Radiation exposure in acute myeloid leukaemia, diffuse large B-cell lymphoma, and multiple myeloma patients in the first year following diagnosis.

Purpose: Radiological examinations are critical in the evaluation of patients with haematological malignancies for diagnosis and treatment. Any dose of radiation has been shown in studies to be harmful. In this regard, we assessed the radiation exposure of 3 types of haematological malignancies (diffuse large B-cell lymphoma [DLBCL], acute myeloid leukaemia [AML], and multiple myeloma [MM]) in our centre during the first year after diagnosis. Material and methods: In the first year after diagnosis we retrospectively reviewed the radiation exposure data of 3 types of haematological malignancies (DLBCL, AML, and MM). The total and median CED value (cumulative effective radiation dose in millisieverts [mSv]) of each patient was used. Each patient's total and median estimated CED value was calculated using a web-based calculator and recorded in millisieverts (mSv). Results: The total radiation doses in one year after diagnosis (CED value) were 46.54 ± 37.12 (median dose: 36.2) in the AML group; 63.00 ± 42.05 (median dose: 66.4) in the DLBCL group; and 28.04 ± 19.81 (median dose: 26.0) in the MM group (p = 0.0001). There was a significant difference between DLBCL and MM groups. Conclusions: In all 3 haematological malignancies, the radiation exposure was significant, especially in the DBLCL group, within the first year of diagnosis. It is critical to seek methods to reduce these dosage levels. In diagnostic radiology, reference values must be established to increase awareness and self-control and reduce patient radiation exposure. This paper is also the first to offer thorough details on the subject at hand, and we think it can serve as a guide for further investigation.

Comparison of Multiparametric and Fast MRI Protocols in Detecting Clinically Significant Prostate Cancer and a Detailed Cost Analysis.

BACKGROUND: Due to the long acquisition time and high cost of multiparametric magnetic resonance imaging (mpMRI), biparametric and, more recently, fast prostate magnetic resonance imaging (fpMRI) protocols have been described. However, there is insufficient data about the diagnostic performance and cost of fpMRI. PURPOSE: To compare the diagnostic performances and cost analysis of fpMRI and mpMRI in clinically significant prostate cancer (csPCA). STUDY TYPE: Retrospective. POPULATION: A total of 103 patients (63 had csPCA) with a mean age of 66.83 (± 7.22) years were included. FIELD STRENGTH/SEQUENCE: A 1.5-T; T1- and T2-weighted turbo spin-echo imaging (T1WI and T2WI), echo-planar diffusion-weighted images, and dynamic contrast-enhanced T1W imaging. ASSESSMENT: Three readers independently evaluated the fpMRI and mpMRI images in different sessions blinded to all patient information. Diagnostic performances of fpMRI and mpMRI were evaluated. Kappa coefficient (κ) was used to determine the interreader and intrareader agreement. A detailed cost analysis was performed for each protocol. STATISTICAL TESTS: Receiver operating characteristics analysis, area under the curve (AUC), and κ test were used. Diagnostic performance parameters were also calculated. RESULTS: Of the 63 malignant index lesions (csPCA), 53/63 of those (84.1%) originated from the peripheral zone and 10/63 lesions (15.9%) originated from the transition zone. The AUC values for fpMRI were 0.878 for reader 1, 0.937 for reader 2, and 0.855 for reader 3. For mpMRI, the AUC values were 0.893 for reader 1, 0.94 for reader 2, and 0.862 for reader 3. Inter and intrareader agreements were moderate to substantial (κ range, 0.5-0.79). The total cost per examination was calculated as €12.39 and €30.10 for fpMRI and mpMRI, respectively. DATA CONCLUSIONS: Fast MRI protocol has similar diagnostic performance with mpMRI in detecting csPCA, and fpMRI can be considered an alternative protocol that could create a lower financial burden on health-care systems. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 6.

The miRNA content of circulating exosomes in DLBCL patients and in vitro influence of DLBCL-derived exosomes on miRNA expression of healthy B-cells from peripheral blood.

