BACKGROUND: Neoplasms located in the Meckel cave account for 0.2% -0.5% of all intracranial tumors. This area is the site of many types of pathologic lesions, most often trigeminal nerve schwannomas and meningiomas. Melanin-containing tumors are rare in this area. These tumor types can be suspected if the magnetic resonance characteristics of a tumor has some differences in comparison with other types of central nervous system neoplasms. In fact, differential diagnosis of melanotic tumors is based mainly on the histopathologic criteria and immunohistochemical profile. This article presents a case report of melanotic schwannoma of the Meckel cave and a literature review of the problem. CASE DESCRIPTION: A 23-year-old man underwent a 2-stage surgery for a dumbbell pigmented mass lesion located in the Meckel cave. No signs of recurrence were seen on follow-up magnetic resonance imaging (MRI) 3.5 years after the operation. CONCLUSIONS: Melanin-containing tumor can be suspected in the presence of radiologic characteristics, such as a hyperintense MRI signal on T1-weighted images and a hypointense signal on T2-weighted images. If a black extracerebral tumor is detected, the main course of surgical treatment is maximal excision despite it possibly being a malignant melanoma and the temptation to perform partial resection because of an unfavorable prognosis. Chemotherapy can be justified in the presence of an aggressive melanotic schwannoma.

Primary extraspinal myxopapillary ependymoma (MPE) is an exceptionally rare lesion that is mainly located in the subcutaneous sacrococcygeal region. We describe the first case of MPE that presented as an intramuscular tumor mass located in the lumbar area. Absence of the visible connection with the spinal cord and lack of any other tumors in the reported case argue for the primary ectopic origin of the MPE. The differential diagnosis of MPE is discussed. Additionally, we evaluated the expression level of molecular biomarkers that have a prognostic value in central nervous system tumors.

Background: A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk. Methods: The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed. Published: 25 February 2009 Hereditary Cancer in Clinical Practice 2009, 7:5 doi:10.1186/1897-4287-7-5 Received: 8 November 2008 Accepted: 25 February 2009 This article is available from: http://www.hccpjournal.com/content/7/1/5 © 2009 Suspitsin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Breast carcinomas caused by inheritance of cancer-predisposing germ-line mutations have specific bioclinical features. This study aimed to analyze the efficacy of conventional cytotoxic treatment in BRCA1 and CHEK2 mutation carriers and non-carriers. The study included 415 Russian breast cancer patients aged 50 years or younger, who were subjected to various standard schemes of neoadjuvant therapy. The choice of therapy was done without the knowledge of the mutations status, because DNA testing was performed retrospectively using the archival tissue samples. 19 BRCA1 (4.6%) and 8 CHEK2 (1.9%) heterozygous genotypes were identified. BRCA1 mutation carriers achieved pathological complete response more frequently than non-carriers [6/19 (31.6%) vs. 46/388 (11.9%), p = 0.024]; this effect was limited to women treated by anthracycline-based therapy without taxanes [5/9 (55.6%) vs. 28/247 (11.3%), p = 0.002] and was not observed in any of 7 BRCA1 carriers receiving taxane-containing regimens. CHEK2 heterozygotes did not experience pathological complete response and showed lower frequency of objective clinical responses as compared to mutation non-carriers [4/8 (50%) vs. 333/388 (85.5%), p = 0.020]; the efficacy of neoadjuvant therapy was particularly poor in CHEK2 carriers receiving anthracyclines without taxanes. This study provides evidence for distinct sensitivity of BRCA1 and CHEK2 mutation-driven breast carcinomas to standard chemotherapeutic schemes.

Results of molecular genetic study of BRCA1gene expression in patients with endocrine tumors of the gastrointestinal tract were presented. Based on the analysis of survival rates in patients with endocrine tumors of the gastrointestinal tract, the BRCA1expression level was suggested can be used as a prognostic criterion and as a factor determining the advisability of administration of platinum-based drugs. It was found that the more aggressive neuroendocrine tumors had the lower BRCA1expression. Therefore, administration of platinumcontaining chemotherapy is unlikely to offer any benefit for these patients.

