Upregulation of microrna-106a is associated with microsatellite instability status in colorectal cancer

Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kanserin (KRK) oluşmasına neden olan genetik bir durumdur. Sporadik KRK’larda MSI görülme sıklığı, prognoza olan etkisi literatürde çelişkilidir. Bununla birlikte MSI’ya sahip KRK’larda standart kemoterapi yetersiz kaldığı için yeni tedavi seçeneklerine ihtiyaç duyulmaktadır. micoRNA’lar (miRNA) kanserleşme sürecinde görev alan ve tanıda, prognozda ve tedavide belirteç olarak kullanılan küçük RNA molekülleridir. Mevcut çalışmada, Türk popülasyonuna ait sporadik gelişen KRK’larda MSI’nın görülme sıklığının tanımlanması ve bu tümörlerde miRNA’ların ekspresyon farklılıklarının belirlenmesi amaçlanmıştır. Çalışmada, sporadik KRK tanısı almış 63 hasta değerlendirildi. Hastalara ait arşiv tümör ve normal dokularından DNA ve RNA izolasyonları yapıldı. DNA örneklerinden fragment analizine dayalı MSI testi gerçekleştirildi. qRT-PCR kullanılarak 38 farklı miRNA’nın ekspresyon profili incelendi. 63 hastada MSI görülme oranı %23.8 olarak belirlendi. MSI ve mikrosatellit stabil (MSS) tümörler karşılaştırıldığında, MSI tümörlerde, miR-124 ve miR-106a’nın yüksek ve miR-145’in ise düşük ekspresyon gösterdiği belirlendi (p<0.05). Bununla birlikte miR-106a’nın yüksek ekspresyonunun cerrahi sonrası nüks gelişimi ile ilişkili olduğu saptandı (p=0.002). Elde edilen bulgular ışığında miR-106a’nın özellikle MSI genotipine sahip KRK tümörlerde hedeflenmesi ile KRK hastalarında yeni tedavi protokollerinin oluşturularak nüks oluşumunun engellenebileceğini öngörülmüştür.Microsatellite instability (MSI) is a genetic condition that results from errors in DNA repair genes and causes colorectal cancer (CRC). The incidence of MSI in sporadic CRCs and its effect on prognosis are contradictory in the literature. However, since standard chemotherapy is insufficient in CRCs with MSI, new treatment options are needed. micoRNAs (miRNAs) are small RNA molecules that take part in the cancer process and are used as markers in diagnosis, prognosis and treatment. In the study, it is aimed to define the prevalence of MSI in sporadically developing CRCs belonging to the Turkish population and to determine the expression differences of miRNAs in these tumors. 63 patients diagnosed with sporadic CRC were evaluated in the study. DNA and RNA isolations were made from archive tumor and normal tissues of the patients. MSI test was performed based on fragment analysis from DNA samples. The expression profiles of 38 different miRNAs were examined using qRT-PCR. In 63 patients, the incidence of MSI was determined as 23.8%. When MSI and microsatellite stable (MSS) tumors were compared, it was determined that miR-124 and miR-106a showed high expression and miR-145 low expression in MSI tumors (p <0.05). However, high expression of miR-106a was found to be associated with postoperative recurrence (p=0.002). In the light of the findings obtained, we think that by targeting miR-106a especially in CRC tumors with MSI genetype, recurrence can be prevented by creating new treatment protocols in these tumors

