Central nervous system (CNS) tumours have devastating effects and are recurrent, with dismal prognosis (gliomas) or life‐threatening by the compression effect (meningiomas). This disease's aetiology remains debatable. Over the last decade, the hypothesis that human viruses may be implicated in these tumours has been proposed. In this study, our aim is to examine the presence of 11 viruses in the most frequent CNS primary tumours. Using polymerase chain reaction (PCR), we assessed the viral presence in archived, paraffin‐embedded tumour tissues from 114 patients with glioma and meningioma and in the brain tissue from 40 controls lacking tumour pathology. We focused on candidate neuro‐oncogenic types (herpesviridae and polyomaviruses) and on human papillomavirus (HPV). HPV presence, for which involvement in these tumours was hardly investigated, was found to be associated with both tumour categories compared with controls (glioma, p = 0.032; meningioma, p = 0.032), whereas the presence of the neuro‐oncogenic viruses was found in a negligible number of both categories, suggesting a lack of association with the tumour presence. Moreover, our study reveals a positive correlation between HPV presence and glioma malignancy, and a negative correlation with meningioma grading. Our results suggest that the presence of HPV seems to be significantly associated with primary tumours of the CNS and its meninges.

Background Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 +/- cetuximab in the PETACC8 study. Methods Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade ≥3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS. Table . 549P Overall analysis DFS OS HR [95%CI] p HR [95%CI] p Anticoagulants Intake vs no 1.33 [1.10–1.62] .003 1.34 [1.07–1.67] .01 Antidiarrheals Intake vs no 0.87 [0.73–1.04] .12 0.78 [0.63–0.96] .02 Cardiovascular trts Intake vs no 1.20 [1.03–1.41] .02 1.28 [1.07–1.54] .01 Antidiabetics Intake vs no 1.37 [1.07–1.76] .01 1.45 [1.09–1.92] .01 Conclusions Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification PETACC8; 2005-003463-23. Legal entity responsible for the study Federation Francophone de Cancerologie Digestive, Dijon. Funding Merck and Sanofi. Disclosure J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.

Esthesioneuroblastoma (ENB), also called olfactory neuroblastoma, is a cancerous tumor originating from the olfactory neuroepithelial cells frequently invading the brain through the cribriform plate. The optimal therapy is the multimodality treatment involving a group of physicians trained in different medical specialties. Establishing a careful histopathological diagnostic and treatment planning based on a multidisciplinary approach is of paramount importance. The treatment of ENB correlates with the extent of the lesion, with surgery being the mainstay of therapy followed by postoperative irradiation. Surgery, when complete, image-verified and associated with radiation therapy results in long-term survival and presents a very low probability of illness recurrence. We present the case of a 46-year-old female with ENB, who was operated on in the Clinic of Neurosurgery of the National Institute of Neurology and Neurovascular Diseases in Bucharest, Romania, through a bifrontal craniotomy approach. Gross total resection of the intracranial extent was performed. The pathological diagnosis revealed an aggressive olfactory neuroblastoma. Three weeks after discharge from hospital, the tumor was completely resected through a lateral rhinotomy performed by an otorhinolaryngologist. Six weeks later, the patient received adjuvant therapy (radiotherapy and chemotherapy). The outcome was favorable, with no tumor recurrence at 20 months postoperatively. Our case demonstrates that even when dealing with a visibly aggressive tumor, a correct diagnosis, accurate classification and grading along with appropriate therapy ensure a favorable outcome.

Genetic research has shaped the inflammatory bowel disease (IBD) landscape identifying nearly two hundred risk loci. Nonetheless, the identified variants rendered only a partial success in providing criteria for the differential diagnosis between ulcerative colitis (UC) and Crohn’s disease (CD). Transcript levels from affected intestinal mucosa may serve as tentative biomarkers for improving classification and diagnosis of IBD. The aim of our study was to identify gene expression profiles specific for UC and CD, in endoscopically affected and normal intestinal colonic mucosa from IBD patients. We evaluated a panel of 84 genes related to the IBD-inflammatory pathway on 21 UC and 22 CD paired inflamed and not inflamed mucosa and on age-matched normal mucosa from 21 non-IBD controls. Two genes in UC (CCL11 and MMP10) and two in CD (C4BPB and IL1RN) showed an upregulation trend in both noninflamed and inflamed mucosa compared to controls. Our results suggest that the transcript levels of CCL11, MMP10, C4BPB, and IL1RN are candidate biomarkers that could help in clinical practice for the differential diagnosis between UC and CD and could guide new research on future therapeutic targets.

