Mutations in CIC and FUBP1 Contribute to Human Oligodendroglioma

Oligodendrogliomas are the second most common malignant brain tumor in adults and exhibit characteristic losses of chromosomes 1p and 19q. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven tumors. Among other changes, we found that the CIC gene (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six cases and that the FUBP1 gene [encoding far-upstream element (FUSE) binding protein] on chromosome 1p was somatically mutated in two tumors. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.

ASPM gene expression in medulloblastoma

Medulloblastomas are the most common malignant tumors of the central nervous system in childhood. The incidence is about 19-20% between children younger than 16 years old with peak incidence between 4 and 7 years. Despite its sensibility to no specific therapeutic means like chemotherapy and radiotherapy, the treatment is very aggressive and frequently results in regression, growth deficit, and endocrine dysfunction. From this point of view, new treatment approaches are needed such as molecular targeted therapies. Studies in glioblastoma demonstrated that ASPM gene was overexpressed when compared to normal brain and ASPM inhibition by siRNA-mediated inhibits tumor cell proliferation and neural stem cell proliferation, supporting ASPM gene as a potential molecular target in glioblastoma. The aim of this work was to evaluate ASPM expression in medulloblastoma fragment samples, and to compare the results with the patient clinical features. Analysis of gene expression was performed by quantitative PCR real time using SYBR Green system in tumor samples from 37 children. The t test was used to analyze the gene expression, and Mann-Whitney test was performed to analyze the relationship between gene expressions and clinical characteristics. Kaplan-Meier test evaluated curve survival. All samples overexpressed ASPM gene more than 40-fold. However, we did not find any association between the overexpressed samples and the clinical parameters. ASPM overexpression may modify the ability of stem cells to differentiate during the development of the central nervous system, contributing to the development of medulloblastoma, a tumor of embryonic origin from cerebellar progenitor cells.

Extremely late development of pituitary carcinoma after surgery and radiotherapy

Introduction Pituitary carcinomas account for 0.1 or 0.2% of pituitary tumors. The authors report a rare case of a pituitary carcinoma mimicking a radio-induced meningioma. Case report Fifty-five years-old male presents a previous history of transcranial surgery in 1983 for invasive pituitary adenoma followed by whole-brain radiotherapy (5100 cGy). After three years he presented worsening of visual deficits and MRI evidenced recurrence of the lesion. In 1992, he underwent a transcranial approach to treat recurrent supraselar disease, followed by stereoctatic radiotherapy. In 2006, clinical condition was stable; however three right frontal extra-axial lesions were diagnosed by MRI, compatible with meningioma. The histological examination revealed pituitary adenoma. No lesions were found in craniospinal axis. Further treatment was not recommended by radiotherapists due previous actinic treatments. Two years radiological follow-up revealed no recurrence. Conclusion In these high risk cases, active and constant surveillance must be pertained, regardless the time of follow-up.

An integrated genomic analysis of human glioblastoma Multiforme

Glioblastoma multiforme ( GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high- density oligonucleotide arrays, and performed gene expression analyses using next- generation sequencing technologies in 22 human tumor samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs. Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 ( IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs.

Validation of brief pain inventory to Brazilian patients with pain

To validate the Brazilian version of the Brief Pain Inventory (BPI-B) scale and to determine the optimal cutpoints for mild, moderate, and severe pain based on patients` rating of their worst pain. One hundred forty-three outpatients with cancer were recruited in Hospital das Clinicas-University of Sao Paulo, Brazil. Confirmatory factor analysis confirmed two underlying dimensions, pain severity, and pain interference, with Cronbach`s alpha of 0.91 and 0.87, respectively. Convergent validity was shown by the correlation observed between the BPI dimensions with the EORTC-QLQ-C30 pain scale and the McGill Pain Questionnaire. The BPI-B detected significant differences in the two dimensions by disease and performance status, supporting known-group validity. For the worst pain, the optimal cutpoints were 4 and 7 (1-4 = mild pain, 5-7 = moderate, and 8-10 = severe). Our data show that BPI-B is a brief, useful, and valid tool for assessing pain and its impact on patient`s life.

The Genetic Landscape of the Childhood Cancer Medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.