Effects of Systemic and Local Interferon Beta-1a on Epidural Fibrosis

Study DesignLevel 1 randomized controlled study.PurposeTo investigate the effects of systemic and local interferon-beta-1a (IFN-β-1a) on prevention of epidural fibrosis using histopathological parameters.Overview of LiteratureEpidural fibrosis involves fibroblastic invasion of nerve roots into the epidural space. Formation of dense fibrous tissue causes lumbar and radicular pain. Many surgical techniques and several materials have been proposed in the literature, but no study has assessed the effect of IFN-β-1a on prevention of epidural fibrosis.MethodsForty-eight adult female Sprague-Dawley rats were divided into six groups of eight: sham group, control group, systemic 44 μg IFN-β-1a group and 22 μg IFN-β-1a group (after laminectomy and discectomy, 0.28 mL and 0.14 mL IFN-β-1a applied subcutaneously three times for a week, respectively), local 44 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.28 mL IFN-β-1a on the surgical area), and local 22 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.14 mL IFN-β-1a on the surgical area). All rats were sacrificed after 4 weeks and groups were evaluated histopathologically.ResultsCompared with sham and control groups, significantly less epidural fibrosis, dural adhesion, and fibroblast cell density were observed in the local and systemic 44 μg IFN-β-1a groups. No other differences were evident between the local and systemic groups.ConclusionsIFN-β-1a is effective in preventing epidural fibrosis with systemic and local application

Histologic evaluation of gastric biopsies according to Sydney classification and searching the relation of H. Pylori and cell proliferation

Çalışmanın amacı; kronik gastrit tanısı almış olguların biyopsi materyallerinin Sydney sistemine göre değerlendirilmesi, parametrelerin yaş gruplarında ve Helikobakter pilori (H. pilori) yoğunluğuna göre karşılaştırılmasıdır. Ayrıca H. pilori enfekte olgularda immunohistokimyasal Ki67 protein ekspresyonunun ve intestinal metaplazili olgularda tip tayinin yapılmasıdır. Çalışmaya alınan 427 olgunun Hematoksilen-Eozin boyalı kesitleri Sydney skorlaması ile değerlendirildi. İntestinal metaplazili 127 olguya Periyodik Asit Schiff / Alcian Blue (PAS/AB) (pH=2,5) ve High Iron Diamine / Alcian Blue (HID/AB) (pH=2,5) kombine boyaları uygulanıldı. İntestinal metaplazilerde Filibe sınıflamasına göre tiplendirme yapıldı. H. pilori pozitif 99, H. pilori negatif 30 olguda ise hücre proliferatif indeksini değerlendirmek için Ki67 uygulandı. Kronik gastrit tanısı alan olguların % 23’ünde H. pilori yoğunluğuyla korele akut inflamasyon izlendi. İntestinal metaplazi ve atrofi antrum lokalizasyonunda daha fazla mevcuttu. H. pilori kolonizasyonu antrumda 31 – 60 yaş aralığında daha fazla saptandı. En sık tip II intestinal metaplazi gözlenirken; 61 yaş üstü grubunda intestinal metaplazi ve atrofi daha yüksek oranda izlendi. Yoğun derecede H. pilori bulunan olgularda, bakteri bulunmayan olgulara göre Ki67 proliferatif indeksi anlamlı olarak yüksek izlendi. Sonuçta; bölgemizde H. pylori oranı gelişmiş ülkelere göre hafif derecede yüksek, H. pilori kolonizasyonu antrumda daha sık iken, 31 yaş altı grubunda pangastrit varlığı, artan yaşla birlikte atrofi ve intestinal metaplazi oranın H. pilori varlığından bağımsız arttığı, H. pilori infeksiyonunun gastrik epitelyal proliferasyonu antrum ve korpusta arttırdığı saptandı. Patolog gastrit tanılı olguların raporlarında H. pilori’nin varlığı, kronik inflamasyon, nötrofil polimorf aktivitesi, glandular atrofi ve intestinal metaplaziyi belirtmelidir. Kanserlerdeki temel patolojinin kontrolsüz proliferasyon olduğu dikkate alınırsa, çalışmamızda H. pilori’ye bağlı karsinogenezde artmış proliferasyonun önemli rolü bulunduğu düşünülen savlarla uygunluk saptandı.The aim of this study is to evaluate the materials of gastric biopsies in cases diagnosed as chronic gastritis according to Sydney system and comparing the parameters according to age groups, density of Helicobacter pylori (H. pylori) demonstrating the immunohistochemical expression of protein Ki67 and pointing out of type in cases with intestinal metaplasia. Hematoxilen-Eozin stained sections of 427 cases were evaluated by means of Sydney score. The combine stain of Periodic Acid Schiff / Alcian Blue (PAS/AB) (pH=2,5) and High Iron Diamine / Alcian Blue (HID/AB) (pH=2,5) were applied to 127 cases with intestinal metaplasia. The typing of intestinal metaplasia was done according to Filibe classification. Ki67 immunohistochemical stain was applied to 99 cases which were H. pylori positive and to 30 cases which were H. pylori negative to evaluate the cell proliferation. Acute inflammation was correlating with the density of H. pylori in 23% of chronic gastritis cases and intestinal metaplasia and atrophy were under in antrum localization. H. pylori colonization was greater in antrum between the 31–60 age group. Most frequently type 2 intestinal metaplasia has been observed; in age group higher than 61, intestinal metaplasia and atrophy have been observed higher ratio. In cases which contain high levels of H.pylori, contain the proliferative index of Ki67 significantly higher than cases which do not contain bacteria. In conclusion; we determined that H. pylori rate is a little higher in our region according to developed countries, H. pylori colonization is more common in antrum. In under 31 age group pangastritis existence is more common, atrophy and intestinal metaplasia rate increases independently from existence of H. pylori, with increase of age. H. pylori infection increases gastric epithelial proliferation antrum and corpus. Pathologist should report the existence of H. pylori shows and determines chronic inflammation, activity of neutrophil polymorph, glandular atrophy and intestinal metaplasia in chronic gastritis cases. If the basic pathology in cancer, which is an uncontrolled proliferation, in our study we determined concomitance with the theories that defend the H. pylori effect on increased cell proliferation

