Neuroserpin As an Adjuvant Therapy for Hypothermia on Brain Injury in Neonatal Hypoxic-Ischemic Rats.

OBJECTIVE: We aimed to assess the effects of neuroserpin and its combination with hypothermia on hypoxic-ischemic (HI) brain injury in neonatal rats. Neuroserpin is an axon-secreted serine protease inhibitor and is important for brain development, neuronal survival, and synaptic plasticity. STUDY DESIGN: Male Wistar-Albino rats on postnatal day 7 (P7) were randomly divided into five groups: sham group (n = 10), (HI; n = 10), hypoxic-ischemic hypothermia (HIH; n = 10), hypoxic-ischemic neuroserpin (HIN; n = 10), and hypoxic-ischemic neuroserpin-hypothermia (HINH; n = 10). The P7 rat brain's maturation is similar to a late preterm human brain at 34 to 36 weeks of gestation. HI was induced in rats on P7 as previously described. A single dose of 0.2 µM neuroserpin (HINH and HIN) or an equivalent volume of phosphate-buffered saline (sham, HIH, and HI) was administered intraventricularly by a Hamilton syringe immediately after hypoxia. In the follow-up, pups were subjected to systemic hypothermia or normothermia for 2 hours. Euthanasia was performed for histopathological evaluation on P10. Apoptosis was detected by caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and was counted in the hippocampus. RESULTS: In comparison to the HI group, the TUNEL-positive and caspase-3-positive neurons in the sham, HIN, HIH, and HINH groups were considerably lower (13.4 ± 1.0 vs. 1.9 ± 0.9, 6.0 ± 0.9, 5.3 ± 1.6, and 4.0 ± 1.1; p < 0.001) and (13.5 ± 1.7 vs. 1.2 ± 0.7, 9.1 ± 2.7, 4.8 ± 1.0, and 3.9 ± 1.6; p < 0.001). HIN, HIH, and HINH, compared to the sham group, showed more TUNEL-positive and caspase-3-positive neurons (6.0 ± 0.9, 5.3 ± 1.6, 4.0 ± 1.1 vs. 1.9 ± 0.9 and 9.1 ± 2.7, 4.8 ± 1.0, 3.9 ± 1.6 vs. 1.2 ± 0.7; p < 0.001). The HINH group (synergistic effect) had significantly fewer TUNEL-positive neurons and caspase-3-positive neurons than the HIN group (4.0 ± 1.1vs. 6.0 ± 0.9 and 3.9 ± 1.6 vs. 9.1 ± 2.7; p < 0.001). CONCLUSION: Our study showed that both neuroserpin alone and as an adjuvant treatment for hypothermia may have a neuroprotective effect on brain injury. KEY POINTS: · Neuroserpin decreased brain injury.. · Neuroserpin showed a synergistic effect when used as an adjuvant treatment for hypothermia.. · The neuroprotective effect of neuroserpine was related to its antiapoptotic properties..

Prognostic value and morphological findings of overexpression of glypican-3 in hepatocellular carcinoma.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the seventh most common cancer all worldwide and is second in cancer-related deaths. In HCC, whose prognosis is still not good despite current treatments, there is a need for prognostic markers as well as early diagnosis. Glypican (GPC)-3 has been proposed as a potential serologic and histochemical marker specific to HCC. This study aimed to determine the relationship between GPC3 overexpression and HCC prognosis and clinicomorphologic features. MATERIALS AND METHODS: In total 152 patients who were diagnosed as a result of hepatectomy, lobectomy or liver transplantation were enrolled. The patients were divided into two groups, GPC3-positive (overexpression) (>10%) and GPC3-negative (<10%). The demographic data of the patients, tumor characteristics and survival times were recorded. RESULTS: Survival was significantly lower in the GPC3+ group. In the multivariate analysis, hepatitis C, AFP, tumor number, tumor focality, portal vein tumor thrombosis and GLP3 positivity were found to be independent risk factors for survival. CONCLUSION: Our study shows that GPC3 overexpression is a poor prognostic factor in HCC. GPC3 positivity were found to be an independent risk factor for survival.

