Decreased and aberrant nuclear lamin expression in gastrointestinal tract neoplasms

Abstract

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)

Nuclear lamins: key regulators of nuclear structure and activities

“…An additional study evaluating only three tissue samples has found reduced expression of lamins A, C and B1 in the non-SCLC tissue samples [185]. (17 of 17) of primary colon adenocarcinomas, and in 7 of 8 primary gastric adenocarcinoma specimens [185]. Lamin B1 expression was reduced in all the 17 colonic specimens and in 6 of 8 of the gastric specimens.…”

“…The first study used immunohistochemistry techniques and found reduced expression of lamins A, C and B1 in three out of four patients with prostatic cancer [185]. The other study used immunoblot assays and reported 37 prostatic cancer patients with a significant increase in lamin B1 and no significant change in lamins A and C [193].…”

“…[183,184] [184] (Table 1). An additional study evaluating only three tissue samples has found reduced expression of lamins A, C and B1 in the non-SCLC tissue samples [185]. (17 of 17) of primary colon adenocarcinomas, and in 7 of 8 primary gastric adenocarcinoma specimens [185].…”

“…In a small cohort of patients with oesophageal squamous and adenocarcinoma there was reduced expression of both lamins A and C and B1 [185] (Table 2) [185,188] (Table 2). …”

The role of Lamin A in cytoskeleton organization in colorectal cancer cells

“…There is no overall pattern of A-type lamin expression in cancers and frequently inconsistent patterns are observed between cancer subtypes. Many studies show lamin A/C to be downregulated in tumour cells, [2][3][4] but others show positive or upregulated expression. 2,5,6 Sometimes expression levels can vary dramatically even within cancer subtypes; for example, in colorectal and basal cell carcinomas, A-type lamin expression can be positive, 4,5,7 reduced 3,4 or negative 3,4,7 in tumour tissue.…”