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Objectives: We followed The Cancer Genome Atlas (TCGA) grouping criteria and conducted a clinicopathological cohort study in a unique patient population to gain insight into the pathobiology of esophageal adenocarcinoma (EAC) and adenocarcinoma of the gastroesophageal junction (AGEJ). Methods: We studied and statistically compared the clinicopathological and prognostic features of both cancers in 303 consecutive patients treated at the Veterans Affairs Boston Healthcare System over a 20‐year period using uniform criteria and standardized routines. Results: Over 99% of patients were white men with a mean age of 69.1 years and an average body mass index (BMI) of 28.0 kg/m2. No significant differences were detected in age, gender, ethnicity, BMI, and history of tobacco abuse between the two groups. Compared to AGEJ patients, a significantly higher proportion of EAC patients had gastroesophageal reflux disease, long‐segment Barrett's esophagus, common adenocarcinoma type, smaller tumor size, better differentiation, more stages I or II but fewer stages III or IV diseases, scarcer lymph node invasion, fewer distant metastases, and better overall, disease‐free, and relapse‐free survival. The 5‐year overall survival rate was significantly higher in EAC patients than in AGEJ patients (41.3% vs 17.2%, P < 0.001). This improved survival among EAC patients remained significant after censoring all cases detected during endoscopic surveillance, suggesting different pathogenesis mechanisms between EAC and AGEJ. Conclusions: EAC patients showed significantly better outcomes than AGEJ patients. Our results require validation in other patient populations. [ABSTRACT FROM AUTHOR]

Ectopic expression of the gastrin-releasing peptide (GRP) receptor (GRP-R) occurs frequently in human malignancies of the gastrointestinal tract. Owing to paracrine and autocrine interaction with its specific high-affinity ligand GRP, tumor cell proliferation, migration, and invasion might ensue. Here we provide the first insights regarding molecular mechanisms of GRP-R regulation in gastrointestinal cancer cells. We identified by EMSA and chromatin immunoprecipitation assays two cAMP response element (CRE) binding sites that recruited transcription factor CRE binding protein (CREB) to the human GRP-R promoter. Transfection studies with a wild-type human GRP-R promoter reporter and corresponding CRE mutants showed that both CRE sites are critical for basal transcriptional activation in gastrointestinal cancer cells. Forced expression of cAMP-dependent effectors CREB and PKA resulted in robust upregulation of human GRP-R transcriptional activity, and this overexpression strictly required intact wild-type CRE sites. Direct cAMP stimulation with forskolin resulted in enhanced human GRP-R promoter activity only in HuTu-80 cells, but not in Caco-2 cells, coinciding with forskolin-induced CREB phosphorylation occurring only in HuTu-80 but not Caco-2 cells. In summary, CREB is a critical regulator of human GRP-R expression in gastrointestinal cancer and might be activated through different upstream intracellular pathways. regulatory peptide; bombesin; gastrointestinal cancer; cyclic AMP response element