PS02.197: UPREGULATION OF IMP3 HAS A NEGATIVE PROGNOSTIC IMPACT IN EARLY INVASIVE ESOPHAGEAL ADENOCARCINOMA

Abstract

Abstract Background Despite improvements in perioperative treatments, the overall survival of patients with esophageal adenocarcinoma (EAC) remains low. In early invasive tumors (pT1) there is striking risk discrepancy for tumors with vascular invasion (L1/V1). As this tumor stage is potentially locally resectable, there is an urgent need for reliable pretherapeutical evaluation. High expression of IMP3 correlates with worse prognosis in colon and gastric cancer. In a small series of 30 patients with EAC, IMP3 is significantly associated with lymphovascular invasion. In our large cohort of EAC, we analyzed the immunohistochemical expression of IMP3 in correlation to clinical data. Methods 371 patients who underwent esophagectomy due to EAC at the Department of General, Visceral and Cancer Surgery, University of Cologne between 1999 and 2012 were included. Tissue Microarrays (TMA) were retrospectively established from the formalin-fixed, paraffin embedded material of the resected specimens and immunohistochemically stained using the primary antibody specific for IMP3. The IMP3 staining intensity was scored manually according to a 3-tier-scoring system (negative, weak and strong). Results TMAs from 371 patients were interpretable for further analysis. 109 patients (29.3%) had superficial EAC (pT1a/pT1b) while 262 (70.7%) showed locally advanced tumors (pT2 or pT3). 67 (26.7%) patients with advanced tumors and all pT1 EAC patients did not receive neoadjuvant therapy (chemotherapy or chemo-radiotherapy) prior to surgery. 259 of the 371 EAC revealed positive immunostaining for IMP3 including 167 strongly and 92 weakly positive. For patients without neoadjuvant therapy, there was a significant trend for higher IMP3 expression in early invasive tumors (pT1a/pT1b) showing significantly higher rates of IMP3 positive tumors compared to locally advanced pT3-tumors without neoadjuvant therapy (P = 0.0015). There was no difference of IMP3 expression according to neoadjuvant therapy in patients with pretreated EAC. There is a statistically significant association between IMP3 protein expression and shortened survival in early invasive pT1-esophageal carcinomas (P = 0.045). Conclusion IMP3 is a feasible marker in early invasive EAC (pT1a and pT1b) and is significantly associated with worse outcome. IMP3 indicates lymph node metastases, advanced infiltration depth and higher tumor grade. Thus IMP3 might be useful for therapeutic decisions in early invasive EAC. Disclosure All authors have declared no conflicts of interest.