Lissencephaly-1 (Lis1) protein is a dynein-binding protein involved in neural stem cell division, morphogenesis and motility. To determine whether Lis1 is a key factor in glioblastoma, we evaluated its expression and function in CD133+ glioblastoma cells. Global, Lis1 gene expression is similar in glioblastoma and normal samples. Interestingly, immunohistochemistry data indicate increased Lis1 expression colocalized with CD133 in a subset of glioma cells, including the tumor cells with perivascular localization. Lis1 gene expression is increased up to 60-fold in CD133 positive cells isolated from primary cultures of glioblastoma and U87 glioblastoma cell line as compared to CD133 negative cells. To investigate the potential role of Lis1 in CD133+ glioblastoma cells, we silenced Lis1 gene in U87 cell line obtaining shLis1-U87 cells. In shLis1-U87 cell culture we noticed a significant decrease of CD133+ cells fraction as compared with control cells and also, CD133+ cells isolated from shLis1-U87 were two times less adhesive, migratory and proliferative, as compared with control transfected U87 CD133+ cells. Moreover, Lis1 silencing decreased the proliferative capacity of irradiated U87 cells, an effect attributable to the lower percentage of CD133+ cells. This is the first report showing a preferential expression of Lis1 gene in CD133+ glioblastoma cells. Our data suggest a role of Lis1 in regulating CD133+ glioblastoma cells function.

was 39% (95% CI 21-57).No significant correlation was found between clinical outcome measures and the MGMT promoter methylation status or IDH1/2 mutation status.CONCLUSION: Axitinib has single-agent activity in patients with recurrent GB; upfront combination of axitinib and LOM did not significantly increase progression-free or overall survival in patients with recurrent glioblastoma.Adding CCNU to axitinib after progression seems to result in improved PFS compared to upfront combination therapy. P08.

GFAP-δ, the delta isoform of the glial fibrillary acidic protein, is particularly expressed in the subventricular zone (SVZ) of the brain. GFAP-δ positive cells in the SVZ co-express the neural stem cells (NSCs) marker nestin. According to the theory of glioma oncogenesis, transformation of a cell population with stem features which resides in the SVZ could be the origin of astrocytomas. Moreover, it is known that cancer stem cells promote tumor invasion in cerebral astrocytomas. Therefore, we investigated the immunostaining of GFAP-δ and nestin in cerebral astrocytomas and evaluated the correlation between the positive cell ratio of these markers and the neuroimaging features associated with tumor invasion in forty-four cases of grade II, III and IV cerebral astrocytomas (World Health Organization's classification). Tissue samples were obtained by stereotactic biopsies in all cases. According to the preoperative neuroimaging criteria, tumors were categorized into highly invasive and low invasive. Most of the low-grade and high-grade astrocytomas express GFAP-δ and nestin. The positive cell ratio of GFAP-δ and the positive cell ratio of nestin were statistically significantly higher in highly invasive tumors compared with low-invasive tumors (p < 0.05). Altogether, these results suggest that GFAP-δ and nestin could be clinically relevant markers associated with tumor invasiveness in cerebral astrocytomas.

Routine histopathological criteria are poor predictors of the outcome in meningiomas. The present study tried to determine if some adhesion cell molecules could be helpful in assessing the histological aggressiveness in meningiomas of all grades. Our series comprised 113 cases, WHO grade I (n=53), WHO grade II (n=47) and WHO grade III (n=13). Three cases of meningeal non-meningothelial tumors (hemangiopericytoma, hemangioblastoma and fibrosarcoma) were also studied as control tissue. Immunohistochemistry for CD44, CD54, E-cadherin, progesterone receptor (PGR) and Ki67 was performed. CD54 was for the first time systematically assessed in meningiomas of all three grades of malignancy. CD44 and CD54 were expressed in 58.4 and 31.72% of cases, respectively. CD54 expression showed a direct correlation with the degree of histological anaplasia and Ki67 values. More than half of cases (58.11%) were negative for E-cadherin, mostly the anaplastic ones, which also showed less positive areas for this marker. Cell adhesion molecules were not significantly related to a particular histological type and proliferating potential of meningiomas. Overall, CD54 as well as E-cadherin could be used as additional aggressiveness indicators aside the classical ones. On the other way, Ki67 once again confirmed its significant role in the assessment of meningioma aggressiveness.

