GEJ adenocarcinoma occurs most commonly in patients in their 6th-7th decade and is uncommon before age of 40 years. While certain clinical, pathological, and molecular features of GEJ adenocarcinoma in older patients have been extensively studied, they remain to be determined in the younger population. We evaluated 608 patients admitted to surgery for GEJ adenocarcinoma and stratified them into 2 age-groups of < 40 and > 50 years, respectively. We compared their demographics, tobacco exposure, clinicopathological features, treatment strategies, and prognosis. Fluorescence in situ hybridization (FISH) with selected DNA probes of Y chromosome was investigated in selected male patients with the focus on uninvolved squamous mucosa, intestinal metaplasia, glandular dysplasia, and adenocarcinoma. Probes for centromeres of Y chromosome were hybridized to formalin fixed and paraffin embedded tissue sections and a minimum of 100 cells were enumerated for each histopathologic pattern. The clinical and pathologic characteristics are summarized in Table 1. There was no difference in the surgical techniques applied in the two age groups and most patients underwent Ivor Lewis esophagectomy. The only statistically significant finding was the higher frequency of tobacco smoking in the older patients. Table 2 demonstrates a progressive loss of Y chromosome from benign squamous epithelium to Barrett’s mucosa and dysplasia, and, ultimately, to a nearly complete loss in adenocarcinoma. While there was a trend of more losses of Y chromosome during this pathologic progression in older patients, they did not a reach statistical significance. In conclusion, when compared with the older age-group, young patients with GEJ adenocarcinoma possess similar known clinical and pathologic characteristics. The commonly detected genetic aberration of progressive Y chromosomal loss is also present in the younger patients. Possible additional molecular alterations responsible for the accelerated neoplastic process in young patients are being investigated.
Table 1

GERD - Gastroesophageal Reflux Disease DFS - Disease Free Survival OS - Overall Survival NS - not significant
Table 2. Results of FISH for the Detection of Y chromosome Loss