Disorganisation of intermediate filament structure in alcoholic and other liver diseases.

The distribution of Mallory body antigens JMB1 and 2 was examined in 82 human fresh diagnostic needle liver biopsies and 28 necropsies by the indirect immunoperoxidase technique using 2 monoclonal antibodies (anti-JMB1 and 2) against Mallory bodies. The JMB1 antigen was detectable in bile duct epithelium and in hepatocytes of histologically normal livers. It was also found in all Mallory bodies in various hepatic disorders. This antigen was markedly increased in the cytoplasm of all liver cells in acute alcoholic hepatitis superimposed on alcoholic cirrhosis, in most cases of acute alcoholic hepatitis, and in severe fatty infiltration of the liver with or without Mallory body formation. Mallory bodies contained this antigen but the cytoplasm of Mallory body containing cells lacked JMB1. In normal liver the JMB2 antigen was localised on the cytoplasmic intermediate filament network of hepatocytes and bile duct epithelium; and almost all Mallory bodies also contained this antigen but the adjacent cytoplasm of these cells lacked JMB2. In severe alcoholic liver disease these antigens could not be detected in large zones of hepatocytes even when these hepatocytes did not contain Mallory bodies. It is evident that there is disorganisation of intermediate filament constituents in severe alcoholic liver disease.     

Serum interleukin-6 is elevated in symptomatic carotid bifurcation disease

Introduction – The levels of circulating proinflammatory cytokines may express the extent of the inflammatory response and their participation in plaque progression and rupture needs to be evaluated. We aimed to investigate differences in circulating levels of proinflammatory cytokines and in plaque infiltration by macrophages between patients undergoing carotid endarterectomy for symptomatic and asymptomatic carotid atherosclerotic disease. Methods – One hundred nineteen patients (91 men and 28 women; mean age 66 ± 8 years; range 42–83 years) who underwent carotid endarterectomy for significant (>70%) carotid bifurcation stenosis were enrolled in this study. Patients were characterized as symptomatic (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), IL‐1β, serum amyloid A (SAA), and high‐sensitivity C‐reactive protein (hs‐CRP) were evaluated. Macrophage infiltration of the plaque was assessed quantitatively from endarterectomy specimens using the monoclonal antibody CD68. Results – Serum IL‐6 levels were significantly higher in patients with symptomatic compared with those with asymptomatic carotid disease (3.3 [2.0–6.5] pg/ml vs 2.5 [1.9–4.1] pg/ml, P = 0.02). TNF‐α, IL‐1β, SAA, and hs‐CRP levels did not differ significantly between the two groups. Symptomatic patients had also more intense macrophage accumulation in the carotid plaque compared with asymptomatic patients (0.6 ± 0.1% vs 0.4 ± 0.1%, P < 0.001). Although there were correlations between the levels of the different inflammatory markers, there were no correlation between any of them and the extent of plaque macrophage infiltration. Conclusion – Patients with symptomatic carotid atherosclerotic disease have elevated serum IL‐6 levels compared with asymptomatic patients. Symptomatic patients have also more intense macrophage infiltration of the atherosclerotic plaque suggesting that inflammatory process may contribute to the destabilization of the carotid plaque.     

Immunohistochemical detection of the expression of the cell adhesion molecules E-cadherin, desmoglein-2, beta4-integrin, ICAM-1 and HCAM (CD44s) in Warthin's tumour of the parotid gland

The study of the expression of cell adhesion molecules (CAMs), E-cadherin, desmoglein-2, beta4-integrin, HCAM (CD44s) and ICAM-1 in Warthin's tumours. Twenty formalin--fixed, paraffin--embedded parotid Warthin's tumours were studied using an Envision/HRP immunohistochemical technique. Beta4-integrin was strongly expressed in all cell-basement membrane and intercellular contacts of the epithelium, E-cadherin and desmoglein-2 in cell-cell contacts, but not in basal cell-basement membrane connections and on columnar cells' luminal surfaces, HCAM (CD44s) in intercellular contacts of both luminal (mainly), basal cells and also in the periphery of monocytic-lymphocytic stroma, and ICAM-1 was weak to moderate expressed in both luminal and basal epithelial cells and strongly in the germinal lymphocytic centres. CAM expression suggests a bilayered excretory ductal structure of the neoplastic epithelium in Warthin's tumour, as a result of hyperplastic process of the glandular epithelium that interacts with the excessive lymphoid tissue of the stroma.     

Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis

Our aim was to study the effect of lower airway infection on clinical parameters, pulmonary function tests, and inflammation in clinically stable infants and young children with cystic fibrosis (CF). To accomplish this goal, a prospective cohort of screened CF patients under 4 years of age were studied, using elective anesthesia and intubation for: passive respiratory mechanics (single breath occlusion passive deflation) and lung volumes (nitrogen washout), under neuromuscular blockade; and bronchoalveolar lavage (BAL) of 3 main bronchi for cytology, cytokine interleukin (IL)-8, and quantitative microbiology. There were 22 children studied, with a mean age of 23.2 months (6.7-44 months). A greater relative risk of lower airway pathogens was associated with prior respiratory admission (3.60, 95% confidence interval [CI] 2.87-4.51), history of asthma (1.75, 95% CI 1.52-2.03), and chronic symptoms (1.50, 95% CI 1.23-1.83), especially wheeze (1.88, 95% CI 1.61-2.19). Lower respiratory pathogens (> or = 10 cfu/ml BAL) were found in 14 out of 22, and greater than 10(5) cfu/ml in 8 out of 22 subjects. The level of pathogens in BAL (log10 cfu/ml) explained 78% of the variability in percent neutrophils and 34% of the variability in IL-8 levels. Pathogen level also correlated with pulmonary function tests of specific respiratory system compliance (r -0.49, p = 0.02) and functional residual capacity over total lung capacity (r 0.49, p = 0.03). We conclude that the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance, and degree of air trapping.     