Pseudomyxoma peritonei is a rare and poorly understood form of disease characterized by mucin deposits in the peritoneum. The term includes a broad range of neoplasms with different patterns of evolution, from benign to borderline or even to malignant lesions. The disease may be asymptomatic until advanced stages. We present the case of a 65-year-old patient who presented for pain in the right hemiabdomen, after a trauma by falling from small height. Abdominal imaging studies oriented the diagnosis to a traumatic disease. At laparotomy, a mucinous tumor attached to the right colon was discovered. The main particularity of the case is that the origin of the pseudomyxoma could not be identified.

BACKGROUND In patients with high-stage colorectal carcinomas (CRC), anti-EGFR therapy is known to be effective only in cases with a wild-type K-ras gene status. Different procedures have been proposed for such evaluation. MATERIALS AND METHODS The mutation status of K-ras gene, codons 12, 13 and 61 was determined in 250 CRC cases using the pyrosequencing assay. In addition, we compared the performance of the pyrosequencing procedure with that of PCR-RFLP in a subset (n=100) of the CRC samples the latter only in codons 12 and 13. RESULTS Using pyrosequencing, 46.4% of the 250 CRC cases were found mutated. Most mutations were located in codon 12 (36.4% from all cases) and several were located in codon 61 (3.2%). All mutation identified by PCR-RFLP were confirmed by pyrosequencing and, in addition, one more mutated sample was identified in the subset of 100 samples. CONCLUSIONS Both methods are highly specific and can profitably be used in the molecular diagnosis of colorectal cancer in order to establish the adequate therapy.

Tumor infiltrating lymphocytes (TIL), as a microenvironment component were studied in various epithelial tumors, with contradictory results. Recent data about regulatory T-cells (Treg) revealed new explanations for pro- and anti-tumor implications of TIL. Tregs immunoprofile was recently completed with Foxp3 expression. A T-cell fraction (Th) is producing cytokine IL17 and is now considered acting in tumor progression. Our study aimed to analyze immunohistochemically (IHC) Foxp3+ and IL17 expression in resected lung adenocarcinomas, since they could become possible targets in the antitumor immunotherapy. The studied material was represented by paraffin-embedded tumor fragments from 59 patients with TIL identified on HE staining. The antibodies used were Foxp3 and IL17. The statistical analysis used logistical regression on SPSS19 software (Chicago, IL, USA). TIL was usually mild or scarce. A positive statistic correlation resulted between the amounts of TIL in peritumoral and intratumoral location but without correlation to histopathological grading. Foxp3 and IL17 were present in TIL lymphocytes, tumor cells and fibroblasts; IL17 was expressed also in periendothelial cells (PEC). Foxp3 positivity was significantly correlated for lymphocytes÷tumor cells, lymphocytes÷fibroblasts and tumor cells÷fibroblasts, suggesting their concerted action. Tumor cells and lymphocytes Foxp3 expression was inversely correlated with the amount of TIL. Between lymphocytic Foxp3 and PEC IL17, we found a weak negative correlation. The TIL had a quite positive correlation with PEC IL17. In these conditions, Foxp3 could be a mediator of the tumor cells inhibitory aggression upon the immune system and could be used as a molecular target for biological antitumor therapy.

Littoral cell angioma is a rare tumor of the spleen, usually being considered benign and typically discovered incidentally. There are three different modalities of presentation: tumoral splenomegaly, long-standing iron deficient anemia or thrombocytopenia due to hypersplenism. However, some of its manifestations could generate the suspicion of a lymphoma or other more serious condition. We present the case of a 46-year-old man with splenomegaly and iron deficiency anemia. The tumor affected the whole spleen, which was surgically removed. The histopathological examination, together with immunophenotyping, established the diagnosis. Six months after the procedure, the patient is in very good condition. Several differential diagnoses were discussed, as well as the prognostic factors. The case illustrates a rare cause of anemia and the importance of pathology in uncovering such unusual causes for this.

