Prognostic value of expression levels of miR-148a, miR-152 and HLA-G in colon cancer.

Aberrant expression of human leukocyte antigen G (HLA-G), an immunosuppressive molecule, has been observed in various cancer types. The exact mechanism of HLA-G expression is unclear. HLA-G expression is associated with low expression levels of microRNA (miR)-148a and miR-152. To the best of our knowledge, the prognostic value of the expression levels of miR-148a, miR-152 and HLA-G has not been investigated in colon cancer. The aim of the present study was to investigate the relationship between the presence of HLA-G molecules and the expression levels of miR-148 and miR-152 in colon cancer. In addition, the association of both HLA-G and miR expression with survival results and clinicopathological data was determined. An immunohistochemical method was used for detection of HLA-G expression in the tumor tissues and adjacent healthy tissues of 108 patients with colon cancer. Reverse transcription-quantitative PCR was used for miR analysis. HLA-G was expressed in 82 (75.9%) of the cancer samples, and there was no staining in normal tissues. HLA-G expression >20%, which was found in 41.7% (45/108) of the patients with colon cancer, was significantly positively associated with patient survival (P=0.039). Additionally, miR-148a levels were lower in the tumor tissues compared with the adjacent healthy tissues. No differences were found for miR-152 expression. In addition, mir-148a levels were found to be significantly lower (P=0.001) in HLA-G-positive tumor tissues than HLA-G-negative tumor tissues, but no such relationship was found for miR-152 levels. The presence of HLA-G expression was associated with poor survival outcomes. HLA-G is one of the prognostic factors in colon cancer, and decreased miR-148a expression in colon cancer tissues may be associated with HLA-G-mediated carcinogenesis.

Evaluation of PCA3 and multiparametric MRI's: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL.

OBJECTIVE: To analyze the contribution of multiparametric MRI and PCA3 assay, predecision of initial biopsy in PSA level between 3-10 ng/mL patients with normal digital rectal examination(DRE). MATERIALS AND METHODS: PSA level 3-10 ng/mL, patients, with normal DRE results and no previous prostate biopsy history, were included in this study. Each patient underwent multiparametric MRI one week before biopsy. Urine sample taking for PCA3 examination preceded the biopsy. Systematic and targeted biopsies were conducted. Patients with high PSA levels were seperated into two groups as: high PCA3 scored and low PCA3 scored. Then each group was divided into two sub-groups as: MRI lesion positive and negative. Tumor incidence, positive predictive values(PPV) and negative predictive values(NPV) were calculated. RESULTS: 53 patients were included between February 2013 and March 2014. Mean age 61.22 ± 1.06. Mean PSA value 5.13 ± 0.19 ng / mL. Mean PCA3 score 98.01 ± 23.13 and mean prostate size was 48.96 ± 2.67 grams. Fourty nine patients had both PCA3 score and multiparametric MRI. The PCA3's PPV value was 58.33%. If multiparametric MRI lesions are added to high PCA3 scores , the PPV appears to elevate to 91.66%. NPV of PCA3 was 96%. NPV was 95% when there was no lesion in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% , specificity was 95% respectively. CONCLUSION: Adding multimetric MRI can also support biopsy decision for patients with high PCA3 value. When PCA3 value is low, patients can be survailled without any need to take a MRI.

TMPRSS2-ERG gene fusion in Turkish patients with localized prostate cancer: results of radical prostatectomy specimens.

