βIII-tubulin overexpression is linked to agressive tumor features and genetic instability in urinary bladder cancer
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βIII-tubulin overexpression is linked to agressive tumor features and genetic instability in urinary bladder cancer. / Hinsch, Andrea; Chaker, Aref; Burdelski, Christian; Koop, Christina; Tsourlakis, Maria Christina; Steurer, Stefan; Rink, Michael; Eichenauer, Till Simon; Wilczak, Waldemar; Wittmer, Corinna; Fisch, Margit; Simon, Ronald; Sauter, Guido; Büschek, Franziska; Clauditz, Till; Minner, Sarah; Jacobsen, Frank.
In: HUM PATHOL, Vol. 61, 03.2017, p. 210-220.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - βIII-tubulin overexpression is linked to agressive tumor features and genetic instability in urinary bladder cancer
AU - Hinsch, Andrea
AU - Chaker, Aref
AU - Burdelski, Christian
AU - Koop, Christina
AU - Tsourlakis, Maria Christina
AU - Steurer, Stefan
AU - Rink, Michael
AU - Eichenauer, Till Simon
AU - Wilczak, Waldemar
AU - Wittmer, Corinna
AU - Fisch, Margit
AU - Simon, Ronald
AU - Sauter, Guido
AU - Büschek, Franziska
AU - Clauditz, Till
AU - Minner, Sarah
AU - Jacobsen, Frank
N1 - Copyright © 2016. Published by Elsevier Inc.
PY - 2017/3
Y1 - 2017/3
N2 - Development of genetic instability is a hallmark of tumor progression. Type III ß-tubulin (TUBB3) is a component of microtubules involved in chromosome segregation. Its overexpression has been linked to adverse features of urinary bladder cancer. To investigate the role of TUBB3 for development of genetic instability, we compared TUBB3 expression with histopathological features and surrogate markers of genetic instability and tumor aggressiveness, copy number changes of HER2, TOP2A, CCND1, RAF1, and FGFR1, nuclear accumulation of p53, and cell proliferation, in a tissue microarray with >700 bladder cancers. TUBB3 expression was linked to high-grade and advanced stage cancers (P<.0001), rapid cell proliferation (P<.0001), presence of multiple gene copy number alterations (P=.0008), and nuclear accumulation of p53 (P=.0008). Strong TUBB3 staining was found in 43% of urothelial cancers harboring copy number alterations as compared to 28% of genetically stable cancers, and in 50% of p53-positive cancers as compared to 30% of p53-negative tumors. The fraction of tumors with concomitant TUBB3 and p53 positivity increased with tumor stage and grade: 2% in pTaG1-2, 11% in pTaG3, 17% in pT1G2, 23% in pT1G3, and 32% in pT2-4 cancers (P<.0001). Importantly, strong TUBB3 overexpression was detectable in about 20% of low-grade, non-invasive cancers. In summary, our study demonstrates that TUBB3 overexpression is linked to an aggressive subtype of urinary bladder cancers, which is characterized by increased genetic instability, p53 alterations, and rapid cell proliferation. Detection of TUBB3 overexpression in genetically stable, low-grade and non-invasive bladder cancers may be clinically useful to identify patients requiring particular close monitoring.
AB - Development of genetic instability is a hallmark of tumor progression. Type III ß-tubulin (TUBB3) is a component of microtubules involved in chromosome segregation. Its overexpression has been linked to adverse features of urinary bladder cancer. To investigate the role of TUBB3 for development of genetic instability, we compared TUBB3 expression with histopathological features and surrogate markers of genetic instability and tumor aggressiveness, copy number changes of HER2, TOP2A, CCND1, RAF1, and FGFR1, nuclear accumulation of p53, and cell proliferation, in a tissue microarray with >700 bladder cancers. TUBB3 expression was linked to high-grade and advanced stage cancers (P<.0001), rapid cell proliferation (P<.0001), presence of multiple gene copy number alterations (P=.0008), and nuclear accumulation of p53 (P=.0008). Strong TUBB3 staining was found in 43% of urothelial cancers harboring copy number alterations as compared to 28% of genetically stable cancers, and in 50% of p53-positive cancers as compared to 30% of p53-negative tumors. The fraction of tumors with concomitant TUBB3 and p53 positivity increased with tumor stage and grade: 2% in pTaG1-2, 11% in pTaG3, 17% in pT1G2, 23% in pT1G3, and 32% in pT2-4 cancers (P<.0001). Importantly, strong TUBB3 overexpression was detectable in about 20% of low-grade, non-invasive cancers. In summary, our study demonstrates that TUBB3 overexpression is linked to an aggressive subtype of urinary bladder cancers, which is characterized by increased genetic instability, p53 alterations, and rapid cell proliferation. Detection of TUBB3 overexpression in genetically stable, low-grade and non-invasive bladder cancers may be clinically useful to identify patients requiring particular close monitoring.
U2 - 10.1016/j.humpath.2016.11.005
DO - 10.1016/j.humpath.2016.11.005
M3 - SCORING: Journal article
C2 - 28025079
VL - 61
SP - 210
EP - 220
JO - HUM PATHOL
JF - HUM PATHOL
SN - 0046-8177
ER -
