Lgr5 and stem/progenitor gene expression in gastric/gastroesophageal junction carcinoma – significance of potentially retained stemness

Background Gastric/gastroesophageal junction (GEJ) adenocarcinomas are heterogeneous, comprising four molecularly distinct subtypes, namely EBV-positive, microsatellite instability (MSI), chromosomal instability (CIN) and genomically stable (GS) subtypes, and a part of this heterogeneity may hypothesized to be different cells-of-origin. Stem/progenitor cell hierarchy in the stomach is complex, which include the Lgr5(+) gastric stem cells (GSCs). Methods While previous studies have focused on non-nuclear Lgr5 expression, nuclear Lgr5 expression has been reported in a subset of stem cells, and we examined nuclear Lgr5 expression in a local cohort of 95 cases of gastric/GEJ adenocarcinoma. mRNA levels for LGR5 and other stem cell marker genes were examined in the TCGA cohort. Results We observed nuclear Lgr5 expression in a 18/95 cases. Near mutual exclusivity was seen between nuclear Lgr5 and strong non-nuclear Lgr5. Both strong non-nuclear and nuclear Lgr5 expression tended to be seen more frequently with the intestinal histotype and approximated CIN molecular subtype. With respect to overall survival (OS), nuclear Lgr5 expression appears to be protective, with the worst survival being seen in the cases lacking nuclear Lgr5 and with low non-nuclear Lgr5 expression. When compared to other stem/progenitor cell markers, LGR5 mRNA expression clusters with other GSC marker genes, including VIL1. Higher expression of these GSC marker genes was associated with better OS. Conclusions Our results show that Lgr5 expression is dynamic in gastric/GEJ adenocarcinoma and heterogeneous across the several disease attributes. We postulate that this may reflect “retained stemness” in the form of Lgr5High-GSC signature that appears to be associated with better survival.

P14 THE IMPACT OF TRANSTHORACIC AND TRANSHIATAL ESOPHAGECTOMY ON LONG-TERM QUALITY OF LIFE ACCORDING TO EORTC QLQ-C30 AND EORTC QLQ-OG25 QUESTIONNAIRES

Aim The aim of this study was to evaluate long-term HR-QoL in patients undergoing transhiatal versus transthoracic esophagectomy in a tertiary referral center. Background & Methods Treatment of esophageal cancers is challenging. Besides (neo)adjuvant chemo(radio)therapy different surgical approaches are possible such as transhiatal (THE) or transthoracic esophagectomy (TTE) with a cervical or intrathoracic anastomosis. Studies have been performed to establish evidence which is the preferred procedure in terms of postoperative morbidity, survival and short- and long-term health-related quality of life (HR-QoL). All patients after THE or TTE for distal esophageal or gastroesophageal junction carcinoma performed between 2003 and 2016 received EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. All questionnaires with a follow-up of more than two years after surgery were analysed. Three HR-QoL domains were chosen as primary endpoints: problems with eating, reflux and nausea and vomiting. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. The results were corrected for possible confounders such as age and gender. Results The questionnaire response rate was 47.6%, with 56 patients in the THE group and 134 in the TTE group. The mean age was 63.5 years and a median follow-up of 3.7 years (range 24-137 months) was reached. No significant difference was found in any of the HR-QoL domains or postoperative complications between the two groups. Significantly more lymph nodes were resected in the TTE group (p<0.001). No difference was found in the lymph node metastases or radicality of surgery between the two groups. Conclusion After a long follow-up of more than two years no differences in HR-QoL or postoperative complications were found between patients with distal esophageal or gastroesophageal junction carcinoma undergoing THE or TTE esophagectomy. Based on this study we conclude that long-term quality of life should not influence the decision making for surgical approach between THE and TTE esophagectomy.