Evaluation of inverted papilloma and squamous cell carcinoma by nasal contact endoscopy

Background: Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. This study described and compared the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma (SCC) and tested the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. Methods: The patients included in this study were divided into group A, patients diagnosed with inverted papilloma, and group B, patients diagnosed with SCC. CE results were compared among themselves. CE images were presented to examiners not experienced with the method. Results: Twenty-two patients were examined, 13 in group A and 9 in group B. The main relevant differences in CE findings between those two groups were corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. Conclusion: CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal SCC, which may enable better preoperative planning. (Am J Rhinol Allergy 24, 210-214, 2010; doi: 10.2500/ajra.2010.24.3467)

Hormone therapy in Brazilian postmenopausal women with chronic hepatitis C: a pilot study

Design Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 mu g estradiol plus 170 mu g norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. Results No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. Conclusions There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

Analysis of cell cycle phases and proliferative capacity in mice bearing melanoma maintained on different dietary proteins

Background Diet seems to represent, directly or indirectly, 35% of all cancer reports. In this study, the influence of dietary protein on the growth of melanoma B16F10 was evaluated through analyses of cell cycle phases and proliferative capacity. Methods Flow cytometry and argyrophilic nucleolar organizer regions (AgNORs) technique were applied in mice bearing B16F10 melanoma cells fed on different dietary proteins. All data were submitted to statistical analyses. Results The G0/G1 phase increased for the animal groups fed bovine collagen hydrolysate (BCH) or BCH-P1 + whey protein isolate (WPI), compared with mice receiving only WPI, for all dietary groups treated and nontreated with paclitaxel. Mice that received BCH + WPI treated with paclitaxel showed the highest percentage of apoptosis compared with WPI group. AgNORs, total nucleolar organizer regions (NORs)/cells and dot number/cell for all dietary protein groups nontreated with paclitaxel were higher than for the WPI. The only two dietary protein groups treated with paclitaxel that presented higher total NORs and dot number/cell than the WPI group were BCH + WPI and BCH-P1 + WPI. Conclusions A significantly lower proliferative capacity and larger number of cells in the G0/G1 phase were observed for the dietary protein groups combining the two collagen hydrolysates, BCH or BCH-P1 with WPI, treated with paclitaxel. Castro GA, Maria DA, Rodrigues CJ, Sgarbieri VC. Analysis of cell cycle phases and proliferative capacity in mice bearing melanoma maintained on different dietary proteins.

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma

Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.

Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis type: immunohistochemical evidence that they are secondary tumors

Pseudomyxoma peritonei (PMP) is a clinical condition initially thought to be related to ovarian mucinous tumors; however, immunohistochemistry and molecular biology techniques have convincingly made the link to appendiceal mucinous neoplasms, resulting in changes in histologic and clinical approaches. The objective of this study was to compare the immunohistochemical profile of ovarian tumors associated with PMP and intestinal mucinous ovarian neoplasms without PMP. The study was retrospective and included 28 intestinal ovarian mucinous tumors selected from the files of the Division of Surgical Pathology of the University of Sao Paulo Medical School, from 1996 to 2005. Seven cases were associated with PMP of disseminated peritoneal adenomucinosis-type and all presented borderline histology. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC, and MUC6), CK7, CK20, CA19.9, and CA125 were performed in tissue microarrays. Of note, we detected differences in the expression of MUC2 and CK20 between cases with and without PMP. Comparisons of borderline histology with that of benign/malignant tumors also revealed differences in MUC2 and CK20. Our results confirm that there is a distinct profile of intestinal ovarian tumors associated with pseudomyxoma, particularly with respect to the expression of the gel-forming mucin MUC2. The profile of borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type, suggesting that borderline histology may represent a secondary tumor or a less aggressive variant of PMP. An appendiceal origin seems the most probable for this group of neoplasias.