Aim: Pituitary adenomas are typically slow-growing and histologically benign tumors that can occasionally behave in a malignant-like manner, invading adjacent structures or recurring after treatment. Using protein analysis methods and multiplex xMAP assays, we aimed to find out if these particular types of tumors express angiogenic markers VEGF and basic FGF (bFGF), which are associated with tumor growth and invasiveness, and quantify them in order to establish their usefulness as biomarkers. Materials & methods: We have analysed the expression of angiogenic markers VEGF and bFGF in serum and tissue specimens from 66 pituitary adenomas (43 invasive and 23 noninvasive). For serum analysis, we used xMAP and ELISA, and for tissue analysis, we performed histopathology and immunohistochemistry. Results & conclusion: We measured the serum angiogenic factors in pituitary adenomas. The quantification methods revealed significant differences between pituitary adenoma patients and controls, for both VEGF (212.4 vs 112.5 pg/ml in controls) and bFGF (mean value of 12.6 vs 10.8 pg/ml in controls), and also differentiated between invasive and noninvasive adenomas (p < 0.05). The tissue expression of VEGF and bFGF strongly correlated with their serum level increase. Our findings can be further developed into methods for selection of patients suitable for personalized, antiangiogenic therapy.

Background. Small-cell lung carcinoma is a neuroendocrine tumor that exhibits aggressive behavior; rapid growth, early spread to distant sites and frequent association with paraneoplastic syndromes, the most frequent being the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).Case report. We present the case of a 66 year-old woman who presented to the Emergency Department for a syncope preceded by vomiting. She had one-month history of progressive confusion, disorientation, drowsiness, and generalized malaise. At presentation, the biochemical profile showed normal hemogram values, severe hyponatremia (seric sodium level 120 mg/dL), low plasma osmolality (<275 mOsm/kg). The blood tests for kidney, thyroid and adrenal functions were in normal limits. There was no evidence of congestive heart failure or nephrotic syndrome. A diagnosis of SIADH was made. Because of a high suspicion for lung cancer, chest computed tomography (CT) was done, together with neck, abdominal and pelvic CT scan, all showing normal data, excepting necrotic lymph nodes in the lower right carotid space and right paratracheal. Right laterocervical lymph node biopsy was done. The histopathological and immunohistochemical result showed lymph node metastasis of a neuroendocrine small cell carcinoma, most probably with broncho-pulmonary origin.Conclusion. The case is interesting due to long term absence of any respiratory symptom, absence of identification of pulmonary tumor, despite repeated CT scans, the only clinical manifestations being related to SIADH. Also, it emphasizes the importance of early recognition of SIADH, which may be the only initial manifestation of a neuroendocrine small cell carcinoma.

The cellular immunoprofile of cardiac dysfunctions and lesions of ischemic etiology are insufficiently studied to date, especially regarding the contribution of non-cardiomyocytic structures. Aiming to explore this immunoprofile, we used immunohistochemistry applied on embryonic, fetal and adult normal or ischemic myocardium. We observed a decrease of smooth muscle alpha-actin expression in fetal vs. embryonic cardiomyocytes, its absence in normal adult myocardium and its intense expression in the fibrotic scars of ischemic myocardium. DDR2 and vimentin, which are present in the interstitial cells and cardiomyocytes of the embryo, fetus and normal adult heart, are absent in the fibrotic scar tissue and cicatricial infarction, the latter expressing smooth muscle alpha-actin and CD34. This suggested that myofibroblasts and not local fibroblasts that participate in ischemic remodeling. An EGFR-positive vascular network was better represented in the ischemic heart than in the adult normal one, a fact possibly related to EGFR implication in cardiac ischemic pre- and post-conditioning. Therefore, cardiomyocytes and non-cardiomyocytic cells have an undulating immunoprofile according to the intrauterine life stage or age after birth, and a variable contribution in cardiac lesions, mostly in ischemic ones.