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 differentiation and has also been reported in primary lung cancer.

Aims: To examine the expression of these proteins in gastrointestinal neoplasms.

Patients: Archival human paraffin 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.

Figure 1

Normal colonic crypt immunostained for lamin A/C (A) and lamin B1 (B) showing dark nuclear membrane staining in both epithelial cells and lamina propria cells. Lamin A/C is most highly expressed in cells in the upper crypt. Original magnification × 400.

Figure 2

Expression of lamins in colon neoplasms. There is absent nuclear immunoreactivity with antibodies against lamin A/C (A) and B1 (B), and cytoplasmic labelling of lamin A/C (A) and B1 (B) in the gland of an adenomatous colonic polyp. In a colonic adenocarcinoma, lamin A/C is absent (C) and lamin B1 notably reduced (D). Original magnification × 400. The cytoplasmic immunolabelling of lamin A/C (E) and lamin B1 (F) between the nucleus and apical pole of adenomatous epithelial cells is better appreciated at higher magnification (× 1000).

Figure 3

Representative immunoblot of normal (N) and cancer (C) tissue pairs from three patients with primary colorectal carcinoma. No consistent differences in the expression of lamin A/C or B1 were found in these tissue lysates. Migration of molecular mass standards in kilodaltons is shown on the right.

Figure 4

Expression of nuclear lamins in gastric tissue. In the non-neoplastic mucosa from a gastrectomy specimen removed for cancer, strong expression of nuclear lamin A/C (A) and B1 (B) is evident throughout, including both the relatively normal mucosa on the left and in the area of intestinal metaplasia, on the right. There is notably reduced expression of lamin A/C (C) and B1 (D) in an intestinal type gastric cancer. Original magnification × 400.