Increased expression of epidermal growth factor receptors in Barrett's esophagus associated with alkaline reflux: a putative model for carcinogenesis.

A 49-yr-old male was reviewed who had a 10-yr history of reflux esophagitis. He presented initially with frequent heartburn of moderate severity and, on subsequent endoscopy, was noted to have erosive esophagitis and, at that time, a high maximal gastric acid output. During the next 5 yr, his symptoms and acid output diminished. Eight years after presentation, he was noted to have developed a small area of Barrett's metaplasia, without dysplastic change. Ten years after the initial presentation he was completely asymptomatic, despite having extensive Barrett's metaplasia, now with high grade dysplasia. As a result, he was referred for esophagogastrectomy. At the time of surgery, he had alkaline reflux, with antacid gastric contents and, subsequently, hypochlorhydria was proven by a pentagastrin test. A second individual (male, 46 yr) who presented initially with reflux symptoms and gastric-type metaplasia, underwent gastric secretory studies that revealed a peak acid output of 16 mmol/L in 1986. During the period 1989 to 1991, his symptoms progressed despite H2 antagonist therapy. In this regard he was reinvestigated, and his peak acid output in 1991 was 0 mmol/L, and subsequent esophageal biopsies demonstrated intestinal metaplasia in four of six biopsies (two biopsies had high-grade dysplasia; the two others had gastric-type metaplasia). He has refused esophageal resection, and is being reviewed regularly at the endoscopy clinic. Flow cytometric analysis of the esophagus in both individuals revealed expression of epidermal growth factor receptor which was increased in the areas of high grade dysplasia, compared with Barrett's mucosa without dysplasia or normal cardiac mucosa. We conclude that alkaline reflux may accelerate the development of Barrett's esophagus (and intestinal type metaplasia) in patients with gastroesophageal reflux disease. The increased expressed of epidermal growth factor receptors in Barrett's mucosa with dysplasia compared with Barrett's mucosa without dysplasia may reflect the higher malignant potential of the former mucosa.