Upregulation of insulin-like growth factor II mRNA-binding protein 3 (IMP3) has negative prognostic impact on early invasive (pT1) adenocarcinoma of the esophagus

Patrick Sven Plum, Dita Ulase, Elfriede Bollschweiler, Seung Hun Chon, Felix Berlth, Thomas Zander, Hakan Alakus, Arnulf H. Hölscher, Christiane J. Bruns, Simon Schallenberg, Alexander Quaas, Heike Loeser

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1731-1739
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume144
Issue number9
DOIs
Publication statusPublished - Sep 2018

Keywords

  • Esophageal adenocarcinoma (EAC)
  • Immunohistochemistry (IHC)
  • IMP3
  • Prognosis
  • T1 esophageal cancer
  • Tissue microarray (TMA)

Field of Science

  • 3.2 Clinical medicine
  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

Fingerprint

Dive into the research topics of 'Upregulation of insulin-like growth factor II mRNA-binding protein 3 (IMP3) has negative prognostic impact on early invasive (pT1) adenocarcinoma of the esophagus'. Together they form a unique fingerprint.

Cite this