BACKGROUND: Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanisms underlying tumor development and progression have not yet been fully elucidated. OBJECTIVE: This study aimed to compare the characteristics of plasma exosomes of DLBCL patients and healthy individuals and to evaluate the exosomal interactions between DLBCL cell lines and normal B-cells. METHODS: Exosome isolation was performed using an ultracentrifugation-based protocol from plasma of 20 patients with DLBCL and 20 controls. The expression of miRNAs from exosome samples was analyzed using a miRNA expression microarray. The presence of exosome-mediated communication between the lymphoma cells and normal B-cells was determined by the co-culture model. RESULTS: A significant increase in plasma exosome concentrations of DLBCL patients was observed. There was also a significant decrease in the expression of 33 miRNAs in plasma exosomes of DLBCL patients. It was determined that normal B-cells internalize DLBCL-derived exosomes and then miRNA expression differences observed in normal B-cells are specific to lymphoma-subtypes. CONCLUSIONS: MiR-3960, miR-6089 and miR-939-5p can be used as the miRNA signature in DLBCL diagnosis. We suppose that the exosomes changed the molecular signature of the target cells depending on the genomic characterization of the lymphoma cells they have originated.

VI-RADS score and tumor contact length in MRI: A potential method for the detection of muscle invasion in bladder cancer.

BACKGROUND: Vesical Imaging Reporting and Data System (VI-RADS) is a useful tool for evaluating muscle layer invasion of bladder cancer (BCa) on magnetic resonance imaging (MRI). PURPOSE: To evaluate the diagnostic performance of bladder MRI to detect the muscle layer invasion of BCa using VI-RADS score and quantitative MRI parameters. METHODS: Preoperative bladder MRI was performed in 73 BCa patients. Two observers independently evaluated the MR blinded to histopathological data and classified the tumors according to VI-RADS criteria. Moreover, the quantitative parameters (maximum tumor diameter; Dmax, tumor contact length; TCL, and tumor apparent diffusion coefficient; ADC values) were independently measured by observers. The diagnostic performance of the VI-RADS score and quantitative values were evaluated by using receiver operating characteristic (ROC) analysis. Interobserver agreement was evaluated using the weighted-kappa coefficient (κ). RESULTS: For the VI-RADS score, the AUC (area under the curve) was 0.968 and accuracy was 90.4% for Observer 1, and AUC was 0.953, accuracy was 89% for Observer 2. The AUC of TCL, TCL/DMax, and ADC values was 0.918, 0.675, and 0.832. In patients with a VI-RADS score ≥ 3, when a threshold value of TCL > 19.5 mm is used as complementary to the VI-RADS score, the accuracy of MRI for Observer-1 increases 100% and 97.26% for Observer-2. There was a good-excellent agreement between the observers in assessing the VI-RADS scores and quantitative parameters. CONCLUSION: Evaluation of bladder MRI using both VI-RADS criteria and TCL is successful and highly reproducible for detecting muscle layer invasion in patients with BCa.

Dose-dependent effects of adalimumab in neonatal rats with hypoxia/reoxygenation-induced intestinal damage.

Tumor necrosis factor-alpha (TNF-α) has an important role in hypoxia/reoxygenation (H/R)-induced intestinal damage. It was shown that blocking TNF-α with infliximab has beneficial effects on experimental necrotizing enterocolitis and hypoxic intestinal injury. However, there is no data about the effect of adalimumab on H/R-induced intestinal damage. Therefore, we aimed to determine potential dose-dependent benefits of adalimumab in such damage in neonatal rats. Wistar albino rat pups were assigned to one of the four groups: control group, hypoxia group, low-dose adalimumab (5 mg/kg/day) treated group (LDAT), and high-dose adalimumab (50 mg/kg/day) treated group (HDAT). On the fourth day of the experiment, all rats except for the control group were exposed to H/R followed by euthanasia. Malondialdehyde (MDA), myeloperoxidase (MPO), TNF-α, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured in intestinal tissue. TAC and TOC values were used to calculate the oxidative stress index (OSI). Histopathological injury scores (HIS) were also evaluated in the tissue samples. MDA levels were significantly lower in the LDAT and HDAT groups (p < 0.001). TNF-α levels were significantly lower in the LDAT group (p < 0.001). OSI was significantly higher in the H/R group than in the control and LDAT groups (p < 0.001). Mean HIS values in the LDAT group were significantly lower than those in the H/R and HDAT groups (p < 0.001). This experimental study showed that low-dose adalimumab appears to have a beneficial effect on intestinal injury induced with H/R in neonatal rats.

The determination of stage in nonmuscle urothelial carcinoma: Staining pattern of caspase-8.

