Expression of acidic fibroblast growth factor in Barrett's esophagus and associated esophageal adenocarcinoma.

OBJECTIVE

Adenocarcinoma of the esophagus is generally attributed to the neoplastic transformation of intestinal metaplastic lesions (Barrett's esophagus). On the basis of our preliminary data that showed significant acidic fibroblast growth factor mRNA and protein expression in adenocarcinoma of the esophagus, we studied expression of fibroblast growth factor in esophageal adenocarcinoma and its precursor lesions, intestinal metaplasia, low-grade dysplasia, and high-grade dysplasia. Fibroblast growth factor belongs to a family of polypeptides that are involved in differentiation and cellular proliferation.

METHODS

We examined 30 esophagectomy specimens that were resected for adenocarcinoma (n = 27) and high-grade dysplasia (n = 3). After confirmation of the diagnosis by routine light microscopy, the index lesions (invasive carcinomas) and adjoining Barrett's mucosa were evaluated with a monoclonal antibody against human acidic fibroblast growth factor. The results are expressed with the use of an immunoreactive score that allows distinction between weak, moderate, and strong immunoreactivity.

RESULTS

Adenocarcinoma demonstrated a moderate-to-strong mean immunoreactive score of 8. In contrast, high-grade dysplasia demonstrated a weak-to-moderate mean score of 4.5, which was significantly different (p < 0.05). Intestinal metaplasia and low-grade dysplasia displayed even weaker expression of fibroblast growth factor, with a negligible immunoreactive score less than 1 (p < 0.005). Seventy-five percent of evaluable cases demonstrated an increasing degree of fibroblast growth factor expression in the spectrum of lesions ranging from metaplasia to dysplasia and carcinoma.

CONCLUSIONS

These data indicate that in patients with adenocarcinoma arising in association with Barrett's esophagus, fibroblast growth factor is generally sequentially accumulated in the progression from metaplasia to neoplasia. This progression may affect future investigation into the role of fibroblast growth factors in tumorigenesis and, possibly, the application of fibroblast growth factor immunohistochemistry to diagnosis.