Allelic loss involving the tumor suppressor genes APC and MCC and expression of the APC protein in the development of dysplasia and carcinoma in Barrett esophagus

Samples of Barrett metaplastic specialized epithelium (SE), low-grade dyspl asia (LGD), high-grade dysplasia (HGD), and invasive adenocarcinoma (CA) de rived from 36 esophagectomy specimens were studied for loss of heterozygosi ty (LOH) in APC and MCC and for expression of APC protein. Of 18 cases that were heterozygous (informative)for APC, LOH was found in none of 14 SE sam ples, 2 of 8 LGD samples, 3 of 11 HGD samples, and 5 of 17 CA samples. Immu nohistochemically, markedly reduced expression of APC protein. (<50% positi ve cells) Ir as found in 3 of 19 HGD samples and 4 of 35 CA samples but not in SE or LGD samples. Of 17 cases informative for the MCC gene, LOH was de tectable in I of 14 SE samples, none of 7 LGD samples, none of 9 HGD sample s, and 4 of 16 CA samples. Allelic loss of APC and/or loss of APC protein expression occurs earlier in the metaplasia-dysplasia-carcinoma sequence in Barrett esophagus than LOH in the MCC gene. The determination of alterations at APC or MCC would be of limited importance for the surveillance of patients with Barrett esophagus .