Cell cycle regulation in patients with intestinal metaplasia at the gastro-oesophageal junction.
OBJECTIVE
The incidence of oesophageal adenocarcinoma is increasing rapidly and this may be related to the presence of intestinal metaplasia (IM) at the gastro-oesophageal junction (GOJ). Recent studies have distinguished two subtypes of IM at the GOJ: short segment Barrett's oesophagus (SSBO) and IM at a normal squamo-columnar junction (IMNSCJ). Because abnormal expression of cell cycle regulators is common in cancer and precancerous states, cell cycle regulation was studied in patients with IM at the GOJ.


METHODS
Biopsy samples and resected materials were identified from patients with SSBO (10), IMNSCJ (14), a normal SCJ with (14) and without (12) inflammation, conventional Barrett's oesophagus (BO) (12), and oesophageal adenocarcinoma (12). Sections were stained with antibodies to p21, p27, p53, Ki67, cyclin D1, and c-erbB2 and were assessed independently by two observers, using predetermined criteria.


RESULTS
Patients with oesophageal adenocarcinoma showed high expression of c-erbB2, p53, p27, and Ki67. Patients with BO showed expression of c-erbB2 but little expression of other markers. Greatly increased expression of cyclin D1 was seen in patients with IMNSCJ. The expression of all other markers was similar in patients with IMNSCJ and those with SSBO. Cyclin D1 and c-erbB-2 were coexpressed in patients with SSBO and IMNSCJ, and their expression was associated with the presence of p53 and p21.


CONCLUSIONS
Although the proposed aetiologies of SSBO (gastro-oesophageal reflux) and IMNSCJ (Helicobacter pylori infection) differ, the cell cycle response is similar and both may have malignant potential.
Trudgill
N J
NJ
Department of Gastroenterology, Northern General Hospital, Sheffield S5 7AU, UK.
Suvarna
S K
SK
Royds
J A
JA
Riley
S A
SA
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000032:analysis*; D019938:Cyclin D1 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008679:Metaplasia; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D009124:Muscle Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D015415:Biomarkers; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human; C058992:Tagln protein, mouse