Cardiophrenic and costophrenic lymph node resection via subxiphoid approach only

When enlarged cardiophrenic lymph nodes (CPLN) are resected the impact on survival is still uncertain, but resection contributes to accurate staging and complete gross resection in advanced ovarian cancer. CPLN resection can be performed via video-assisted thoracic surgery or transabdominally through the subxiphoid or transdiaphragmatic routes. The subxiphoid approach is used to reach the prepericardiac nodes located in the anterior mediastinum. The transdiaphragmatic route is used to remove the costophrenic and supradiaphragmatic paracaval lymph nodes located in the middle and posterior mediastinum, respectively. However, the transdiaphragmatic approach necessitates diaphragm opening and, in most cases, liver mobilization. Costophrenic nodes can be resected through the subxiphoid route in appropriate patients without opening the diaphragm. Thus, the subxiphoid approach may be preferred to remove the costophrenic lymph nodes, in cases in whom diaphragm resection is not anticipated, and especially when the resection procedure is planned to include the prepericardiac nodes. In this video article, we present the method of resecting both prepericardiac and costophrenic lymph nodes using only the subxiphoid approach in a case of advanced ovarian cancer. The subxiphoid virtual space between the pericardium and diaphragm was developed. The observed and palpated CPLNs were dissected and excised from the prepericardiac and right latero-cardiac spaces. Thereafter, diaphragm peritoneum beneath the right costophrenic nodes was dissected. After identifying any enlarged costophrenic nodes by palpation, the sternal and costal diaphragmatic attachments were incised and the right latero-cardiac space was extended. When the single enlarged node was reached, it was grasped and pulled with curved-ring forceps and ultimately resected.

Slug and Vimentin downregulation at the metastatic site is associated with Skip-N2 metastasis of lung adenocarcinoma.

OBJECTIVE: Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. MATERIALS AND METHODS: Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples. RESULTS: Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses. CONCLUSION: The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.

Protective effect of dapagliflozin against cyclosporine A-induced nephrotoxicity.

This study aimed to reveal the possible protective effect of dapagliflozin (DAPA) against acute kidney damage due to cyclosporine A (CsA). Thirty-two mice with an eight-week-old Balb\c albino strain were divided into four groups: control group, CsA group, DAPA group, and CsA + DAPA group. On day 9 of treatment, the animals were decapitated, and bilateral nephrectomy was performed. Oxidative stress and apoptosis were evaluated with caspase-3 activity, total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde (MDA), myeloperoxidase (MPO), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the right kidney resection material. The left kidney resection material was evaluated histopathologically. CsA increased caspase-3 activity, Bax, TOS, MDA, TAS, and MPO levels, and the administration of DAPA with CsA significantly reduced this increase in levels (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). CsA decreased Bcl-2 levels, and administration of CsA + DAPA significantly increased Bcl-2 levels compared with only CsA administration (p < 0.001). Additionally, administration of DAPA significantly reduced the histopathological findings (parenchymal inflammation, hyaline cast formation, vacuolization, and lysis of renal tubular cells) caused by CsA. DAPA reduces oxidative stress, apoptosis, and histopathological damage caused by CsA in renal tissue.

Prognostic and predictive value of EZH2 expression and the tumor immune microenvironment in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare and lethal type of skin cancer characterized by frequent recurrences and metastases. In view of the lack of a proven treatment option for MCC, we immunochemically evaluated the presence of Merkel cell polyomavirus (MCPyV), PD-1, PD-L1, CD8, and EZH2 on slides prepared from tumor tissues of 13 patients with MCC, and examined their association with disease progression and overall survival. PD-1 was expressed on tumor infiltrating lymphocytes (TILs) in 92.3% of the patients. None of the tumor cells expressed PD-L1. CD8 levels were higher in MCPyV-positive tumors. Interestingly, higher CD8 levels correlated with better overall survival (p = 0.025), while higher EZH2 expression correlated with metastasis/recurrence (z = -1.396, p = 0.089). However, low EZH2 expression was associated with poor overall survival (χ2 = 3.745, Cramer V = 0.537, p = 0.086). These findings suggest that EZH2 plays a significant role in MCC and may be a promising therapeutic target.

