Diagnostic Value of Claudin-4 and EZH2 Immunohistochemistry in Effusion Cytology.

BACKGROUND: Metastatic adenocarcinoma (MAC) accounts for most cases of malignant effusions. Sometimes, it can be difficult to distinguish MAC from reactive mesothelial cells (RMC) in cytologic specimens. Our aim was to assess the diagnostic performance of a novel immunohistochemical panel composed of claudin-4 and EZH2 in differentiating MAC from RMC in effusion cytology. METHODS: A total of 80 cases of serous effusions (48 MAC and 32 RMC) were included. Immunohistochemistry using claudin-4 and EZH2 was performed on cell block sections of these cases. Assessment of staining patterns, intensity and percentage of target cells stained was done. RESULTS: Claudin-4 showed membranous staining in 46/48 of MAC and 1/32 of RMC. High EZH2 (≥ 50% of target cells) was detected in 42/48 MAC and 2/32 RMC. For the discrimination between MAC and RMC, claudin-4 exhibited 95.8% sensitivity and 96.9% specificity, high-EZH2 exhibited 87.5% sensitivity and 93.8% specificity, while the combination of both claudin-4 and high EZH2 showed 100% sensitivity and 90.6% specificity. CONCLUSION: Claudin-4 shows high sensitivity and specificity in differentiation between MAC and RMC in effusion cytology, and might be useful as a solitary marker for MAC. Adding EZH2 to claudin-4 increases the sensitivity to 100%. However, the interpretation of EZH2 results can be challenging due to its focal expression in RMC and inflammatory cells.

The potential relationship between gasotransmitters and oxidative stress, inflammation and apoptosis in lead-induced hepatotoxicity in rats.

The interrelationship between gasotransmitters and oxidative stress, inflammation and apoptosis in lead-induced hepatotoxicity was investigated in this study. On prolonged exposure, lead was accumulated in liver tissue of rats and impaired liver function and structure as assessed by measurement of the serum hepatic function markers and by histopathological examination. The accumulated metal induced oxidative stress, inflammation and apoptosis in the liver. Also, it increased nitric oxide (NO) production and decreased hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in liver tissue. Decreasing of NO production by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and carbon monoxide (CO) level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of liver function and structure. Concomitantly, these agents inhibited lead intoxication-induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of HO-1 concentration and H2S level. Furthermore, concurrent treatment with these agents inhibited lead intoxication-induced increase in the protein expressions of inducible NO synthase, tumor necrosis factor-alpha, interleukin-1beta and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine-γ-lyase in the liver. NO donor, l-arginine and H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively aggravated the toxic effects of lead. These results indicate, for the first time, that there is an interrelationship between gasotransmitters and lead-induced hepatotoxicity. The ability of L-N AME, NaHS and CORM-A1 to provide protective effects against lead-induced hepatotoxicity may positively correlate, to their ability to suppress hepatic oxidative stress, nitrosative stress, inflammation and apoptosis.

Do BRAFV600E mutation and sodium-iodide symporter expression affect the response to radioactive iodine therapy in patients with papillary thyroid carcinoma?

OBJECTIVE: To report on the associations between BRAF and sodium iodide symporter expressions and treatment outcomes in patients with papillary thyroid carcinoma. METHODS: Inclusion criteria included a pathologic diagnosis of papillary thyroid carcinoma of any stage, thyroidectomy followed by radioactive iodine therapy, and follow-up for at least 12 months after initial therapy. Events were classified as persistent or recurrent disease based on a clinical or investigational evidence of disease within or after, respectively, 1 year from initial therapy. Disease-free survival was calculated between the dates of surgery and confirmed event. Patients with no evidence of disease were censored at their last follow-up (censored group). BRAF mutation and sodium-iodide symporter expressions were evaluated using immunohistochemistry. RESULTS: The study included 78 patients (60 females, 18 males) with median age 36 years (range: 20-70 years). BRAF was positive in 78%, equivocal in 13%, and negative in 9%. Sodium-iodide symporter was positive in 88%. BRAF mutation was significantly associated with increasing tumor size, presence of lymphovascular invasion, classic subtype of papillary thyroid carcinoma, thyroid capsular infiltration, and lymph node metastasis. Sodium-iodide symporter expression was not associated with any clinical or pathologic characteristics. Patients with negative or equivocal BRAF had significantly better disease-free survival (82%, 3 events) compared to the positive group (41%, 33 events; P=0.02). CONCLUSION: In patients with papillary thyroid carcinoma, BRAF mutation is associated with high-risk pathological characteristics and worsened disease-free survival.

The interrelationship between gasotransmitters and lead-induced renal toxicity in rats.

This study explored the role of gasotransmitters in lead-induced nephrotoxicity. Long-term exposure of rats to lead resulted in its accumulation in kidney. The accumulated metal impaired kidney function and structure. Lead intoxication resulted in oxidative stress, inflammation and apoptosis in kidney. In addition, it resulted in nitric oxide (NO) overproduction and decrease in hydrogen sulfide (H2S) level and heme oxygenase (HO-1) concentration in kidney. Inhibition of NO overproduction by L-N(G)-nitroarginine methyl ester (L-NAME) and increasing of H2S level by sodium hydrosulfide (NaHS) and CO level by carbon monoxide-releasing molecule-A1 (CORM-A1) inhibited lead-induced impairment of kidney function and structure. These agents inhibited lead-intoxication induced oxidative stress, inflammation, apoptosis, nitrosative stress and reduction of H2S level and HO-1 concentration. Also, concomitant treatment with these agents inhibited lead intoxication-induced increase in protein expressions of inducible NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß) and caspase-3 as well as decrease in protein expressions of HO-1 and cystathionine- γ-lyase (CSE) in kidney. The NO donor, L-arginine and the H2S and CO biosynthesis inhibitors, trifluoro-DL-alanine and zinc deutroporphyrin, respectively produced opposite effects and aggravated the toxic effects of lead. These results demonstrate, for the first time, that gasotransmitters play an important role in lead-induced nephrotoxicity.

