The prognostic significance of biomaker expression in esophageal adenocarinoma

Abstract

The central aim of the thesis was to evaluate the prognostic significance of biological markers expressed in a tissue micro array (TMA) using immunohistochemistry (IHC) in patients that underwent esophagectomy due to esophageal adenocarcinoma (EAC). In the western world incidence of esophageal cancer is steadily increasing, mainly due to the increase in esophageal adenocarcinoma. Neoadjuvant chemoradiotherapy followed by esophagectomy now is the standard of care in Netherlands. It can be stated that introduction of minimally invasive techniques for esophagectomy (MIE) such as robotic-assisted esophagectomy and improvements in esophagectomy have optimized treatment of esophagectomy. Despite this optimal treatment still a subset of patients develops recurrence of disease. Therefore, further improvements might come from identification and eventually targeting of poor tumor characteristics already expressed in the primary tumor. In this thesis we focussed on expression of biological markers expressed in the primary tumor using a tissue micro array (TMA). All evaluated biological markers described in this thesis were involved in one or more important hallmarks of cancer such as: 1. Sustained proliferation; 2. Evading growth suppressors; 3. Tumor invasiveness and metastatic dissemination; 4. Replicative immortality; 5. Angiogenesis; and 6. Resisting cell death. All included patients were diagnosed with esophageal adenocarcinoma (EAC) and were non pre-treated. Of the corresponding pathological slides 3 representative tissue regions were selected and punched out from the complementary paraffin block containing the tumor. Subsequently, the biopsy cores (diameter 0.6mm) were transferred to a donor paraffin block. Using a TMA technique, all tumors could be evaluated simultaneously. With the exception of 2 studies, immunohistochemistry (IHC) was used to examine the immunoreactivity of various biological markers. The studies described in this thesis aim to evaluate the prognostic significance of various biological markers expressed in esophageal adenocarcinoma.