CONTEXT: Urothelial carcinoma (UC) is one of the most frequent epithelial tumors worldwide. AIMS: We aimed to investigate the protein expressions of caspase-8, p53, murine double minute 2 (mdm2), and p14ARF in nonmuscle UCs and to correlate the findings with clinicopathological characteristics. SETTINGS AND DESIGN:: A total of 50 patients who had pTa and pT1 tumors were analyzed. SUBJECTS AND METHODS: The protein expressions of caspase-8, p53, mdm2, and p14ARF were analyzed by immunohistochemistry. STATISTICAL ANALYSIS USED: Chi-square test was done using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA). RESULTS: Cytoplasmic caspase-8 expression was significantly higher in pT1 UCs while nuclear caspase-8 expression was significantly higher in pTa UCs (P = 0.005 and P = 0.011, respectively). Cytoplasmic caspase-8 expression was also higher in high-grade UCs (P = 0.035). The expression of p53, mdm2, and p14ARF was not also related with pathological stage or grade (P > 0.05 for all). The p14ARF expression was related with nuclear caspase-8 expression in most of the patients. Complete agreement among nonmuscle UCs for immunohistochemical expression of p14 and nuclear caspase-8 was seen in 41 cases, and the pairwise kappa agreement value was substantial (κ =0.614). The patients who had recurrence were positive for both p53 and mdm2 or either p53 or mdm2 (P = 0.025). CONCLUSIONS: These results suggested that the staining pattern of caspase-8 might be helpful for determining of the stages in nonmuscle UC. It was also showed that the expression status of p53 and mdm2 were related with the recurrence.

Characterizing the Association Between Toll-like Receptor Subtypes and Nephrolithiasis With Renal Inflammation in an Animal Model.

OBJECTIVE: To show experimentally induced renal stone disease and to evaluate secondary inflammatory responses in vivo, and to characterize changes in the expression of Toll-like receptor (TLR) subtypes in this model. METHODS: Twenty 5- to 6-week-old male Wistar rats were divided into control and hyperoxaluria groups (n = 10 per group) and were supplied with normal water or 1% ethylene glycol, respectively, for 16 weeks. The animals were then placed in metabolic cages, and urine was collected for a 24-hour urine oxalate level evaluation. Following sacrifice, rats were subjected to bilateral nephrectomy and both kidneys were histopathologically evaluated. A 1-mm3 biopsy section from the right kidney of each rat was subjected to real-time polymerase chain reaction of the TLR expression. RESULTS: At the end of week 16, the hyperoxaluria group had a higher mean 24-hour urine oxalate level (1.91) than the control group (0.29) (P <.05) and a remarkably increased deposition of renal CaOx crystals (15/20) than the control group (0/20) (P <.05), which was universally accompanied by inflammation (15/15). Twelve and no rats in the hyperoxaluria and control groups, respectively, had macroscopically visible renal pelvic stones (P <.05). Quantitative real-time polymerase chain reaction revealed significant decreases in the expression of several TLRs, particularly TLR11 and TLR7. Decreases in TLR1, TLR3, and TLR6 expressions and an increase in the TLR2 expression did not differ significantly between the groups. CONCLUSION: We believe that is the first evaluation of TLR expression associated with renal stone formation in an animal model of inflammation. These results might lead to novel TLR-based treatments for nephrolithiasis and related inflammatory renal damage.

Human TLR gene family members are differentially expressed in patients with urothelial carcinoma of the bladder.

PURPOSE: Toll-like receptors (TLRs) have an important role in the activation of both innate and adaptive immunity in response to pathogens and endogenous danger signals from damaged or dying cells. The aim of this study was to determine the relationship between urothelial carcinoma (UC) and TLR expression. BASIC PROCEDURES: Real-time polymerase chain reaction evaluation was made of the messenger RNA expression of TLRs 1-10 in 24 UC samples and 46 nontumoral bladder tissue samples. The levels of proinflammatory cytokines (IL-1ß, IL-6, and IL-8) in the urine samples were also determined with enzyme-linked immunosorbent assay. MAIN FINDINGS: TLR2-7 and TLR10 expressions were significantly higher in UC than in the control group (P<0.05 for all comparisons). No concordance was found between matched tumor tissue and urine samples in terms of TLR expression. IL-1ß, IL-6, and IL-8 levels were significantly higher in urine specimens of patients with UC (P = 0.033, P = 0.001, and P = 0.008, respectively). PRINCIPAL CONCLUSIONS: The results of this study demonstrated that the TLR gene expression profiles reflect the heterogeneity within UC. These results might also prompt further investigation to better understand the role of the TLR gene family expression in the tumor progression of UC.

Effects of endovenous laser ablation on vascular tissue: molecular genetics approach.

BACKGROUND: Endovenous laser ablation (EVLA) is a treatment option for lower extremity varicose veins. In the present study, we investigate to the genetic changes and possibility of living tissue in the saphenous vein wall after the EVLA procedure. METHODS: Eleven saphenous vein grafts were randomized in two groups: (1) 4 cm SVG segments of performed EVLA procedure in study group, (2) 4 cm segments of SVG none performed EVLA procedure in control group. SVG were taken from the remnants of distal saphenous vein grafts prepared for the bypass procedure but not used. SVG was approximately 8 cm in length and was divided into two parts 4 cm in length. One half was exposed to laser energy, while the other half of the same vein graft was untreated as a control. EVLA was performed on complete saphenous veins in the study group. Abnormal genetic changes of the SVG were observed with a Tri-Reagent method and quantified with a Nanodrop™ spectrophotometer. RESULTS: Histopathological changes indicated that the intima including the endothelium was completely necrotized in the study group. It was observed that intimal thermal-energy-induced injury did not reach the media. Histopathological examination showed that homogenous eosinophilic discoloration and coagulation necrosis characterized the laser related thermal damage as well. CONCLUSIONS: In this preliminary study, we found that living tissue remained in the SVG wall after application of laser ablation, and we also detected abnormal genetic changes in the study group compared with the control group.

Effects of Tempol on Experimental Acute Necrotizing Pancreatitis Model in Rats.

AIM: We aimed to investigate the effects of Tempol on local organ damage in an experimental acute pancreatitis model. METHODS: This experimental study was conducted on 40 male Wistar- albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomies and cannulations of the pancreatic duct without acute necrotizing pancreatitis (ANP) (n=10); (ii) Sham + Tempol group, identical to group 1 except for intravenous tempol treatment for 4 hours (n = 10); (iii) ANP group, glycodeoxycholic acid was infused into the pancreatic duct and cerulein was infused intravenously for 6 hours for development of ANP (n=10); and (iv) ANP + Tempol treated group, in addition to the procedure in group 3, rats were administered tempol intravenously for 4 hours (n = 10). Injury of the pancreas was evaluated histopathologically. Malondialdehyde and myeloperoxidase levels of the pancreatic tissue, blood gas analysis, leukocyte and hematocrit levels were measured. Wet/dry weight of pancreatic tissue was also measured. RESULTS: Serum amylase levels, pancreatic tissue malondialdehyde and myeloperoxidase levels, wet/dry weight ratio, pancreatic edema, acinar necrosis, fat necrosis and hemorrhage, inflammation and perivascular infiltration were significantly lower in the ANP + Tempol group compared with the ANP group. CONCLUSION: Tempol infusion reduced local organ damage due to acute necrotizing pancreatitis in this experimental study. These findings demonstrate that tempol has protective effects on local organ damage due to acute necrotizing pancreatitis in rats.

A Newborn with Congenital Mixed Phenotype Acute Leukemia After In Vitro Fertilization.

Congenital leukemia is a rare disease. The majority of cases of this disease are acute myelogenous leukemia (AML). Congenital acute lymphoblastic leukemia (ALL) is rare and most often is of B cell lineage. Rarely, some cases have been designated biphenotypic or mixed phenotype acute leukemia (MPAL). Herein, we report a preterm newborn referred to us as a result of the appearance of blue-violaceous dermal nodules on her body at birth. She was a twin and the product of an in vitro fertilization (IVF) pregnancy. Physical examination showed jaundice, hepatosplenomegaly, and peripheral facial nerve palsy in addition to dermal nodules. Bone marrow aspiration showed 40% blasts of lymphoid lineage; skin biopsy and its immunohistochemistry revealed myeloblastic infiltration of the dermis. Cytogenetic analysis (46,XX), fluorescence in situ hybridization (FISH) analysis, and cranial magnetic resonance were normal. The patient was diagnosed with congenital MPAL, and an association between IVF and congenital leukemia was suggested.

The determination of relationship between "excision repair cross-complementing group 1" (ERCC1) gene T19007C and C8092A single nucleotide polymorphisms and clinicopathological parameters in non-small cell lung cancer.

DNA repair plays a key role in prevention of carcinogenesis and one of the most important DNA repair mechanisms is nucleotide excision repair (NER) pathway. This pathway includes a number of genes such as excision repair cross-complementing group 1 (ERCC1) gene which are responsible for the 5' incision of damaged DNA. A reduced DNA repair capacity associated with ERCC1 mRNA level has been observed in lung carcinogenesis. Two single nucleotide polymorphisms (SNPs) in ERCC1 gene, T19007C (rs11615) and C8092A (rs3212986), reportedly predict to affect the mRNA of ERCC1 in non-small cell lung cancer (NSCLC). To examine the role of two common SNPs in ERCC1 gene further, we conducted this study where 80 cases histopatologically diagnosed as NSCLC were genotyped. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues and two SNPs were analyzed using real-time PCR. The distributions of TT, TC, and CC genotypes of the T19007C SNP were 40, 44 and 16%, respectively. Significantly increased frequency of the patients carrying at least one 19007C allele was observed in early stage compared to advanced stage (P=0.002). And also, the frequency of TC and CC genotypes significantly increased in younger patients compared to older patients (P=0.035). Regarding C8092A SNP, the distribution of CC, CA, and AA genotypes was 38, 51 and 11%, respectively. There was no significant difference in the genotype distribution between C8092A SNP and clinicopathological parameters. This study indicated that harboring at least one 19007C allele may have protective effect in NSCLC.

Protective effects of Ginkgo biloba extract in rats with hypoxia/reoxygenation-induced intestinal injury.

BACKGROUND: The purpose of this study is to investigate the protective effects of Ginkgo biloba extract (EGb 761) in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury. METHODS: One-day-old Wistar albino rat pups (n = 21) were randomly divided into 3 groups: group 1 (control, untreated and not exposed to H/R, n = 7), group 2 (untreated but exposed to H/R, n = 7), and group 3 (EGb 761 + H/R, n = 7). Ginkgo biloba extract was administered (100 mg/kg per day, subcutaneously) to group 3 for 3 days. On the fourth day, all animals except controls were exposed to H/R and were killed 6 hours after H/R. Histopathologic injury scores (HIS), malondialdehyde, glutathione (GSH), GSH-peroxidase (Px) activities, and nitric oxide (NO) levels were measured on intestinal samples. RESULTS: Although the control group had normal HIS, group 2 had grade 3 HIS. In contrast, group 3 had minimal HIS, and these results were significantly better than those of group 2 (P < .001). Malondialdehyde and NO levels of group 3 were significantly lower than those of group 2 (P < .01). Glutathione and GSH-Px activities of group 1 were higher than those of groups 2 and 3 (P < .05). However, there were no significant differences for GSH and GSH-Px activities between groups 2 and 3. CONCLUSIONS: This study showed that hypoxia and NO contributed to the pathogenesis of H/R-induced intestinal injury and that prophylactically administered EGb 761 had a protective effect on bowel injury.

Expression of p16 protein and cyclin D1 in periampullary carcinomas.

OBJECTIVE: The majority of the tumors in periampullary region are pancreatic and ampulla of Vater carcinomas. The aim of this study was to compare histopathological features of ampulla of Vater carcinomas with pancreatic ductal adenocarcinomas and to determine diagnostic and predictive values of p16 protein and cyclin D1 expression. MATERIAL AND METHOD: Tissue samples from pancreatic ductal adenocarcinomas and ampulla of Vater carcinomas were obtained from 31 patients who underwent pancreticoduodenectomy for periampullary carcinoma. The study group was composed of 12 women and 19 men. Their median age was found to be 62.32 years (range 26-85 years). The parameters analyzed in the study included lymph node metastases, perineural invasion, differentiation, duodenal invasion, grade of intraepithelial neoplasia and p16 and cyclin D1 expression in tumoral and peritumoral pancreatic tissues. RESULTS: In both tumor groups, the loss of p16 protein expression was significantly correlated with perineural invasion (p = 0.0001). Perineural invasion was more frequent in the pancreatic ductal adenocarcinoma group than the ampulla of Vater carcinoma group (p = 0.01). When desmoplasia and lymphoplasmacytic stromal infiltration were examined, desmoplastic reaction was significantly higher in pancreatic ductal adenocarcinomas than ampulla of Vater carcinomas (p = 0.01). No significant difference was observed between tumor groups for Cyclin D1 (p > 0.05). CONCLUSION: The results suggest that loss of p16 protein expression may be a sign for poor prognosis in periampullary cancers that is correlated mainly with perineural invasion. Desmoplastic stromal reaction may be a distinctive feature for pancreatic ductal adenocarcinoma compared with ampulla of Vater carcinoma.