Human papilloma virus (HPV) is possibly involved in laryngeal but not in lung carcinogenesis

Data on human papilloma virus (HPV) involvement in preneoplastic and neoplastic lesions of the larynx and lung are limited and conflicting. The presence of HPV was investigated in a series of laryngeal specimens and non-small cell lung carcinomas (NSCLCs). The laryngeal samples (154) comprised 14 cases with hyperplasia without dysplasia, 49 with dysplasia, and 91 squamous cell carcinomas (SqCCs). The NSCLCs included 31 SqCCs, 32 adenocarcinomas, and 5 undifferentiated large cell carcinomas. Furthermore, we examined, for HPV DNA sequences, 14 bronchial metaplastic squamous lesions located next to cancerous areas. We used a sensitive nested polymerase chain reaction assay (NPCR), dot blotting, and in situ hybridization. The findings were correlated with clinicopathologic features of the patients. In the laryngeal specimens, NPCR analysis showed HPV DNA in 20 (13%) of the 154 specimens. Notably, 19 of 20 HPV-positive cases were carcinomas and only one was a mild dysplastic lesion. Typing of the carcinomas showed single HPV 6, 16, 18, and 33 infection in 1 (1.1%), 12 (13.2%), 2 (2.2%), and 1 (1.1%) samples, respectively, and HPV 6/33, 16/33, and 6/18 coinfection in three carcinomas. In situ hybridization findings were in agreement with PCR results, with the exception of two cases in which HPV 18 DNA was detected only by PCR. HPV was more frequently observed in heavy smokers than in patients with low daily cigarette consumption and nonsmokers (P = .03). There was no correlation between virus infection and gender, grade, and lymph node status of the carcinomas. None of the NSCLCs or adjacent metaplastic squamous epithelium contained HPV DNA sequences. The presented data suggest a contributory role of HPV in late stages of laryngeal carcinogenesis, because all premalignant lesions were negative but one. This study does not support a potential role of HPV in the development of NSCLCs.     

p53 Overexpression in laryngeal squamous cell carcinoma and dysplasia

Aim—To investigate the expression of p53 protein in invasive squamous cell carcinoma (SCC) of the larynx and dysplasia in relation to histological grade and tobacco smoking.     

Intra-abdominal desmoplastic small-cell tumours with divergent differentiation. Report of two cases and review of the literature.

Two intraabdominal desmoplastic small cell tumours presenting in young adult males and involving the entire peritoneum, with no evident single primary site, have been studied. The histological pattern was suggestive of a metastatic small cell epithelial neoplasm, but immunohistochemical study revealed strong reactivity for cytokeratins, vimentin and desmin indicating synchronous epithelial and myogenous differentiation. In addition epithelial membrane antigen and neuron specific enolase were also positive. Electron microscopy showed fairly undifferentiated tumour cells with striking desmosome-like junctions, containing prominent paranuclear whorls of intermediate filaments, and a typical myofibroblastic stroma around neoplastic islands. Although the histogenesis of these recently described and rare tumours still remains uncertain, it seems that they constitute a reproducible entity which requires differential diagnosis from other small cell tumours of childhood and young adulthood.     

Can p53 nuclear over-expression, Bcl-2 accumulation and PCNA status be of prognostic significance in high-risk superficial and invasive bladder tumours?

AIMS: To evaluate p53 and Bcl-2 expression and proliferating status (PCNA) in subgroups of patients with high-risk superficial and invasive bladder cancer, with relation to cancer progression and death, and to correlate the results with established clinical prognostic factors. METHODS: Paraffin-embedded sections from 42 high-risk superficial (T1G2,T1G3) and 33 invasive (T2-T4aG3 N0M0) tumours were investigated immunohistochemically for p53, Bcl-2 and PCNA. The median follow-up was 52 months. RESULTS: In the cohort of superficial tumours, statistical analysis showed that p53 and PCNA positivity were significant prognostic factors (P-values: 0.008 and 0.006, respectively) for disease-specific death (DSD). When life expectancy was evaluated (log-rank test), p53(+) (P = 0.015) and PCNA(+) (P = 0.017) offered the most accurate prognosis compared to grade, tumour size and multiplicity. Bcl-2 status had no significant effect on patient survival. In the subset of muscle-invasive tumours we failed to demonstrate any important role of p53, Bcl-2 or PCNA positivity. CONCLUSIONS: p53 and PCNA over-expression may offer valuable additional prognostic information in high-risk subgroups of superficial bladder tumours. From our results, Bcl-2 does not appear to contribute significantly to the prognosis of these patients. None of the studied markers offered prognostic information in muscle-invading disease.     

Metastatic renal clear cell carcinoma in the parotid gland: A study of immunohistochemical profile and cell adhesion molecules (CAMs) expression in two cases

Metastasis of renal cell carcinoma (RCC) may involve any organ, including the parotid salivary gland. While the definition of salivary gland neoplasms with clear cell transformation can be concluded by the synchronous presence of areas showing typical morphology, sometimes the definition of a metastatic RCC in the parotid is difficult and the application of immunohistochemistry may support the clinical and radiographic observations in the final diagnosis. The aim of this paper was to describe the heterogeneous immunohistochemical features and, furthermore, to characterize the pattern of expression of cell adhesion molecules (CAMs) E-cadherin, β4-integrin, desmoglein-2, ICAM-1 and CD44s (HCAM) in two cases of metastatic parotid RCC.