Liver metastasis of breast carcinoma: An unusual presentation and growth pattern

Breast carcinoma is one of the tumors that frequently metastasize to the liver. Extramedullary hematopoiesis (EMH) usually occurs due to insufficient medullary hematopoiesis. In this case report, we present a female patient with sinusoidal breast carcinoma metastasis and extramedullary hematopoiesis in liver biopsy. A 63-year-old female patient with history of breast carcinoma was admitted to our center with respiratory distress. Pleural effusion was detected and thoracentesis was planned. Treatment was given after detection of non-mycobacterial tuberculosis bacillus in the thoracentesis fluid. Antibiotherapy was terminated due to elevation of liver enzymes and bilirubin. The patient's clinical status was evaluated and treatment was re-initiated. The patient did not have any mass lesion in the liver. Tru-cut biopsy was performed to evaluate a possible tuberculosis involvement in the liver. The diagnosis of metastatic breast carcinoma located in the sinusoidal area and cholestatic liver with extramedullary hematopoiesis foci was given using the histomorphological, immunohistochemical and histochemical findings. Radiological evaluation has an important role in staging of malignancies. However, it should be kept in mind that hepatic metastases may present without formation of a mass lesion, and unexpected laboratory results of cases without abnormal radiological features should raise the suspicion of a metastasis. Such materials should be evaluated in detail by making multiple serial sections in the pathology laboratory. Rare metastatic tumor growth patterns not causing a mass lesion such as sinusoidal or portal pattern, should also be kept in mind

A Mimicker of Gallbladder Carcinoma: Cystic Gastric Heterotopia with Intestinal Metaplasia

Heterotopic gastric mucosa in the gallbladder is an unusual entity and is usually clinically silent. We report a 75-year-old female patient who presented with intermittent upper abdomial pain radiating to the back. Abdominal imaging studies showed a sessile polypoid lesion and a gallstone in the gallbladder. Gallbladder carcinoma was suspected and cholecystectomy performed. Intraoperative frozen section examination suggested mucinous tumor, suspicious for malignancy. However, the permanent sections revealed aberrant gastric tissue consisted of gastric pyloric and fundic glands of heterotopic gastric mucosa with intestinal metaplasia in the gallbladder

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS