Oncotarget

Research Papers:

Low BUB1 expression is an adverse prognostic marker in gastric adenocarcinoma

David Stahl, Martin Braun, Andrew J. Gentles, Philipp Lingohr, Adeline Walter, Glen Kristiansen and Ines Gütgemann _

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Oncotarget. 2017; 8:76329-76339. https://doi.org/10.18632/oncotarget.19357

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Abstract

David Stahl1, Martin Braun1, Andrew J. Gentles2, Philipp Lingohr3, Adeline Walter4, Glen Kristiansen1 and Ines Gütgemann1

1Institute of Pathology, University Hospital Bonn, Bonn, Germany

2Center for Cancer Systems Biology (CCSB), Stanford University, Stanford, California, USA

3Department of General, Visceral, Thoracic and Vascular Surgery, University Hospital Bonn, Bonn, Germany

4Department of Gynecology and Obstetrics, University Hospital Bonn, Bonn, Germany

Correspondence to:

Ines Gütgemann, email: [email protected]

Keywords: BUB1, immunohistochemistry, biomarker, gastric adenocarcinoma, gastric cancer

Received: March 17, 2017    Accepted: June 19, 2017    Published: July 18, 2017

ABSTRACT

Gastric adenocarcinomas are associated with a poor prognosis due to the fact that the tumor has often metastasized by the time of diagnosis and prognostic markers are urgently needed to tailor treatment.

We examined the expression of the mitotic spindle checkpoint protein BUB1 (budding uninhibited by benzimidazoles 1) and Ki-67 protein expression by immunohistochemistry in 218 patients with primary gastric adenocarcinomas.

Tumors with low frequency of BUB1 expression were associated with larger tumor size (pT) (p < 0.001), higher incidence of lymph node metastases (pN) (p = 0.027), distant metastases (pM) (p = 0.006) and higher UICC stage (p < 0.001). Furthermore, BUB1 expression was inversely correlated with residual tumor stage (p = 0.038). Abundant BUB1 protein expression correlated with frequent Ki-67 protein expression (p < 0.001) and low BUB1 expression was associated with shorter survival (p < 0.001). Univariate and multivariate analyses confirmed BUB1 to be an independent prognostic marker in gastric cancer (p = 0.021).


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