Analysis of immunohistochemical expression of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in gallbladder mucosa: comparative study in acute and chronic calculous cholecystitis.

BACKGROUND: Several studies have shown increased serum levels of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in patients with cholelithiasis. The local expression of the proteins involved in pathogenesis of the disease is poorly recognised. MATERIALS AND METHODS: The authors examined immunohistochemically (IHC) the expression status of IL-1α, IL-6, and TNF-α in gallbladder mucosa of the patients with cholelithiasis as related to acute (ACC) and chronic (CCC) types of cholecystitis. Proinflammatory cytokines were quantitatively evaluated in gallbladder mucosa (epithelium and lamina propria) in ACC (n = 16) and CCC (n = 55) groups using modern spatial visualisation technique. RESULTS: Quantitative analysis of IHC signals showed no significant differences in IL-1α and IL-6, and immunoexpression in patients with ACC and CCC. A significantly greater IHC expression of TNF-α was detected in CCC as compared with ACC group. In either of the patient groups immunoexpression of IL-1α and of TNF-α was significantly higher than that of IL-6. Immunoexpression of TNF-α was significantly higher than that of IL-1α only in CCC group. A positive correlation was disclosed between IHC expression of IL-1α and body mass index in CCC group. IHC expression of TNF-α correlated positively with expression of CD68 molecule (histiocytic marker), number of leukocytes in blood and higher grading of gallbladder wall in ACC group. CONCLUSIONS: A more pronounced IHC expression of TNF-α and IL-1α than IL-6 in both types of cholecystitis may suggest the role of these cytokines in pathogenesis of cholelithiasis. IHC expression of TNF- α shows better correlation with clinical/laboratory data in acute cholecystitis, and its quantitative prevalence over the remaining cytokines points to the role of the TNF-α in maintenance of inflammation in the course of cholelithiasis.

Discordant expression of desmoglein 2 and 3 at the mRNA and protein levels in nodular and superficial basal cell carcinoma revealed by immunohistochemistry and fluorescent in situ hybridization.

BACKGROUND: Basal cell carcinoma (BCC) is the most common human cancer. It is thought that skewed expression of desmogleins (Dsgs) in BCC may promote tumourigenesis. AIM: To comparatively examine expression of Dsg2/Dsg3, using fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in BCC subtypes. METHODS: In total, 84 frozen sections from patients with various clinical or histological subtypes of BCC were analyzed. Expressions of Dsg2/Dsg3 protein and Dsg2/Dsg3 mRNA were evaluated using IHC and FISH, respectively, in BCC nests and BCC-free epidermis, and then quantitatively measured. RESULTS: There was loss of correlation between Dsg2 and Dsg3 (IHC) in nodular and superficial BCC (nBCC, sBCC), and significant correlation between Dsg2 and Dsg3 (FISH) in BCC, but not nBCC and sBCC. CONCLUSIONS: Because more prominent aberrations of Dsg2/Dsg3 expression were seen at the protein than at the mRNA level in BCC, these comparative observations indicate greater importance of events at the proteome level than those at the genome level in tumour functional compartments. Different Dsg2/Dsg3 expression in sBCC and nBCC might corroborate the possibility that sBCC and nBCC are separate conditions. These results may contribute to better understanding of the biological behaviour of BCC.

Expression of phenotypic markers of mast cells, macrophages and dendritic cells in gallbladder mucosa with calculous cholecystitis.

The study aimed at quantitative analysis of expression involving markers of mast cells (tryptase), monocytes/macrophages (CD68 molecule) and dendritic cells (S100 protein) in gallbladder mucosa with acute and chronic calculous cholecystitis. Routinely prepared tissue material from the patients with acute (ACC) (n = 16) and chronic calculous cholecystitis (CCC) (n = 55) was evaluated. Three cellular markers were localized by immunocytochemistry. Their expression was quantified using spatial visualization technique. The expression of tryptase was similar in acute and chronic cholecystitis. CD68 expression in ACC was significantly higher than in the CCC group. Expression of S100 protein was significantly higher in CCC as compared to the ACC group. No significant correlations were disclosed between expression of studied markers and grading in the gallbladder wall. A weak negative correlation was noted between expression of CD68 and number of gallstones in the CCC group. The spatial visualization technique allowed for a credible quantitative evaluation of expression involving markers of mast cells (MCs), monocytes/macrophages (Mo/Ma) and dendritic cells (DCs) in gallbladder mucosa with ACC and CCC. For the first time mucosal expression of S100 protein-positive DCs was evaluated in calculous cholecystitis. The results point to distinct functions of studied cell types in the non-specific immune response in calculous cholecystitis.