OBJECTIVE: Our aim was to evaluate and determine the frequency of Transmembrane protease, serine 2 (TMPRSS2)-ERG fusion in Turkish patients with clinically localized prostate cancer by using immunohistochemistry and reveal its relationship with clinicopathologic variables. MATERIAL AND METHODS: Radical prostatectomy specimens of 99 patients, who underwent radical retropubic prostatectomy for localized cancer, between January 2002 and December 2011 were analyzed in the study. To detect ERG fusions, monoclonal ERG antibodyclone ID: EPR3864 (Epitomics, San Diego, CA, USA) and monoclonal anti-ERG antibody (9FY) (BiocareMedical, LLC, USA) were used. The immunistochemical expression of ERG protein was assessed as positive or negative regardless of stain intensity. Patients' age, total and primary Gleason scores, PSA levels, prostate volumes, tumor volumes, tumor stages and perineural invasion status were analysed retrospectively. Total fusion rate and correlation between the variables and fusion were evaluated. RESULTS: Mean age, prostate volume, tumor volume, PSA value of 99 patients were 62.02 years (±5.93), 50.02 cc (±20.67), 3.19 cc (±4.16), and 9.34 ng/mL (±3.37) respectively. TMPRSS2-ERG fusion was seen in 46 (46.5%) of 99 patients. When the variables analysed with independent samples t test to predict fusion (+) status, none of them was found to be statistically significant. When evaluated by logistic regression analysis for (+) or (-) status, only tumor stage was found to be statistically significantly correlated with fusion (p=0.049). CONCLUSION: The incidence of TMPRSS-ERG fusion in patients with localised prostate cancer in our study with Turkish population was found as 46.5%. Only tumor stage correlated with TMPRSS2-ERG fusion.

Evaluation of PCA3 and multiparametric MRI's: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL

ABSTRACT Objective To analyze the contribution of multiparametric MRI and PCA3 assay, pre- decision of initial biopsy in PSA level between 3-10 ng/mL patients with normal digital rectal examination(DRE). Materials and Methods PSA level 3-10 ng/mL ,patients, with normal DRE results and no previous prostate biopsy history, were included in this study. Each patient underwent multiparametric MRI one week before biopsy. Urine sample taking for PCA3 examination preceded the biopsy. Systematic and targeted biopsies were conducted. Patients with high PSA levels were seperated into two groups as: high PCA3 scored and low PCA3 scored. Then each group was divided into two sub-groups as: MRI lesion positive and negative. Tumor incidence, positive predictive values(PPV) and negative predictive values(NPV) were calculated. Results 53 patients were included between February 2013 and March 2014.Mean age 61.22 ± 1.06. Mean PSA value 5.13 ± 0.19 ng / mL. Mean PCA3 score 98.01 ± 23.13 and mean prostate size was 48.96 ± 2.67 grams. Fourty nine patients had both PCA3 score and multiparametric MRI. The PCA3’s PPV value was 58.33%. If multiparametric MRI lesions are added to high PCA3 scores , the PPV appears to elevate to 91.66%. NPV of PCA3 was 96%. NPV was 95% when there was no lesion in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% , specificity was 95% respectively. Conclusion Adding multimetric MRI can also support biopsy decision for patients with high PCA3 value. When PCA3 value is low, patients can be survailled without any need to take a MRI.

Schwannoma of the penis: a case report / Schwannoma del pene: presentación de un caso

Penile schwannoma is a rare tumor arising from the neurilemmal cells reported only a few in the literature. Here we report a case of penile schwannoma in a young adult treated successfully by local excision (AU)

Schwannoma del pene es un tumor poco común que surge de las células del neurilema, se han registrado solo unos pocos en la literatura. Aquí se presenta un caso de schwannoma del pene en un adulto joven tratado con éxito mediante extirpación (AU)

Molecular alterations in malignant blue nevi and related blue lesions.

