Decreased and aberrant nuclear lamin expression in gastrointestinal tract neoplasms.

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.

Regional distribution in human of a novel aortic collagen-associated microfibrillar protein.

We have reported two hypothetical proteins of human aorta, based on sequences cloned from a cDNA library constructed from mRNAs purified from the adventitia. These sequences have immunoglobulin-kappa (IgK)-like domains, and we have shown that microfibrils of the aortic adventia are immunoreactive with antibodies against IgK. The present study was performed to characterize more specifically the regional distribution in human of one of these proteins in particular and the distribution of matrix proteins with IgK-like motifs in general. An antibody was raised in rabbit against a synthetic peptide based on a unique sequence in one of the hypothetical proteins (NPSNRVTPQKNFP), which has not been reported in the sequence of any other known protein. This antibody and a rabbit anti-human IgK antibody were used as first antibodies in the staining reactions. A monoclonal mouse anti-smooth muscle cell alpha-actin antibody was also used. Immunoreactivity with the sequence-specific antibody was limited to the aorta and large vessels. Adventitial microfibrillar staining was more conspicuous in the abdominal aorta than in the thoracic aorta and in the internal iliac than in the external iliac artery. The immunoreactive protein was associated with fibroblasts and not smooth muscle cells. Immunoreactivity coated the collagen fibers diffusely, while elastin fibers were not stained. Further studies using antibodies against IgK demonstrated immunoreactivity of collagen and fibroblasts in a variety of tissues: spleen, ovary, testicle, cervix, prostate, skin, and breast (but not brain). Immunoglobulin motifs may be a feature of matrix proteins produced by fibroblasts in many tissues, but the first motif that we identified from a cDNA library of aortic adventitia appears to be specific to aorta and large vessels.

Immunoreactivity of adventitial matrix fibrils of normal and aneurysmal abdominal aorta with antibodies against vitronectin and fibrinogen.

PURPOSE: We have reported that immunoglobulin G (IgG) harvested from specimens of aneurysmal abdominal aorta (AAA) is immunoreactive with a fibrillar component of the matrix of the aortic adventitia. In further studies we have reported the partial amino acid sequence of a 40-kDa protein, purified from the adventitia of the human aorta, which we have called aortic aneurysm antigenic protein-40 kDa (AAAP-40). AAAP-40 has homologies with bovine microfibril-associated glycoprotein-36 kDa (MAGP-36). Both AAAP-40 and MAGP-36 have homologies to fibrinogen beta (FB-b) and vitronectin (VN). The purposes of the present experiments were (1) to determine whether antibodies against VN and fibrinogen are immunoreactive with elements of the normal and/or aneurysmal aortic wall, and (2) to determine whether these antibodies are immunoreactive with soluble extracts of aortic proteins. METHODS: Paraffin-embedded tissue sections of normal and aneurysmal aorta were probed with polyclonal rabbit antihuman VN and antihuman FB-b antibodies. Immunoblots of soluble aortic proteins were evaluated with the same antibodies. Histochemical preparations with Gomori's aldehyde fuchsin and elastin-von-Gieson solutions were also performed. RESULTS: Anti-VN and FB-b antibodies reacted with matrix fibrils in the aortic adventitia in both normal and aneurysmal specimens, with a distribution that resembles the appearance of fibrils that are stained by Gomori's reaction. By comparison to normal adventitial fibrils, fibrils in the specimens from AAA appeared fragmented, coiled, and frayed. Antibodies against VN and FB-b were immunoreactive in immunoblots with a soluble aortic protein of molecular weight approximately 40 kDa, consistent with the migration of AAAP-40. CONCLUSIONS: There appear to be immunodeterminants in AAAP-40 that are recognized by polyclonal antibodies against VN and FB-b.

Elastin degradation products induce adventitial angiogenesis in the Anidjar/Dobrin rat aneurysm model.

BACKGROUND: Infusion of the abdominal aorta with pancreatic elastase induces aneurysms in a rat model (Anidjar/Dobrin). Because elastolysis liberates elastin degradation products (EDPs), the present experiment was carried out to test the hypothesis that an EDP alone could induce features of aneurysm disease. METHODS: The EDP val/gly/val/ala/pro/gly (VGVAPG), elastase, or saline solution was infused into infrarenal aorta (n = 4/group). After 1 week aortic diameters were measured, and the tissues were prepared for histologic examination. Adventitial capillaries (vessels per high-power field) were counted over a standardized preparation of aorta. Wall thickness was measured by means of computer-aided planimetry. RESULTS: There was an increase of greater than 100-fold in mean vessels per high-power field in aortas receiving VGVAPG or elastase versus saline controls (4.10 +/- 0.68 SEM or 4.48 +/- 0.49 SEM versus 0.03 +/- 0.03 SEM, respectively, p < 0.05). The VGVAPG-perfused group had a 26% +/- 4% SEM increase in diameter from baseline that was statistically significant (p < 0.01), but the aortas did not reach aneurysmal dimensions. CONCLUSIONS: Although no aneurysms occurred at 1 week after the infusion of EDP, the results demonstrate that the EDP VGVAPG can induce a characteristic feature of aneurysm disease. The model permits study of the earliest stages of experimental aneurysm formation and raises interesting questions regarding the role of the vasa vasorum in this pathologic process.

Enteropathy associated with the acquired immunodeficiency syndrome.

To explore the effect of the acquired immunodeficiency syndrome on gastrointestinal structure and absorption, the cases of 12 homosexual men with the syndrome and 11 homosexual controls were studied. Seven patients had diarrhea with weight loss. Bacterial or parasitic infections were not detected. All patients were malnourished; had significantly fewer T-lymphocyte helper and suppressor cells; and had significantly lower body weights, midarm circumferences, serum albumin concentrations, and iron binding capacities than homosexual controls. D-Xylose malabsorption and steatorrhea were present in patients, especially those with diarrhea. Jejunal and rectal biopsy samples were histologically abnormal in all patients with diarrhea. Jejunal abnormalities included partial villus atrophy with crypt hyperplasia and increased numbers of intraepithelial lymphocytes. Rectal abnormalities included intranuclear viral inclusions, mast cell infiltration in the lamina propria, and focal cell degeneration near the crypt base. The histologic findings suggest that a specific pathologic process occurs in the lamina propria of the small intestine and colon in some patients with the syndrome.

Malignant fibrous histiocytoma of spermatic cord.

Malignant fibrous histiocytomas are very rare, particularly those related to urogenital organs. We report herein the third known case of this entity involving the spermatic cord. Summary of the previously reported 2 cases is given with recent follow-up. Prognosis is poor.

Survival of patients with unsuspected prostatic carcinoma after open prostatectomy.

This study is concerned with the clinicopathologic findings in 40 patients with unsuspected carcinoma of the prostate found at the time of open prostatectomy and the correlation of these findings with survival. There is a significant correlation between pathologic findings and clinical outcome.