Universität zu Köln

Plum, Patrick Sven, Ulase, Dita, Bollschweiler, Elfriede, Chon, Seung-Hun ORCID: 0000-0002-8923-6428, Berlth, Felix, Zander, Thomas, Alakus, Hakan, Hoelscher, Arnulf H., Bruns, Christiane J., Schallenberg, Simon, Quaas, Alexander and Loeser, Heike (2018). Upregulation of insulin-like growth factor II mRNA-binding protein 3 (IMP3) has negative prognostic impact on early invasive (pT1) adenocarcinoma of the esophagus. J. Cancer Res. Clin. Oncol., 144 (9). S. 1731 - 1740. NEW YORK: SPRINGER. ISSN 1432-1335

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Abstract

Purpose Therapeutic decisions in esophageal adenocarcinomas (EAC) restricted to mucosa (pT1a) or submucosa (pT1b) depend mainly on classic histomorphology-based criteria like tumor grading or lymphovascular invasion with limited success. There is a strong need for reliable pre-therapeutical biomarker-based evaluation also applicable on endoscopically obtained biopsies. Methods Patients who underwent esophagectomy due to EAC in a high volume center between 1999 and 2016 were included. Tissue microarrays (TMA) were retrospectively established from the formalin-fixed and paraffin-embedded material of the resected specimens and immunohistochemically stained using a monoclonal primary antibody specific for IMP3. IMP3 staining intensity was scored manually according to a 3-tier-scoring system (negative, weak and strong). Results 371 EACs were interpretable for analysis. 109 patients (29%) had early invasive (pT1a/pT1b) and 262 patients (71%) locally advanced EAC (> pT2). 259 EACs (70%) revealed positive immunostaining for IMP3 including 167 strongly and 92 weakly positive. Early EAC had significantly lower IMP3 expression compared to advanced tumor stages (p < 0.0001). IMP3 positive pT1 EAC revealed higher levels of lymph node metastases (LNM) (p = 0.0001) and pT1b tumors showed higher rates of IMP3 positivity compared to pT1a (p = 0.007). Subdividing the submucosa in thirds, there was a significant trend for higher IMP3 expression with deeper tumor infiltration from pT1a to pT1b (sm3) (p = 0.0001). There was an association between IMP3 expression and shortened survival in pT1 EAC (p = 0.038). Conclusions IMP3 expression correlates with depth of tumor infiltration, rate of LNM and is associated with worse outcome. Thus, IMP3 might be useful for therapeutic decisions in early-invasive EAC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Plum, Patrick Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Ulase, Dita UNSPECIFIED UNSPECIFIED UNSPECIFIED Bollschweiler, Elfriede UNSPECIFIED UNSPECIFIED UNSPECIFIED Chon, Seung-Hun UNSPECIFIED orcid.org/0000-0002-8923-6428 UNSPECIFIED Berlth, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Alakus, Hakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, Arnulf H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruns, Christiane J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schallenberg, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Loeser, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-175845
DOI:	10.1007/s00432-018-2698-1
Journal or Publication Title:	J. Cancer Res. Clin. Oncol.
Volume:	144
Number:	9
Page Range:	S. 1731 - 1740
Date:	2018
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1335
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SQUAMOUS-CELL CARCINOMA; LYMPH-NODE METASTASIS; ONCOFETAL PROTEIN; THERAPEUTIC TARGET; BARRETTS-ESOPHAGUS; MOLECULAR-MARKER; CANCER; EXPRESSION; MUCOSAL; RISK Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17584