Clinicopathologic characteristics and prognosis comparison of the uterine high grade endometrial carcinomas.

OBJECTIVES: Grade 3 endometrioid adenocarcinomas (G3 EAC), type two endometrial carcinomas (Type 2 EC), and also uterine carcinosarcomas (UCS) are considered as high-grade endometrial adenocarcinomas. The aim of this study was to compare the clinicopathologic features and survival of patients with UCS, G3 EAC, Type2 EC. MATERIAL AND METHODS: We included two hundred and thirty-five patients in this study. Patients were divided into three groups according to the type of tumor as uterine G3 EAC (group 1, n = 62), Type 2 EC (serous, clear and mixed types; group 2, n = 93), and UCS (group 3, n = 80). We compared the groups according to age, initial symptom, surgical approach, stage, myometrial invasion (MI), lymph node invasion (LNI), lymphovascular space invasion (LVSI), adjuvant therapy, and survival. When comparing the survival outcomes the Kaplan-Meier analysis was performed. RESULTS: The groups were similar according to age, menopausal status, nulliparity, initial symptoms, stage, LVSI, and LNI. Positive cytology was determined significantly more in group 3. There was a significant difference between the groups in terms of myometrial invasion degree. Optimal cytoreduction was similar among the groups. The primary adjuvant treatment was chemotherapy for UCS and Type2 EAC whereas radiotherapy was the main adjuvant treatment for G3 EAC. There were no significant differences among the groups according to overall survival (OS) (p = 0.290). CONCLUSIONS: Although the survival difference among the groups can not be revealed, these patients have different clinical and pathological features and they should be considered as different groups.

Primary melanoma of the urinary tract; Clinicopathologic and molecular review of a case series.

Primary melanoma of the urinary tract is a very rare and aggressive cancer. It accounts for less than 1% of all the melanoma cases, making it difficult to histopathologically diagnose and manage. We present a retrospective case series of eight primary urinary tract melanoma with clinical, pathological, and molecular findings to add more insight to this challenging disease. These cases were evaluated for histopathological, immunohistochemical, and molecular features of melanoma that were most commonly found in the urethra, followed by those in the bladder and ureter. Identification of nested growth patterns and in situ melanocytic components at cell edges are helpful in the histopathological diagnosis of amelanotic or hypomelanotic tumors. Our results indicate that urinary tract melanoma has several molecular traits, such as gene expression patterns. Genetic mutations may be related to metastasis, as well as provide targets for the management programs.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

Prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in uterine carcinosarcoma.

OBJECTIVE: The aim of this study was to evaluate the clinical and prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) in uterine carcinosarcoma (UCS). STUDY DESIGN: Formalin-fixed, paraffin-embedded tissue samples from 59 cases with UCS were analyzed. PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical approach, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were evaluated. The Kaplan-Meier and Cox proportional hazards models were used to compare the outcomes and prognostic factors. RESULTS: PD-1 expression in tumor tissue and microenvironment was detected in 15 (25 %) and 18 (30 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 15 (25 %) and 12 cases (20 %), respectively. PD-L1 expression in tumor was associated with longer survival and median survival was 38 and 15 months in cases with and without PD-L1 expressions, respectively (p = 0.019). Lymphovascular space invasion (LVSI) (p = 0.014), myometrial invasion (p = 0.008) and PD-L1 expression were found to be prognostic for UCS's. PD-L1 expression was found to be an independent good prognostic factor with Cox regression analysis (OR 3.9; 95 % CI: 1.4-11.0) for overall survival. CONCLUSION: PD-1 and/or PD-L1 expression are important due to their expressions in one fourth of the cases with UCS and PD-1/PD-L1 blockade may be a new avenue in UCS.