Expression of galectin-1 and galectin-3 in renal cell carcinoma; immunohistochemical study.

BACKGROUND AND AIMS: Galectins comprise a large family of calcium independent lectins. Galectin-1 and galectin-3 contribute to neoplastic transformation, angiogenesis, and tumor metastasis in some cancers. This study aimed at studying the immunohistochemical expression of both galectin-1 and galectin-3 in renal cell carcinoma (RCC) variants and detecting the possible association of galectins with various clinicopathological parameters. MATERIALS AND METHODS: Sections from 67 formalin-fixed paraffin-embedded tissue blocks of RCC variants were stained with galectin-1 and galectin-3. Expression was assessed in tumor tissue and adjacent renal parenchyma and was correlated with clinicopathological criteria. RESULTS: In apparently normal renal parenchyma adjacent to tumor tissue, galectin-1 was expressed in 27 (40.2%) of specimens in renal tubules and glomeruli, while 34 (50.7%) of specimens showed galectin-3 expression in renal tubules sparing glomeruli. In tumor tissue, galectin-1 showed high expression in 47 (70.1%) and low expression in 20 (29.9%) of specimens. Galectin-3 had high expression in 15 (22.4%) and low expression in 52 (77.6%) of specimens. Significant association was detected between expression of galectin-1 and galectin-3 and the type of RCC (P = 0.032) and (P = 0.006), respectively. Significant inverse association was detected between the expression of galectin-3 and the presence of tumor haemorrhage and necrosis (P = 0.014) and (P = 0.039), respectively. CONCLUSION: Galectin-1 and galectin-3 are overexpressed in RCC with different percentage in different subtypes. Galactin-1expression is more in tumor tissue than surrounding renal parenchyma suggesting that it has a carcinogenic role. Galectin-1 and galectin-3 overexpression in chromophobe RCC suggests that they may have diagnostic role.

Diffusion weighted magnetic resonance imaging in bladder cancer, is it time to replace biopsy?

INTRODUCTION: To assess if the apparent diffusion coefficient (ADC) value of magnetic resonance imaging (MRI) can discriminate between the cell type, histological grade and improve staging of urinary bladder cancer (BC). MATERIAL AND METHODS: 102 patients with urinary bladder masses underwent MRI using a 1.5 T machine. T2 weighted and diffusion weighted imaging (DWI) using b values of 0, 150, 500 and 1000 s/mm2 were done. The ADC values of bladder masses were measured. These values were correlated with the histopathologic results. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of T2WI, DWI and T2WI plus DWI for detecting bladder lesions were evaluated. RESULTS: The cut-off ADC value for diagnosing malignant bladder wall pathologies was ≤1 x 10-3 mm2/s with 94.5% sensitivity and 87.5% specificity. The mean ADC value of different malignant cell types was statistically insignificant. A significant difference in ADC values was found between G1 and G3 (P = 0.000), G2 and G3 (P = 0.045) but not between G1 and G2 (p = 0.066). Staging accuracy for differentiation between invasive and non-invasive lesions was nearly the same for all MRI data sets. For differentiation between organ confined (pT1-pT2) and non-organ confined lesions (pT3-pT4), staging accuracy was better in T2WI plus DWI (83%) as compared to DWI alone (77%) or T2WI alone (75%). CONCLUSIONS: Adding DWI and the ADC value to T2WI improve the accuracy of MRI in BC detection and staging. However, at this time point, MRI cannot replace transurethral resection (TUR) biopsy or distinguish sharply between all different histologic grades and cell types.

Immunohistochemical analysis of PTEN, HER2/neu, and ki67 expression in patients with gastric cancer and their association with survival.

BACKGROUND: Considering the poor prognosis of patients with gastric cancer, molecular diagnostic and prognostic markers for this cancer should be established. The aims of our study were to assess the correlations between PTEN, HER2/neu, and Ki67 expressions and clinicopathological factors of gastric cancer patients in upper Egypt, as well as their influence on OS and DFS. PATIENTS AND METHODS: In this descriptive-analytic study, 42 patients with gastric carcinoma treated by postioerative chemoradiation between 2004 and 2014. Pathological review was done. Immunohistochemical staining and evaluation were performed. RESULTS: All the studied markers were significantly correlated with increased TNM stage. Her2/neu overexpression and positive Ki67 expression were significantly associated with histological grade. High percentage of positive Her2/neu and Ki67expression was found in gastric carcinoma tissue samples which lack PTEN expression. The one-year OS rate for the entire group (n=42) was 77.4%, whereas the DFS rate was 45%. Pathological T stage PTEN status significantly affected both OS (p=0.029 and 0.027 respectively) and DFS (p=0.006 and 0.012 respectively) rates. Multivariate Cox analyses showed that only pathological T stage was an independent prognostic factor affecting OS (P=0. 007, HR: 2.02; 95% CI: 1.2-3.38)and DFS(P<0.0001, HR: 2.69; 95% CI: 1.54-4.69). CONCLUSION: All the studied molecular markers, was significantly correlated with pathological T stage that significantly affected both OS and DFS rates. These findings indicate that these markers have an important role in gastric cancer growth and dissemination so these markers can be used as a prognostic biomarker. In addition, therapies targeting Her2 and PTEN may help develop novel therapeutics for gastric cancer.