Dilaver Demirel

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.

Malignant tumors arising in endometriosis: clinical-pathological study and flow cytometry analysis

BACKGROUNDnMalignant transformation to endometriosis is a well documented phenomenon that occurs most commonly in the ovaries with cancer arising in extra-ovarian endometriosis being a rare event.nnnMETHODSnA retrospective clinical-pathological evaluation of eleven cases with malignant tumors arising in endometriosis was performed to evaluate the prognostic impact of various factors. Nuclear DNA content (ploidy) was assessed through flow cytometric study.nnnRESULTSnOvarian origin was identified in eight cases and three were associated with extra-ovarian endometriosis. Histologic type was endometrioid carcinoma in ten patients. The eleventh case had high grade endometrial stromal sarcoma. All tumors were diploid with no relation to stage, grade, or clinical outcome. The S-phase fraction (SPF) was analyzed in nine patients and no correlation could be demonstrated with any histologic parameters or clinical outcome.nnnCONCLUSIONSnThe DNA content seems to have no association with the classical prognostic parameters in these cases.

Primary retroperitoneal mucinous cystadenoma with a sarcoma-like mural nodule: an immunohistochemical study with histogenetic considerations and literature review.

Primary retroperitoneal mucinous cystadenomas (PRMCs) are extremely rare tumors and their association with sarcoma-like mural nodules (SLMNs) has not been described thoroughly. The aim of this study is to characterize the gross and microscopic features and the immunohistochemical profile of the first case of PRMC with SLMN and to discuss the differential diagnosis of SLMNs. The literature related to primary retroperitoneal mucinous tumors is reviewed in an attempt to clarify the histogenesis of the epithelial and sarcomatoid components of the associated mural nodules. A 34-yr-old woman presented with a 14-cm retroperitoneal cystic lesion with a 6-cm mural nodule. An immunohistochemical study with a panel of 19 antibodies and a histochemical study for mucin stains were performed. The epithelial component of the PRMC showed positive staining for cytokeratin (CK) 7, CK AE1/3, epithelial membrane antigen, carcinoembryonic antigen, and calretinin. The neoplasm was not immunoreactive for CK 20, CK 5/6, and the other antibodies used in this study. In addition, it stained positively for mucin by mucicarmine, periodic acid-Schiff, and Alcian blue. The stromal cells of the cyst showed estrogen receptor positivity. SLMN cells were negative for all CKs and other epithelial markers used in the study, but they showed diffuse positive staining for vimentin and CD68, and positive staining for Ki-67 was demonstrated in 25% of these cells. The immunohistochemical and histochemical profiles of PRMC were similar to those of ovarian mucinous neoplasms and the mesothelium. The formation of SLMNs seems to be related to subepithelial hemorrhage and some reactive epithelial changes near the mural nodules. The specific immunohistochemical and morphologic features of SLMNs are helpful in differentiating them from malignant mural nodules, including true sarcomas, osteoclast-rich undifferentiated carcinomas, and carcinosarcomas. Such a differentiation is critical in view of its significant impact on the management of these neoplasms, particularly in young patients who desire to preserve their fertility.

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

Abstract 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-1β and the leukocyte count. Results. When the results of serum amylase, lipase, TNF-α and IL-1β 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.

Trimetazidine significantly reduces cerulein-induced pancreatic apoptosis

OBJECTIVEnAcute 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.nnnMETHODSnThirty-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)-1β, 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.nnnRESULTSnIn the acute pancreatitis group IL-1β, amylase, lipase and leukocyte levels were elevated and pancreatic histopathological evaluation revealed a diagnosis of acute pancreatitis IL-1β 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).nnnCONCLUSIONnIn this study, we showed that trimetazidine treatment significantly decreases the levels of IL-1β, 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.

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

OBJECTIVEnAlthough 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.nnnMATERIAL AND METHODSnThis study was conducted on 140 patients who had applied to Gülhane Military Medical Academy, Haydarpaşa 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.nnnRESULTSnAccording 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.nnnCONCLUSIONnIn placental trophoblasts, decreased P-cadherin immunoreactivity plays a role in the aetiopathogenesis of spontaneous abortion.