Malignant blue nevi (MBN) are extremely rare dermal melanocytic tumors that arise in association with atypical cellular blue nevi (ACBN), cellular blue nevi (CBN), common blue nevi (BN), or de novo. The frequency of BRAF, NRAS, and KIT mutations in malignant melanoma varies according to histological subtype and localization. These mutations are rarely observed in blue nevi, which have recently been shown to carry activating mutations in GNAQ/GNA11 genes. Only few small molecular studies of MBN have been published. The aim of the present study was to analyze in MBN and related blue lesions such as ACBN, CBN, and BN the prevalence of BRAF, NRAS, KIT, GNAQ, and GNA11 gene mutations and their association with clinicopathological features. We included in our study 12 MBN, 6 ACBN, 29 CBN, and 35 common BN diagnosed between 1996 and 2014. Sanger sequencing method was used for mutation analysis. Overall, GNAQ exon 5 mutation was the most frequent alteration (46 %), in 2 of 12 (17 %) MBN, 1 of 6 (17 %) ACBN, 22 of 29 (76 %) CBN, and 13 of 35 (37 %) common BN. BRAF V600E and GNA11 exon 5 mutations were respectively detected in 3 of 12 (25 %) and in 2 of 12 (17 %) MBN while none in ACBN, CBN, and common BN. None of the cases harbored NRAS exon 2/3, KIT exon 9/11/13/17/18, or GNAQ/GNA11 exon 4 mutations. GNAQ gene exon 5 mutations are rare in MBN and ACBN but frequent in CBN and common BN. Remarkably, BRAF V600E and GNA11 exon 5 mutations were only detected in MBN, whereas none were found in ACBN, CBN, or common BN. Our data contribute new elements to the limited data on molecular alterations in MBN.

BRAF, KIT, NRAS, GNAQ and GNA11 mutation analysis in cutaneous melanomas in Turkish population.

BACKGROUND: KIT and mitogen-activated protein kinase cascade are important for melanomagenesis. In the present study, we analyzed the frequency of BRAF, NRAS, KIT, GNAQ and GNA11 gene mutations and investigated their association with clinicopathological features of melanomas in Turkish population. MATERIALS AND METHODS: Forty-seven primary cutaneous melanomas were included in our study. Sanger sequencing method was used for mutation analysis in all cases. RESULTS: Mean age was 62.1 (29-101) years. Female:male ratio was 17:30. Among 47 melanomas, 14 (29.8%) BRAF, 10 (21.3%) NRAS, 4 (8.5%) KIT and 1(2.1%) GNAQ gene mutations were detected. Two of the KIT mutations were found in acral lentiginous melanoma (ALM). In the head and neck region, mutation frequency was significantly lower than in other locations (P = 0.035). The only GNAQ gene mutation (p.Q209L) was detected in a melanoma arising from blue nevus located on the scalp. None of the melanomas harbored NRAS exon 2, KIT exon 13/17/18, GNAQ exon 4 and GNA11 exon 4/5 mutations. Overall mutation frequency did not show significant difference between metastatic (8/14, 57.1%) and nonmetastatic (18/33, 54.5%) patients. We did not observe any significant association between mutation status and gender or age of various patients. CONCLUSIONS: Our results support that BRAF and NRAS gene mutations are common in cutaneous melanomas. The activating mutations of KIT gene are rare and especially seen in ALM. GNAQ and GNA11 mutations are infrequent in cutaneous melanomas and may be associated only with melanomas arising from blue nevus.

MicroRNA expression profile in patients with stage II colorectal cancer: a Turkish referral center study.

BACKGROUND: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. MATERIALS AND METHODS: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). CONCLUSIONS: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

Trimetazidine significantly reduces cerulein-induced pancreatic apoptosis.