Arginase-1 A New Immunohistochemical Marker of Hepatocytes and Hepatocellular Neoplasms

The distinction of hepatocellular carcinoma (HCC) from metastatic tumor in the liver often presents a diagnostic challenge that carries significant impact on prognostication and therapy. The number of diagnostically useful immunohistochemical markers of hepatocytes is limited to hepatocyte paraffin antigen (HepPar-1), polyclonal carcinoembryonic antigen, and CD10, with alpha-fetoprotein and glypican-3 labeling HCCs. Arginase-1 (Arg-1) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of arginine to ornithine and urea. We used immunohistochemistry to compare the sensitivity of Arg-1 to that of HepPar-1 in 151 HCCs. We found that the overall sensitivities of Arg-1 and HepPar-1 are 96.0% and 84.1%, respectively. The sensitivities of Arg-1 in well, moderately, and poorly differentiated HCCs are 100%, 96.2%, and 85.7%, respectively, whereas, in comparison, HepPar-1 demonstrated sensitivities of 100%, 83.0%, and 46.4% for well, moderately, and poorly differentiated tumors, respectively. There were no HCCs in our study that were reactive for HepPar-1 but nonreactive for Arg-1. We also examined Arg-1 expression in nonhepatocellular tumors, including many that are potential mimics of HCC (renal cell carcinomas, neuroendocrine tumors, melanomas, gastric adenocarcinomas, and adrenocortical carcinomas) and found that only 2 non-HCC tumors were reactive for Arg-1. Arg-1 represents a sensitive and specific marker of benign and malignant hepatocytes that may ultimately prove to be a useful diagnostic tool in routine surgical pathology practice.

Hodgkin`s Lymphoma Presenting as Dominant Gastric Lesion in Immunocompetent Patients: Report of 5 Cases With EBV Analysis

Primary Hodgkin`s lymphoma (HL) of the stomach is an extremely rare entity. Most cases of gastric involvement by HL are observed in the setting of disseminated disease. The nonspecific nature of the symptoms and endoscopic findings, which include a large malignant-looking ulcer and mass or wall thickening, together with the considerable histological overlap between HLs and some non-HLs or undifferentiated carcinoma, make the surgical resection diagnosis extremely difficult. An accurate diagnosis is important as treatment and outcome differ significantly for these neoplasms. In small endoscopic gastric biopsies and even in postoperative specimens, the precise histological diagnosis of HL is particularly challenging. Here, the authors report 5 cases of 2 women and 3 men aged 22 to 68, with gastric involvement by classic HLs-3 primary gastric HLs and 2 as part of widespread disease. All 5 patients presented with digestive symptoms. At endoscopy, the lesions presented as ulcerated and elevated lesions, with or without mucosal thickening. Four patients were misdiagnosed in the preoperative biopsy or in the gastrectomy specimen. Association with Epstein-Barr virus (EBV) was detected in 4 cases, with a predominance of subtype A EBV. These cases illustrate the significant difficulties, both clinical and pathological, in achieving the diagnosis of HL involving the stomach in immunocompetent patients.

Multiple epidural haematomas after meningioma surgery

Intracranial meningioma removal carries a higher risk of post-operative haemorrhage compared with other intracranial neoplasm surgeries. We report a patient who developed three intracranial haematomas following a frontal meningioma removal.

Chondrosarcoma of Bone Lessons From 46 Operated Cases in a Single Institution

Background Bone chondrosarcomas are rare malignant tumors that have variable biologic behavior, and their treatment is controversial. For low-grade tumors, there is no consensus on whether intralesional en bloc resections are the best treatment. Questions/purposes We therefore compared patients with Grade 1 and Grade 2 primary central chondrosarcomas to (1) determine difference in survival and (2) local recurrence rates; and (3) determine any association of histological grade with some clinical and demographic characteristics. Methods We retrospectively reviewed 46 patients with grade 1 and 2 chondrosarcomas. There were 25 men and 21 women with a mean age of 43 years (range, 17-79 years). Minimum followup was 32 months (mean, 99 months; range, 32-312 months) for the patients who remained alive in the end of the study. Twenty-three of the tumors were intracompartmental (Enneking A); of these, 19 were Grade 1 and 4 were Grade 2. Twenty-three tumors were extracompartmental (Enneking B); of these, 4 were Grade 1 and 19 were Grade 2. Twenty-five patients underwent intralesional resection, 18 had wide resection, and three had amputations. Results The overall survival rate was 94% and the disease-free survival rate was 90%. Among the 23 Grade 1 tumors, we observed six local recurrences and none of these patients died; among the 23 Grade 2 tumors, 10 recurred and two patients died. Local recurrence negatively influenced survival. Conclusions For lesions with radiographic characteristics of intracompartmental Grade 1 chondrosarcoma, we believe intralesional resection followed by electrocauterization and cement is the best treatment. When the imaging suggests aggressive (Grade 2 or 3) chondrosarcoma, then wide resection is promptly indicated.