Could S6K1 immunopositivity be used to distinguish early and advanced stages of endometrioid endometrial adenocarcinoma

OBJECTIVEnTo assess whether the immunopositivity of S6K1, a crucial effector of the mTOR signaling pathway, varies between early-stage low-grade and advanced-stage high-grade endometrial endometrioid adenocarcinoma (EEA) as well as to discuss its prognostic significance.nnnMATERIAL AND METHODSnA total of 22 normal endometrial tissue samples (Control group) and 41 EEA specimens (Study group) were enrolled in the study, and all the samples underwent immunohistochemical staining for S6 kinase alpha (S6K1). The study group was further evaluated in two subgroups; stage 1A, grade 1 (Group 1) and stage ≥1A, grade 2 or 3 (Group 2). Group 2 patients were considered as a poor prognosis for EEA. The samples were examined by two independent pathologists. Statistical analyses were performed using the Students t-test for continuous variables, the Chi-square test for categorical variables, and one-way analysis of variance for the comparison of multiple variables.nnnRESULTSnThe immunopositivity rate for all the included EEA patients was 56.1%, whereas none of the 22 normal endometrial tissue samples revealed immunoreactivity for S6K1. The immunopositivity rates were significantly different between Groups 1 and 2 [38.1% (8/21) and 75.0% (15/20), respectively, p=0.039]. When S6K1 positivity was used as a criterion of poor prognosis in EEA, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated to be 62%, 75%, 72%, and 65%, respectively (OR: 4.9 and 95% CI: 1.3-18.7).nnnCONCLUSIONnS6K1 was positive in the majority of EEAs and malignancies at an advanced stage. Higher grade disease had a significantly higher rate of S6K1 positivity. S6K1 immunopositivity appears to be a promising method to predict poor prognosis in EEA.

Mucosal Malignant Melanoma of Inferior Concha and Nasal Septum: A Case Report with Mutation Analysis

Mucosal Malignant Melanoma of Inferior Concha and Nasal Septum: A Case Report with Mutation Analysis nNasal and paranasal Mucosal Malign Melanoma’s occurs 0.5% of all Malign Melanomas. Sinonasal Mucosal Malign Melanoma often arises from lateral nasal wall and septum. We present molecular features (BRAF, NRAS, c-KIT and PDGFRA mutations) of a sixty-three-year-old male patient with primary sinonasal mucosal malignant melanoma with rarely localized synchronously in inferior concha and nasal septum. The patient underwent melanoma resection via endoscopic approach with negative surgical margins, right functional neck dissection and 6000 Gy radiotherapy after surgery. There was no tumor recurrence and metastasis at the ten month follow-up of the patient. Pathological studies revealed no mutations in the KIT gene (exons 9, 11, 13, 17 and 18), NRAS gene (exons 2 and 3), BRAF gene (exon 15) and the PDGFRA gene (exons 12 and 18) in this tumor. Our case is also unique with its concurrent localization in the nasal septum and inferior turbinate and with no mutations in BRAF, NRAS, c-KIT and PDGFRA genes. Primary sinonasal mucosal malignant melanomas are biologically different from cutaneous malignant melanomas and molecular features of these tumors need more investigation.

The Potential Role of Human Papillomavirus in Colorectal Carcinoma

Chong PP, Asyikin N, Rusinahayati M, et al (2010). High We read the article entitled “The aetiological role of human papillomavirus in colorectal carcinoma: an iranian population- based case control study” presented by Ranjbar et al. (2014) with great interest. Their results, by nested PCR using MY09/11 and GP5+/GP6+ primers, revealed the possible role of high risk Human Papillomavirus (HPV) types in colorectal cancer. Although the number of positive HPV cases were small the frequencies of HPV types were found to be slightly different from previous studies performed in different geographic and ethnic populations. We would like to thank to authors for their valuable contribution. It has been known that most of the HPV detection methods including MY09/MY11 and GP5+/GP6+ have been introduced to detect common or high risk HPV types seen in uterine cervix, and none of those methods have the ability to detect most of the other HPV types (Chong et al., 2010, Sahiner et al., 2012). For this reason, to assess presence of not only common but also rare HPV types in colorectal cancer specimens, in our recent study we have used different HPV detection primer sets including consensus primers and novel broad spectrum primer sets covering more than 100 HPV types in a study with 93 colorectal carcinoma patients. Our preliminary results revealed presence of HPV DNA in 3 cancer tissues. Genotyping was performed by Sanger sequencing, and we have found the HPV Types 16, 18, and an unclassified HPV type which was identical to the reported sequence of HPV isolate FAIMVS6.3 found in a patient with skin cancer by Forslund et al. (2003). As best of our knowledge, this is the second reported case infected with HPV isolate FAIMVS6.3. Considering the known number of HPV types is about 200, consensus primers can detect only about 30 different HPV types which are mostly limited to common HPV types seen in uterine cervix, and it is insufficient for detecting rest of the HPV types which may have an oncogenic potential for colorectum. Our results demonstrated that HPV genotypes other than common mucosal types may also involve in etiology of colorectal cancer. Therefore, it is obvious that the selected method for detecting HPV DNA would influence the frequencies and type distributions of HPV infections in colorectal cancer. Finally, to find out the real frequencies and type distributions of HPV types, studies performed with different primer sets covering a wide range of HPV types are required.