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.
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Dr. Zander reports grants from NRW Government during the conduct of the study; personal fees from Roche, personal fees from Novartis, personal fees from Lilly, personal fees from MSD, personal fees from BMS, personal fees from AstraZeneca, personal fees from Sanofi, outside the submitted work. All other authors declare that they have no conflict of interest.
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All procedures performed in the current study involving human tumor specimens were in accordance with ethical standards of the local research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board of the University Hospital of Cologne.
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The single protein immunohistochemical staining was performed during the regular pathological diagnostics and therefore no additional informed consent was obtained.
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The authors Patrick Sven Plum, Thomas Zander, Hakan Alakus, Alexander Quaas and Heike Loeser are members of the “Gastrointestinal Cancer Group Cologne (GCGC)”.
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Plum, P.S., Ulase, D., Bollschweiler, E. et al. 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, 1731–1739 (2018). https://doi.org/10.1007/s00432-018-2698-1
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DOI: https://doi.org/10.1007/s00432-018-2698-1