阳性，57例（2.3%）为中度阳性，51例（2.1%）为强阳性。在413例pTa G2低级别肿瘤中，PLAP阳性率为4.1%；在176例pTa G2高级别肿瘤中为10.2%；在97例pTa G3肿瘤中为7.2%（p = 0.0636）。与pTa肿瘤相比，1341例pT2 - 4期癌的PLAP阳性率明显更高（19.8%，p < 0.0001）。在pT2 - 4期癌中，PLAP染色与pT、pN、分级、L状态、V状态、总生存期、无复发生存期和癌症特异性生存期均无关（p > 0.25）。然而，PLAP阳性与p16阳性（p = 0.0185）、GATA3阳性（p < 0.0001）和p63表达缺失（p = 0.0456）相关。
总之，这些数据表明PLAP在相当一部分pT2 - 4期尿路上皮癌中表达，与癌症侵袭性无关，但与特定分子特征相关。一旦抗PLAP癌症药物生效，尿路上皮癌是临床评估的候选肿瘤实体。