IMP3 expression in urothelial carcinomas of the urinary bladder.

OBJECTIVE: Superficial tumors including Ta, Tis, and T1 make up 75% of urothelial carcinomas of the bladder. While the behavior of these superficial urothelial cancers is relatively benign, invasive tumors have a significant mortality rate. However, Ta and T1 tumors might display different biological behavior. There is therefore a great need for biomarkers that can accurately distinguish the behavior of urothelial carcinomas in addition to tumor grade and stage. Our aim was to determine the immunohistochemical expression profile of insulin like growth factor II mRNA binding Protein 3 (IMP3) and its correlation with tumor stage and grade in benign urothelium and bladder urothelial carcinomas. MATERIAL AND METHOD: The expression of IMP3 in 91 patients with benign urothelium (20 cases), low grade invasive (17 cases) / noninvasive (20 cases) urothelial carcinoma and high grade invasive (20 cases) / non-invasive (14 cases) urothelial carcinoma was evaluated by immunohistochemistry in this study. RESULTS: IMP3 was not expressed in benign urothelium, low-grade non-invasive urothelial carcinoma and high grade non-invasive urothelial carcinoma. Expression of IMP3 was found in 11.76% of low-grade invasive urothelial carcinomas and 55% of high grade invasive urothelial carcinomas. Statistical analysis including chi2 tests showed that IMP3 expression of invasive urothelial carcinomas was statistically significant (p < 0.000). CONCLUSION: The detection of IMP3 only in invasive carcinomas although some of them were low grade showed that the expression of IMP3 may be related to aggressive behavior of urothelial carcinomas.

Protective effects of clarithromycin in rats with hypoxia/reoxygenation-induced intestinal injury.

BACKGROUND: This study was designed to determine the role of oxidative stress, nitric oxide (NO), and glutathione-related antioxidant enzymes in rat pups with hypoxia/reoxygenation (H/R)-induced bowel injury and to evaluate the potential benefits of prophylactic clarithromycin. METHODS: One-day-old Wistar albino rat pups (N = 21) were randomly divided into 3 groups: group I (control), group II (exposed to H/R), and group III (clarithromycin + H/R). Clarithromycin was administered (40 mg/kg) subcutaneously to group III for 3 days. On the fourth day, all rats except controls were exposed to H/R and were killed at 6 hours after H/R. Histopathologic injury scores (HIS), malonyldialdehyde, glutathione (GSH), glutathione-peroxidase (GSH-Px) activities, and NO levels were measured on intestinal samples. RESULTS: Whereas there was no difference for malonyldialdehyde levels among groups, HIS and NO levels were higher in group II than groups I and III (P < .05). However, GSH and GSH-Px activities were lower in group II than groups I and III (P < .05). Clarithromycin significantly increased GSH and GSH-Px activities and reduced HIS and NO levels in group III. CONCLUSION: This study showed that oxidative stress and NO contributed to the pathogenesis of H/R-induced bowel injury and that clarithromycin had a protective effect on bowel injury owing to anti-inflammatory and antioxidant effects.

No strong association between HER-2/neu protein overexpression and gene amplification in high-grade invasive urothelial carcinomas.

The generation of urothelial carcinoma is caused by the accumulation of various molecular changes, as in most malignancies. There are conflicting data about the status of HER-2/neu oncogene in urothelial carcinomas. The aim of this study was to determine the status of HER-2/neu oncogene in high-grade invasive urothelial carcinoma of urinary bladder both in protein and DNA level. We evaluated HER-2/neu protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH) and real-time quantitative PCR in paraffin-embedded samples of high-grade invasive urothelial carcinoma obtained from 36 patients. Polysomy 17 was also assessed by FISH. Immunohistochemically, HER-2/neu protein overexpression was observed in 22 (61.1%) tumors (ten tumors with score 3+ and 12 with score 2+). Fourteen of 36 tumors (38.9%) were evaluated as negative (score 0 or 1+). Complete concordance between FISH and the PCR was seen in all of the samples scored as 0 and 1+ by IHC. HER-2/neu gene amplification was observed in three of 27 (11.1%) tumors by FISH (nine samples were non-informative) and in eight of 36 (22.2%) tumors by the PCR. The complete concordance between HER2-2/neu protein overexpression and gene amplification was seen only in three of 27 tumors. Polysomy 17 was seen in nine tumors (33.3%). The results indicated that, in contrast to breast cancer, there was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.