Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
Lars M. Schiffmann,
Heike Göbel,
Heike Löser,
Fabian Schorn,
Jan Paul Werthenbach,
Hans F. Fuchs,
Patrick S. Plum,
Marc Bludau,
Thomas Zander,
Wolfgang Schröder,
Christiane J. Bruns,
Hamid Kashkar,
Alexander Quaas,
Florian Gebauer
Affiliations
Lars M. Schiffmann
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC) and Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, CECAD Research Center
Heike Göbel
Center for Integrated Oncology (CIO) Cologne Bonn
Heike Löser
Center for Integrated Oncology (CIO) Cologne Bonn
Fabian Schorn
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC) and Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, CECAD Research Center
Jan Paul Werthenbach
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC) and Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, CECAD Research Center
Hans F. Fuchs
Department of General, Visceral and Cancer Surgery, University of Cologne
Patrick S. Plum
Department of General, Visceral and Cancer Surgery, University of Cologne
Marc Bludau
Department of General, Visceral and Cancer Surgery, University of Cologne
Thomas Zander
Center for Integrated Oncology (CIO) Cologne Bonn
Wolfgang Schröder
Department of General, Visceral and Cancer Surgery, University of Cologne
Christiane J. Bruns
Department of General, Visceral and Cancer Surgery, University of Cologne
Hamid Kashkar
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Center for Molecular Medicine Cologne (CMMC) and Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, CECAD Research Center
Alexander Quaas
Center for Integrated Oncology (CIO) Cologne Bonn
Florian Gebauer
Department of General, Visceral and Cancer Surgery, University of Cologne
Abstract Background Molecular markers predicting survival in esophageal adenocarcinoma (EAC) are rare. Specifically, in favorable oncologic situations, e.g. nodal negativity or major neoadjuvant therapy response, there is a lack of additional risk factors that serve to predict patients’ outcome more precisely. This study evaluated X-linked inhibitor of apoptosis protein (XIAP) as a potential marker improving outcome prediction. Methods Tissue microarrays from 362 patients that were diagnosed with resectable EAC were included in the study. XIAP was stained by immunohistochemistry and correlated to clinical outcome, molecular markers and markers of the cellular tumor microenvironment. Results XIAP did not impact on overall survival (OS) in the whole study collective. Subgroup analyses stratifying for common genetic markers (TP53, ERBB2, ARID1A/SWI/SNF) did not disclose any impact of XIAP expression on survival. Detailed subgroup analyses of [1] nodal negative patients, [2] highly T-cell infiltrated tumors and [3] therapy responders to neoadjuvant treatment revealed a significant inverse role of high XIAP expression in these specific oncologic situations; elevated XIAP expression detrimentally affected patients’ outcome in these subgroups. [1]: OS XIAP low: 202 months (m) vs. XIAP high: 38 m; [2]: OS 116 m vs. 28.2 m; [3]: OS 31 m vs. 4 m). Conclusions Our data suggest XIAP expression in EAC as a worthy tool to improve outcome prediction in specific oncologic settings that might directly impact on clinical diagnosis and treatment of EAC in the future.