OBJECTIVE: Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are still very limited. We aimed to investigate the efficacy of trimetazidine on cerulein-induced pancreatic apoptosis and histopathological and biochemistrical consequences of acute pancreatitis. METHODS: Thirty-two Wistar albino rats were randomized into four groups (group 1: control group; group 2: acute pancreatitis group; group 3: acute pancreatitis and trimetazidine treatment group; group 4: placebo group). Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 µg/kg) four times at one-hour intervals. Trimetazidine was prepared in suspension form. In group 3, after gas anesthesia, trimetazidine was administrated to rats via a catheter. Serum interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, amylase, lipase and leukocyte levels, pancreatic apoptotic status and pancreatic Schoenberg scores were determined for all groups. Results are given as the mean ± SD. A value of P<0.05 was accepted as statistically significant. SPSS for Windows v15.0 was used for statistical analyses. RESULTS: In the acute pancreatitis group IL-1ß, amylase, lipase and leukocyte levels were elevated and pancreatic histopathological evaluation revealed a diagnosis of acute pancreatitis IL-1ß amylase and lipase levels and pancreatic inflammation were decreased significantly in the trimetazidine group (P<0.01). White blood cell counts and TNF-α concentrations for the trimetazidine group and the acute pancreatitis group were not significantly different. Trimetazidine significantly reduced apoptosis in pancreatic tissues and Schoenberg scores were also significantly reduced (P<0.05). CONCLUSION: In this study, we showed that trimetazidine treatment significantly decreases the levels of IL-1ß, amylase and lipase reduces pancreatic apoptosis and ameliorates the histopathological findings of cerulein-induced acute pancreatitis. Trimetazidine could be a new therapeutic option in the early treatment of acute pancreatitis.

miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer.

PURPOSE: We examined expression profiles of 16 micro RNAs (miRNAs) in triple negative breast cancers to identify their potential as biomarkers for lymph node metastasis. METHODS: The expression profiles of miR-9, miR-21, miR-30a, miR-30d, miR-31, miR-34a, miR-34c, miR-100, miR-122, miR-125b, miR-146a, miR-146b, miR-155, miR-181a, miR-200c, and miR-205 were examined by using real-time quantitative reverse transcription polymerase chain reaction in tumor samples and corresponding benign breast tissues. Their associations with histopathological features and prognostic parameters were assessed. RESULTS: When compared with the expression in benign breast tissues, seven of the miRNAs (miR-31, miR-205, miR-34a, miR-146a, miR-125b, miR-34c, and miR-181a) were downregulated more than 1.5-fold in tumor tissues, whereas, only miR-21 was found to be upregulated more than 1.5-fold in tumor tissues. Although miR-200c levels were decreased only 1.12-fold in tumor tissues, the reduced expressions of miR-200c and miR-205 were significantly associated with lymph node metastasis (p=0.021 and p=0.016, respectively). CONCLUSION: Our results demonstrate that miR-205 and miR-200c expression levels may be useful in predicting lymph node metastasis in triple negative breast cancer patients.

Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats.

AIM: Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. MATERIALS AND METHODS: Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1ß and the leukocyte count. RESULTS: When the results of serum amylase, lipase, TNF-α and IL-1ß levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). CONCLUSION: In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

Expression of P-cadherin (cadherin-3) and E-selectin in the villous trophoblast of first trimester human placenta.

OBJECTIVE: Although trophoblastic invasion has a critical role in human placental development, very little is known about them. The aim of the present study was to localise the expression of P-cadherin (cadherin-3) and E-selectin in first trimester placenta. MATERIAL AND METHODS: This study was conducted on 140 patients who had applied to Gülhane Military Medical Academy, Haydarpasa Education Hospital, Department of Obstetrics and Gynaecology between 2005 and 2006. The patients were divided into three groups: ectopic pregnancy group (Group 1), spontaneous abortion group (group 2) and curettage group (group 3 and/or control group). Patients with a history of systemic diseases (such as thrombophilia), a disease or anatomical diagnosis that may cause recurrent abortion or an aetiological factor for ectopic pregnancy were excluded from the study. Paraffin blocks were stained with E-selectin and P-cadherin in accordance with the procedure. Demographic characteristics of patients (patient age, gravida, parity, number of previous abortions, and last menstrual period) and staining intensities were compared using Analysis of Variance (ANOVA) among groups. RESULTS: According to the average scale score of P-cadherin staining of cells, the three groups were statistically different from each other (p=0.0001). This difference stems from statistically significantly lower scores in the spontaneous abortion group than in both the ectopic pregnancy group (p<0.001) and the control group (p<0.001). E-selectin immunostaining showed no positive staining in the groups. CONCLUSION: In placental trophoblasts, decreased P-cadherin immunoreactivity plays a role in the aetiopathogenesis of spontaneous abortion.

