Abstract
IntroductionA striking epidemiological feature of esophageal adenocarcinoma (EAC) is its strong, unexplained male predominance but few studies have evaluated the prevalence of sex hormone receptor expression in EAC.ResultsA low proportion of EAC tumors stained positive for ERα (4%) and AR (3%) while approximately one third stained positive for ERβ (31%). After a mean follow-up of 3 years (max 9 years), no significant associations were seen for ERα, ERβ or AR expression and EAC recurrence or survival. A non-significant reduction in mortality was observed for positive ERβ tumor expression, when restricting to patients with gastro-esophageal junctional (GEJ) cancer (HR 0.58, 95% CI 0.33, 1.03, p = 0.06).Materials and MethodsWe identified all EAC patients who underwent neo-adjuvant chemotherapy prior to surgical resection between 2004–2012 in the Northern Ireland Cancer Centre. Immunohistochemical expression of ERα, ERβ and AR was scored on triplicate cores to generate H-scores. Cox proportional hazards regression was used to evaluate the association between sex hormone receptor expression and overall, cancer-specific and recurrence-free survival.ConclusionWe found little evidence of ERα or AR expression in EAC. A moderate proportion expressed ERβ and there was suggestive evidence that its expression was associated with improved survival in GEJ cancer patients.
Highlights
A striking epidemiological feature of esophageal adenocarcinoma (EAC) is its strong, unexplained male predominance but few studies have evaluated the prevalence of sex hormone receptor expression in EAC
A total of 158 formalinfixed paraffin embedded (FFPE) EAC resection specimens were collected from the Northern Ireland Cancer Centre
In a population-representative study of EAC patients who underwent neoadjuvant chemotherapy prior to surgical resection, we found little evidence of ERα or Androgen receptor (AR) expression in EAC while expression of ERβ was identified in approximately one third of tumors
Summary
A striking epidemiological feature of esophageal adenocarcinoma (EAC) is its strong, unexplained male predominance but few studies have evaluated the prevalence of sex hormone receptor expression in EAC. The most striking epidemiological feature of EAC is its strong unexplained male predominance [7,8,9], with male-to-female incidence ratios of up to 6:1 observed [10, 11]. This has led to the suggestion of sex hormone involvement in EAC development, possibly via estrogenic protection, a detrimental effect of androgens, or both [12, 13]. Androgen receptor (AR) is a key mediator of inflammatory signals in esophageal cancer progression and its expression has been shown to promote cell migration, invasion and proliferation in esophageal cancer in vivo [13, 20]
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