Gastric cancer is the second most common cause of cancer-related death worldwide, and the incidence of esophageal adenocarcinoma is rising. While some progress has been made in treatment strategies, overall survival remains very poor for patients with adenocarcinoma in the upper gastrointestinal tract. Special AT-rich sequence binding protein 1 (SATB1) is a global genome organizer that has been demonstrated to promote aggressive tumor behavior in several different types of cancer, including gastric cancer. The prognostic value of SATB1 expression in esophageal cancer has, however, not yet been described. In this study, expression of SATB1 was examined by immunohistochemistry on tissue microarrays prepared from tissue samples from 175 patients with adenocarcinoma of the esophagus, cardia, or stomach and containing normal tissue, intestinal metaplasia, primary tumors, and metastases. A well-validated antibody was used. We found SATB1 to be an independent prognostic factor in patients with a radically resected tumor, correlating with shorter overall survival as well as with shorter recurrence-free survival. SATB1 expression was also found to be significantly lower in primary tumors associated with intestinal metaplasia than those without intestinal metaplasia. This observation is of potential biological interest as it has been proposed that intestinal metaplasia-associated tumors constitute a less aggressive phenotype.

The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract.

Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma.

The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed.

Perioperative chemotherapy enhances the survival rates for patients with esophageal and gastric (EG) adenocarcinoma, but not all patients benefit from this additional treatment. Chemotherapeutic agents have been demonstrated to alter the immune cell (IC) composition in the tumor microenvironment. Hence, there is a rationale to investigate the influence of neoadjuvant chemotherapy (NAC) on different IC subsets, to better understand and compare their utility as complementary prognostic or predictive biomarkers in a clinically relevant context. The density of T cells (CD8+ and FoxP3+), B cells (CD20+) and the expression of PD-L1 on ICs and tumor cells (TC) was assessed by immunohistochemistry on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. The cohort encompasses 148 patients with resectable EG adenocarcinoma, all of whom received NAC. The density of CD8+ cells was decreased and the density of FoxP3+ cells and CD20+ cells was increased in PT post-NAC. PD-L1 expression was not altered following NAC. In pre-NAC specimens, high FoxP3+ density and high PD-L1 expression on ICs were favorable prognostic factors, whereas high CD8+ density was an unfavorable prognostic factor. In post-NAC specimens, however, high FoxP3+ density was an unfavorable prognostic factor, and high PD-L1 expression on TC was associated with a shorter survival. There were no significant associations between IC density or PD-L1 expression in PT pre-NAC and histopathological regression. These findings propose that NAC might alter the density and prognostic impact of some IC subsets in EG adenocarcinoma.

Background: Despite improvements in surgical methodologies and perioperative chemo- and radiotherapy, the prognosis for patients with esophageal and gastric cancer remains poor. Hence, there is a great need to identify complementary biomarkers for improved treatment stratification. Tumor-infiltrating immune cells have been shown to impact on outcome in many types of cancer, including gastroesophageal cancer. The aim of this present study was to examine the prognostic value of tumor-infiltrating macrophages in gastroesophageal adenocarcinoma. Methods: The density of CD68+, CD163+, and MARCO+ macrophages was assessed by immunohistochemistry on tissue microarrays with primary tumors from a consecutive, retrospective cohort of 174 patients with treatment-naïve gastroesophageal adenocarcinoma. Total densities and infiltration in tumor nest (TN) were denoted as none/sparse (0), intermediate (1), or high (2). The impact on overall survival (OS) was examined by Kaplan-Meier analysis, log-rank test, and Cox proportional hazards modeling. Results: Increased infiltration of both CD68+ and CD163+, but not MARCO+, macrophages in TN was significantly associated with a stepwise reduced survival. Median OS for patients with none/sparse, intermediate, and high CD68+ TN infiltration was 4.4, 2.6, and 1.0 years, respectively. Median OS for patients with none/sparse, intermediate, and high CD163+ TN infiltration was 4.4, 2.2, and 1.1 years, respectively. High infiltration of CD68+ macrophages remained an independent prognostic factor in adjusted analysis (hazard ratio = 1.61, 95% confidence interval = 1.02-2.55, and p = 0.041). Conclusion: Infiltration of CD68+ and CD163+, but not MARCO+, macrophages is prognostic for OS in gastroesophageal adenocarcinoma. The relevance of this finding in clinical practice remains to be elucidated.

Background: The outlook for patients with esophageal and gastric (EG) cancer remains poor. Hence, there is a compelling need to identify novel treatment strategies and complementary biomarkers. Programmed death ligand 1 (PD-L1) and mismatch repair deficiency (dMMR) are putative biomarkers of response to immune-checkpoint blockade, but their prognostic value and interrelationship in EG cancer have been sparsely investigated. Methods: Immunohistochemical expression of PD-L1 on tumour cells (TC) and tumour-infiltrating immune cells (TIC), and of PD-1 (programmed death receptor 1) on TIC was assessed using tissue microarrays with primary tumours and a subset of paired lymph node metastases from a consecutive, retrospective cohort of 174 patients with chemoradiotherapy-naïve EG adenocarcinoma. MMR proteins MLH1, PMS2, MSH2, and MSH6 were assessed by immunohistochemistry. The total number (intratumoural, tumour-adjacent, and stromal) of CD8+ T cells in each core was calculated by automated analysis. Results: High PD-L1 expression on both TC and TIC, but not PD-1 expression, was significantly associated with dMMR. PD-L1 expression on TIC was significantly higher in lymph node metastases than in primary tumours. High expression of PD-L1 or PD-1 on TIC was significantly associated with a prolonged survival, the former independently of established prognostic factors. A significant stepwise positive association was found between CD8+ T cells and categories of PD-L1 expression on TIC. Conclusion: PD-L1 expression on TIC is higher in lymph node metastases compared to primary tumours, correlates with dMMR, and is an independent factor of prolonged survival in patients with chemoradiotherapy-naïve EG adenocarcinoma. These findings suggest that PD-L1 expression on TIC may be a useful biomarker for identifying patients who may not need additional chemo- or chemoradiotherapy, and who may benefit from PD-1/PD-L1 immune-checkpoint blockade.

Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.