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Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighted the hepatocytic vitronectin expression as the most promising specific biomarker for iron-associated fibrogenesis in HCV infections. Next, the robustness of our in vitro findings was challenged in human liver biopsies by immunohistochemistry and yielded two major results: (i) hepatocytic vitronectin expression is associated to liver fibrogenesis in HCV-infected patients with iron overload; (ii) hepatic vitronectin expression was found to discriminate also the transition between mild to moderate fibrosis in HCV-infected patients without iron overload., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Human papillomavirus (HPV) has been identified as the major cause of cervical cancer worldwide and HPV DNA testing is recommended in primary cervical cancer screening. Several molecular tests for detection/typing of HPV DNA with different sensitivity and specificity are commercially available. The present study compared the performance of the Abbott RealTime High Risk HPV assay and the Genomica HPV Clinical Array CLART2 in 78 specimens (63 cervical smears and 15 rectal/urethral swabs).The typing results of the Genomica assay were in absolute agreement with each of the four possible result categories of the Abbott assay (HPV16, HPV18, Other HR HPV, not detected) in 87.2% (68/78) of the samples, with a Cohen' kappa agreement coefficient for every HR type of 0.62 (95% CI: 0.39-0.85), higher in cervical swabs (k = 0.74, 95% CI: 0.50-0.99) than in rectal/urethral swabs (k = 0.36, 95% CI: 0.00-0.82). There was an excellent agreement of the Genomica results with those of Abbott in cervical samples harbored HPV single infection (100% agreement). Nonetheless, both methods may lose sensitivity for detecting HPV types in multiple infections, giving discordant results (10/78). This underlines the importance of establishing the analytical sensitivity in HPV type detection in single and multiple HPV infections. In rectal/urethral swabs, 5 of 15 (33%) discordant cases were observed, most of which became compatible when the Genomica assay was performed starting from nucleic acid extracted with the Abbott m2000sp system. These results suggest that nucleic extraction based on the magnetic beads technique is suitable for HPV DNA detection in urethral/rectal swabs., (© 2013 The Authors APMIS © 2013 APMIS.)

Schwannoma is a well-described, benign nerve sheath tumor of the soft tissue, but is rare in the gastrointestinal tract. Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions. In this report, we describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts. Immunohistochemical analysis revealed strong and diffuse positivity for the S-100 protein. To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes, it is better to use the designation "mucosal Schwann hamartoma".

We report a case of drug-related toxicity after liver transplantation for hepatocellular carcinoma in a HIV-HCV co-infected patient. Before transplant the patient was on a triple antiretroviral therapy (zidovudine and lamivudine and efavirenz) with a stable CD4+ cell count >500 cells/microL. Liver transplantation was performed with a liver graft showing a 10% of macrosteatosis and with a graft-to-recipient body weight ratio of 1.3. Immunosuppression was achieved with tacrolimus, azathioprine and steroids. The antiretroviral therapy was resumed in the first postoperative day as the early graft function was in the normal range. After a few hours the patient showed myoglobinuria, rhabdomyolysis and a fast-deteriorating graft function. All drugs were withdrawn except steroids and an empiric therapy with riboflavin and glutathione was maintained for five days until myoglobinuria ended. Nevertheless the serum levels of tacrolimus remained in the therapeutic range for six days when it was reintroduced at a reduced dosage (0.01 mg/kg/die). The postoperative course was complicated by tense ascites and severe hyperbilirubinemia without any rejection episodes. The patient was discharged 48 days post-transplantation with a good liver function. During the following year no signs of aggressive HCV-HIV recurrences were observed and the patient is maintaining a CD4+ cells count >400 without antiretroviral therapy.

A computer-assisted assay based on the quantitative analysis of DNA methylation in individual interphase nuclei by indirect immunolabelling with anti-5-methylcytosine antibodies was recently developed in our laboratory. In situ analyses were performed on individual nuclei from normal and experimentally hypo- or hypermethylated cultured cells as well as on human peripheral blood B-lymphocytes from normal and chronic lymphoid leukemia (CLL) samples. We present the results obtained on cells from patients affected by different degrees of preneoplastic or neoplastic changes of the uterine cervix as compared to normal controls. The analysis of DNA methylation in individual cells from cytofuge samples was performed as follows: within each nucleus the eu- and heterochromatin methylation levels were quantified in the grey scale range by dedicated software in terms of numbers, areas and optical densities (ODs) of the immunolabeled dense heterochromatic regions ("spots"), and of the optical density of nuclear background, i.e., of nuclear euchromatin. Analogously, in randomly chosen microscope fields of tissue sections from paraffin-embedded samples, progressive tissue demethylation was observed in dysplastic and cancer cells as compared to normal ones. Both methods showed significant and progressive DNA hypomethylation in dysplastic and cancer cells as compared to control specimens.

Unlabelled: The purpose of this study was to clarify the role and the predictive strength of the adhesion molecule CD44s (standard isoform) in colorectal carcinogenesis., Materials and Methods: CD44s immunohistochemical expression was evaluated in 100 patients with colon adenoma and 100 patients with colon adenocarcinoma and adjacent non-neoplastic mucosa (ANNM). The patients were followed-up for five years., Results: CD44s immunoreactivity was expressed in low-moderate-high-grade dysplasia adenomas and associated with adenocarcinoma (p = 0.01), ANNM (p = 0.05) and pTNM stage (p = 0.00001). Univariate analysis revealed that CD44s expression was associated with overall survival (OS) in carcinomas (p = 0.01) and ANNM (p = 0.05). Bivariate analysis revealed that CD44s was associated with OS in stages I and II patients (p = 0.03). Multivariate analysis revealed that stage (p = 0.0001) and CD44s expression (p = 0.05) were independent predictors of OS., Conclusion: CD44s is involved in colon carcinogenesis and is associated with aggressive carcinomas. The immunohistochemical expression of CD44s may reveal cells that have lost their adhesion ability and therefore detect carcinomas with high metastatic power.