Increased c-myb mRNA expression in Barrett's esophagus and Barrett's-associated adenocarcinoma

Background. Esophageal adenocarcinoma develops through a multistage process which is characterized histopathologically by progression from Barrett's i ntestinal metaplasia to Barrett's esophagus with dysplasia and ultimately t o adenocarcinoma. The genetic basis of this process is increasingly well un derstood, but no studies have examined the role of the transcription factor c-myb in this disease. Material and methods. c-myb mRNA expression levels were measured using a qu antitative reverse transcription-polymerase chain reaction (RT-PCR) method in specimens of Barrett's intestinal metaplasia (n = 16), adenocarcinoma. ( n = 22), matching normal squamous esophagus tissues (n = 38), and normal sq uamous esophagus tissues from patients without Barrett's esophagus or chron ic gastroesophageal reflux disease (n = 10). Results. The median c-myb mRNA expression levels were significantly increas ed in Barrett's intestinal metaplasia tissues compared to normal esophagus tissues (P = 0.013) and in Barrett's-associated adenocarcinoma tissues comp ared to normal squamous esophagus tissues (P = 0.001). The c-myb expression levels increased progressively and significantly in histopathologically wo rse tissue types, with an increase from normal squamous esophagus mucosa to Barrett's intestinal metaplasia, and from Barrett's intestinal metaplasia to adenocarcinoma of the esophagus (P = 0.002). Median c-myb expression lev els were also significantly higher in histologically normal squamous esopha gus tissues from cancer patients compared to normal esophagus tissues from patients without cancer (P < 0.001) and a control group without evidence of Barrett's esophagus or gastroesophageal reflux disease (P = 0.003). Very h igh c-myb mRNA expression levels were found only in patients with cancer. Conclusion. These findings suggest that upregulation of c-myb mRNA expressi on is an early event in the development of Barrett's esophagus and associat ed adenocarcinoma, that high c-myb mRNA expression levels may be a clinical ly useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients wi th Barrett's-associated adenocarcinoma. (C) 2001 Academic Press.