Effect of hyperbaric oxygen treatment in a rat model of abdominal aortic aneurysm.

Matrix metalloproteinase (MMP) plays a pivotal role in the pathophysiology of abdominal aortic aneurysms (AAA). Experimental studies have demonstrated that hyperbaric oxygen (HBO2) therapy decreases MMP levels in different tissues. However, the effect of HBO2 therapy on AAA has yet to be investigated. This study aimed to examine the effects of HBO2 on MMPs in an experimental AAA model. The model was implemented with CaCl2 in 12-week-old male Wistar albino rats. The rats were randomized into four groups: Group I: received NaCl (n = 6) (Sham group); Group II: received NaCl and were treated with HBO2 (n = 6); Group III: received CaCl2 (n = 6); and Group IV: received CaCl2 and were treated with HBO2 (n = 6). HBO2 therapy was applied for five of seven days over a period of six weeks. Although in the CaCl2 groups, aortic diameters were significantly higher than the NaCl groups (p < 0.05), there was no difference between pre- and post-HBO2 in the CaCl2 groups (p > 0.05). In the CaCl2 group, the MMP-2 and MMP-9 levels were significantly higher than those in the NaCl group (p < 0.05). HBO2 therapy had no statistically significant effect on the MMP-2 and MMP-9 levels in Groups III and IV. However, it was observed that both levels clearly decreased in Group IV. In conclusion, the study suggested that HBO2 may have favorable effects on MMP levels.

Differential diagnosis of cervical lymphadenitis mimicking malignancy due to tularemia: our experiences.

BACKGROUND: Tularemia is a disease caused by a Gram-negative coccobacillus Francisella tularensis. This bacterium may cause different types of clinical pictures owing to acquisition route and entrance site, such as ulceroglandular, oropharyngeal, glandular, pneumonic, typhoid and ocular forms. Oropharyngeal tularemia (OPT) is the most common form of tularemia in some regions. OPT may cause tonsillopharyngitis followed by cervical lymphadenopathies (LAPs). Without treatment LAP may persist for several months and may mimic other diseases causing cervical LAPs. MATERIALS AND METHODS: A total of six cases of OPT, five male and one female, between 21 and 31 years old, diagnosed serologically and clinically recorded in GATA Haydarpasa Training Hospital were included in this study. Detailed story including the region they lived for last 6 months, their occupation, family and neighborhood story with similar complaints were obtained. Patient data were also obtained from manually written patients files and electronical patient file system. Formalin fixed paraffin embedded tissue blocks of all biopsy material were submitted for polymerase chain reaction (PCR) study for F. tularensis. RESULTS: A total of six cases with head and neck mass following a story of tonsillopharyngitis admitted to different clinics including infectious diseases, ear-nose-throat and internal medicine in our tertiary care hospital. Physical examination revealed immobile, hard, conglomerated unilateral cervical lymphadenopathy in all cases. Histopathological examination revealed granulomatous inflammation in four cases. Acute suppurative inflammatory changes were also seen in two cases. Large necrotic areas mimicking casseifying necrosis were seen in two cases. PCR amplification of F. tularensis genom from isolated deoxyribonucleic acids was successful in five cases. CONCLUSION: Tularemia should be kept in mind in patients with tonsillopharyngitis not responding to penicillins and beta lactam antibiotics. Furthermore, persisting LAPs mimicking tumor with or without the story of previously experienced sore throat or tonsillopharyngitis in past few days or weeks should be evaluated for glandular or OPT. At this point, easily applicable serological tests such as tularemia micro-agglutination tests will confirm the diagnosis of OPT. However, if lymph node were already sampled to exclude especially malignancy or T cell lymphoma, tularemia PCR test may be used to make a certain diagnosis.

CYP1A1 (Ile462Val), CYP1B1 (Ala119Ser and Val432Leu), GSTM1 (null), and GSTT1 (null) polymorphisms and bladder cancer risk in a Turkish population.

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.