Large-scale human tissue analysis identifies Uroplakin 1a as a putative diagnostic marker for urothelial cancer
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Large-scale human tissue analysis identifies Uroplakin 1a as a putative diagnostic marker for urothelial cancer. / Reiswich, Viktor; Könemann, Steffi; Lennartz, Maximilian; Höflmayer, Doris; Menz, Anne; Chirico, Viktoria; Hube-Magg, Claudia; Fraune, Christoph; Bernreuther, Christian; Simon, Ronald; Clauditz, Till S; Sauter, Guido; Hinsch, Andrea; Kind, Simon; Jacobsen, Frank; Steurer, Stefan; Minner, Sarah; Büscheck, Franziska; Burandt, Eike; Marx, Andreas H; Lebok, Patrick; Krech, Till.
In: PATHOL RES PRACT, Vol. 237, 154028, 09.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Large-scale human tissue analysis identifies Uroplakin 1a as a putative diagnostic marker for urothelial cancer
AU - Reiswich, Viktor
AU - Könemann, Steffi
AU - Lennartz, Maximilian
AU - Höflmayer, Doris
AU - Menz, Anne
AU - Chirico, Viktoria
AU - Hube-Magg, Claudia
AU - Fraune, Christoph
AU - Bernreuther, Christian
AU - Simon, Ronald
AU - Clauditz, Till S
AU - Sauter, Guido
AU - Hinsch, Andrea
AU - Kind, Simon
AU - Jacobsen, Frank
AU - Steurer, Stefan
AU - Minner, Sarah
AU - Büscheck, Franziska
AU - Burandt, Eike
AU - Marx, Andreas H
AU - Lebok, Patrick
AU - Krech, Till
N1 - Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - Uroplakin 1A (Upk1a) protein is relevant for stabilizing and strengthening urothelial cells and helps to prevent them from rupturing during bladder distension. Based on RNA expression data Upk1a is expressed in a limited number of normal tissues and tumors. To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1a immunohistochemistry, a tissue microarray containing 6929 samples from 115 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed. Upk1a positivity was found in 34 (29.6 %) different tumor types including 9 (7.8 %) tumor types with at least one strongly positive case. The highest rates of Upk1a positivity were seen in various subtypes of urothelial neoplasms (42.6-98 %) including Brenner tumors of the ovary (64.9 %) followed by neoplasms of the thyroid (10.4-33.3 %). In urothelial tumors, Upk1a staining predominated at the cell membranes and staining intensity was often moderate to strong. In thyroidal neoplasms the staining was mostly purely cytoplasmic and of low to moderate intensity. Upk1a positivity was also seen in up to 15 % of cases in 25 additional tumor categories but the staining intensity was often cytoplasmic and the intensity was usually judged as weak and only rarely as moderate. Within non-invasive (pTa) tumors, the Upk1a positivity rate decreased from 94 % in pTa G2 (low grade) to 90.1 % in pTa G3 (p = 0.012) and was even lower in muscle-invasive carcinomas (41.5 %; p < 0.0001 vs pTaG3). Within muscle invasive carcinomas, Upk1a expression was unrelated to nodal metastasis (p > 0.05) and patient outcome (p > 0.05). In conclusion, Upk1a immunohistochemistry is a potentially useful and specific diagnostic marker for the distinction of urothelial carcinomas from other neoplasms. However, its sensitivity is less than 50 % in muscle-invasive cancers because Upk1a expression decreases during grade and stage progression.
AB - Uroplakin 1A (Upk1a) protein is relevant for stabilizing and strengthening urothelial cells and helps to prevent them from rupturing during bladder distension. Based on RNA expression data Upk1a is expressed in a limited number of normal tissues and tumors. To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1a immunohistochemistry, a tissue microarray containing 6929 samples from 115 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed. Upk1a positivity was found in 34 (29.6 %) different tumor types including 9 (7.8 %) tumor types with at least one strongly positive case. The highest rates of Upk1a positivity were seen in various subtypes of urothelial neoplasms (42.6-98 %) including Brenner tumors of the ovary (64.9 %) followed by neoplasms of the thyroid (10.4-33.3 %). In urothelial tumors, Upk1a staining predominated at the cell membranes and staining intensity was often moderate to strong. In thyroidal neoplasms the staining was mostly purely cytoplasmic and of low to moderate intensity. Upk1a positivity was also seen in up to 15 % of cases in 25 additional tumor categories but the staining intensity was often cytoplasmic and the intensity was usually judged as weak and only rarely as moderate. Within non-invasive (pTa) tumors, the Upk1a positivity rate decreased from 94 % in pTa G2 (low grade) to 90.1 % in pTa G3 (p = 0.012) and was even lower in muscle-invasive carcinomas (41.5 %; p < 0.0001 vs pTaG3). Within muscle invasive carcinomas, Upk1a expression was unrelated to nodal metastasis (p > 0.05) and patient outcome (p > 0.05). In conclusion, Upk1a immunohistochemistry is a potentially useful and specific diagnostic marker for the distinction of urothelial carcinomas from other neoplasms. However, its sensitivity is less than 50 % in muscle-invasive cancers because Upk1a expression decreases during grade and stage progression.
U2 - 10.1016/j.prp.2022.154028
DO - 10.1016/j.prp.2022.154028
M3 - SCORING: Journal article
C2 - 35872365
VL - 237
JO - PATHOL RES PRACT
JF - PATHOL RES PRACT
SN - 0344-0338
M1 - 154028
ER -