The prognostic analysis of the some clinicopathological parameters and gene protein expressions in malignant mesothelioma.

INTRODUCTION: Mesothelioma is an aggressive tumour that originates in serous surfaces. The primary end point of this study was to invastigate the relationship of progression free survival (PFS) and overall survival (OS) with the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels in the tumour tissue of pleural and peritoneal mesothelioma cases. MATERIALS AND METHODS: The study included 53 patients diagnosed with mesothelioma between 2005 and 2016. The cases were separated into 2 groups as pleural and peritoneal. The effects on OS and PFS were examined of the c-Met, EGFR, PTEN, PDGFR-alpha, PI3K/AKT and mTOR expression levels and also clinicopathological parameters and the treatments given. In the statistical analysis of the data obtained, IBM SPSS vn 20.0 software was used. RESULT: Of the 53 patients included in the study, 39 (73.6%) were diagnosed with pleural mesothelioma and 14 (26.4%) with peritoneal mesothelioma. According to the c-Met and mTOR expression, OS and PFS of the peritoneal cases with high expression (2+, 3+) was seen to be significantly better than that of the peritoneal cases with low expression (0, 1+) (p<0.05). According to the PDGFR expression, OS and PFS of the pleural cases with low expression (0, 1+) was seen to be significantly better than that of the pleural cases with high expression (2+, 3+) (p<0.05). CONCLUSIONS: The examination of c-MET, PDGFR-alpha and m-TOR expression in the in the tumor tissue of mesothelioma cases may be important in determining prognosis.

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer.

PURPOSE: The aim of this study was to evaluate prognostic importance of programmed death-1 (PD-1) and/ or programmed death-ligand 1 (PD-L1) expressions in type 2 endometrial cancer. Study design Formalin-fixed, paraffin-embedded tissue samples from 53 cases with type 2 endometrial cancer were analyzed. One-third of our cases had serous adenocarcinoma (32%), 11 had clear cell (21%) and 25 had mixed-type adenocarcinoma (47%). PD-1 and PD-L1 expressions in tumor tissue and microenvironment were detected by immunohistochemistry. Clinical and pathological characteristics including age, stage, initial symptom, surgical procedure, myometrial invasion, lymphovascular space invasion (LVSI), lymph node invasion, adjuvant therapy, and survival were reviewed. The Kaplan-Meier and Cox proportional hazards models were used to evaluate the prognostic factors. RESULTS: PD-1 expression in tumor tissue and microenvironment was detected in 22 (42%) and 28 (53%) cases, respectively. PD-L1 expression was detected in tumor and microenvironment in 8 (15%) and in 15 cases (28%), respectively. Expression of PD-1 and PD-L1 expressions in tumor area was associated with shorter survival (p = 0.006 and 0.001, respectively) but PD-1 and PD-L1 expressions in microenvironment were not found to be related with survival. PD-1 (p = 0.006) and PD-L1 expressions (p = 0.001) in addition to LVSI (p = 0.005), myometrial invasion (p = 0.015), lymph node involvement (p = 0.019), and suboptimal cytoreduction (p = 0.042), were found to be associated with poor prognostic indicators. PD-1 and PD-L1 expressions in tumor and lymph node involvement were determined as independent prognostic factors. CONCLUSION: PD-1 and PD-L1 expressions in type 2 endometrial cancers were found to be poor prognostic indicators.

Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung.

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.

PD-1 and PD-L1 expression in thymic epithelial tumours and non-neoplastic thymus.

AIMS: We explored the relationships between programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression and the pathological and clinical features of thymic epithelial tumours and thymic hyperplasia. METHODS: We evaluated PD-1 and PDL-1 expressions within epithelial and microenvironmental components in thymic epithelial tumours (n=44) and thymic hyperplasias (n=8), immunohistochemically. We compared the results with demographic, clinical and histopathological features of the cases. RESULTS: We found 48% epithelial expression and 82.7% microenvironment expression for PD-1 and 11.5% epithelial expression and 34.6% microenvironment expression for PD-L1. There was no PD-1 expression, in either the epithelial or microenvironment, in the thymic hyperplasia group. PD-1 and PD-L1 positivity was more significant in thymic epithelial tumours than thymic hyperplasia. Patients with PD-1-positive microenvironments exhibited significantly shorter mean estimated survival time than their negative counterparts. CONCLUSION: These findings suggest that anti-PD-1 and anti-PD-L1 therapies may benefit patients due to high release of PD-1 and PD-L1 in thymic epithelial tumours.

