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Background-Altered expression of lamins A/C and B1, constituent proteins of the nuclear lamina, may occur during diVerentiation and has also been reported in primary lung cancer. Aims-To examine the expression of these proteins in gastrointestinal neoplasms. Patients-Archival human paraYn wax blocks and frozen tissue from patients undergoing surgical resection or endoscopic biopsy. Methods-Immunohistochemistry and western blotting using polyclonal antisera against A type lamins and lamin B1. Results-The expression of lamin A/C was reduced and was frequently undetectable by immunohistochemistry in all primary colon carcinomas and adenomas, and in 7/8 primary gastric cancers. Lamin B1 expression was reduced in all colon cancers, 16/18 colonic adenomas, and 6/8 gastric cancers. Aberrant, cytoplasmic labelling with both antibodies occurred in some colonic cancers and around one third of colonic adenomas. Cytoplasmic lamin A/C expression was detected in 3/8 gastric cancers. Lamin expression was reduced in gastric dysplasia, but not intestinal metaplasia, atrophy, or chronic gastritis. Lamin expression was low in carcinomas of oesophagus, prostate, breast, and uterus, but not pancreas. Conclusions-Reduced expression of nuclear lamins, sometimes together with aberrant, cytoplasmic immunoreactivity is common in gastrointestinal neoplasms. Altered lamin expression may be a biomarker of malignancy in the gastrointestinal tract. (Gut 1999;45:723-729)