Myeloid Neoplasia and Lymphoblastic Lymphoma with Eosinophilia After Radioactive Iodine: A Case Report.

BACKGROUND: Thyroid cancer is the most common endocrine cancer, with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with a genetic predisposition or radioactive iodine used in the treatment. CASE REPORT: A 65-year old male patient was operated on for thyroid papillary cancer. He received radioactive iodine on two occasions postoperatively. After six years, he presented with malaise and fatigue with leukocytosis and eosinophlilia. The physical examination revealed inguinal lymphadenopathies and splenomegaly, after examining the bone marrow and lymph node biopsies, he was diagnosed with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukaemia/lymphoma. CONCLUSION: Leukaemia and other haematological malignencies may develop after radioactive iodine treatment. Patients with radioactive iodine ablation history should be monitored for a long time.

What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts.

OBJECTIVE: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

Prevalence of cytogenetic abnormalities in chronic lymphocytic leukemia in the southern part of Turkey.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western populations. CLL has a wide range of clinical presentations and varied outcomes. For CLL, cytogenetic assessment is essential for estimating prognoses and determining the treatment of choice. The fluorescence in situ hybridization (FISH) technique is widely used for genetic assessment due to its high sensitivity. AIM: This study aimed to evaluate the frequencies of deletions of 13q14.3, 17p13.1, 11q22.3, and 13q34 and of trisomy 12 and to observe their effects on survival in 226 Turkish CLL patients using FISH analysis. RESULT AND CONCLUSION: The frequencies of abnormalities were 65.4% for del 13q14.3, 39.8% for del 17p13.1, 19% for del 11q22.3 (del ATM), and 15.9% for trisomy 12. No patients had a 13q34.3 aberration. Our results are partially consistent with literature findings. However, certain conflicts with prior results were observed, particularly with respect to the high prevalence of 17p13.1 deletions and the enhanced survival of patients with such deletions. These inconsistencies may represent population-based differences in the genetic epidemiology of CLL.

Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas.

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy in recent years. The aim of this study is to evaluate the PD-1/PD-L1 expressions in sarcomas and to determine association between PD-1/PD-L1 expressions and clinical/pathological properties in some sarcoma subtypes. Formalin-fixed, paraffin-embedded tissue samples from 65 cases with sarcomas were analyzed. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions in tumor tissue and microenvironment, separately. PD-1 expression in tumor tissue and microenvironment was detected in 11 (17 %) and 8 (12 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 19 (29 %) and 20 cases (30 %), respectively. None of the 5 Ewing sarcomas involving bone showed PD-1/PD-L1 expression, while 2 of 3 cases with Ewing sarcomas involving soft tissue showed PD-1 and PD-L1 expression. Among 5 cases with Kaposi sarcoma, four showed PD-1 and/or PD-L1 expression in tumor or microenvironment. PD-1/PD-L1 expressions were detected 3 of 6 cases with pleomorphic sarcoma, 2 of 4 cases with peripheral nerve sheath tumors and 1 of 4 cases with synovial sarcoma. Interestingly, strongest PD-1/PD-L1 expressions in our study group were detected in 2 sarcoma cases with the history of giant cell tumor. PD-1 and PD-L1 expressions are up to 30 % of the cases with sarcomas. It may be rational to target programmed death pathway in Kaposi sarcoma, pleomorphic sarcoma and peripheral nerve sheath tumors. Strong expression of PD-1/PD-L1 in cases with previous giant cell bone tumor has been found to be interesting and must be studied in giant cell tumor samples.