ABSTRACT Background TURANDOT is the first prospective trial to compare BEV combined with either paclitaxel (PAC) or capecitabine (CAP). We report the planned interim analysis (IA) of efficacy. Methods Patients with HER2-negative mBC who had received no prior chemotherapy for mBC were randomised to receive either BEV–PAC (BEV 10 mg/kg d1 & 15 + PAC 90 mg/m d1, 8 & 15 q4w) or BEV–CAP (BEV 15 mg/kg d1 + CAP 1000 mg/m bid d1–14 q3w) until disease progression or unacceptable toxicity. The primary objective is to demonstrate non-inferior overall survival (OS) with BEV–CAP vs BEV–PAC. Interim and final OS analyses were planned after 175 and 389 deaths, respectively, in the per-protocol (PP) population to reject the null hypothesis of inferiority (hazard ratio [HR] ≥1.33) with 80% power and overall α = 0.025. Secondary endpoints include response rate (RR), progression-free survival (PFS), safety and quality of life. Results Median follow-up was 19 months at data cut-off for this IA (1 Sep 2011). Baseline characteristics were generally similar in the 2 treatment arms. BEV-PAC (n = 285) BEV–CAP (n = 279) Median age, years 59 59 Visceral metastases, % 65 73 Prior (neo)adjuvant taxane, % 20 18 OS a Events, % 33 35 1-year OS rate, % b 81 79 HR (97.5% RCI c ) for non-inferiority 1.04 (-∞ to 1.69) p = 0.0593 d RR Overall, % 44 27 CMH test (superiority) p  PFS Events, % 62 77 Median, months 11.0 8.1 HR (95% CI) 1.36 (1.09 to 1.68) Log-rank (superiority) p = 0.0052 RCI = repeated confidence interval a PP population (n = 533) b Kaplan–Meier estimate c Using O'Brien–Fleming boundaries d Non-inferiority not shown as p > 0.00105 (α at IA) AEs were consistent with the known safety profiles of BEV, PAC and CAP. The most common grade ≥3 AEs were neutropenia (18%), peripheral neuropathy (14%) and leucopenia (7%) with BEV–PAC and hand-foot syndrome (16%), hypertension (6%) and diarrhoea (5%) with BEV–CAP. Conclusion In this planned IA, the non-inferiority criterion has not been met but OS results do not indicate relevant differences. Final results are expected in 2014. PFS and RR were better with BEV–PAC and very similar to previous data for BEV–PAC (E2100) and BEV–CAP (RIBBON-1). Disclosure R. Greil: RG has received research support and honoraria from Roche. S. Beslija: SB has received research support and honoraria from Roche. D. Messinger: Employee of IST GmbH, CRO which is providing various services and consultancies for Hoffmann-La Roche and CECOG. T. Brodowicz: TB has received honoraria from Roche. All other authors have declared no conflicts of interest.

Drug treatment of disseminated non small cell lung cancer (NSCLC) is an actual issue today. Both clinical and economic efficacy analysis is needed for optimal therapy selection. We performed economic efficacy assessment of gefitinib (G.) therapy in patients with non operable NSCLC who hase no EGFR mutation using Markov model based on results of clinical studies conducted in N.N. Petrov Research Institute of Oncology. G. increases overall survival of patients with NSCLC with EGFR mutation by 1,05 year. Cost/efficacy coefficient for G. in patients with EGFR mutation is 934 800 rub per 1 acquired year of life. Therapy with G just for patients with genetically proven mutation is dominating strategy when compared to therapy for all NSCLC patients irrespectively to mutation status (saving 211600 – 251800 rub per 1 patient taking into account equal clinical efficacy). Therapy with G. is economically justifying strategy when compared to chemotherapy (additional costs coefficient 960700 – 1010000 rub per 1 gained year of life). Thus, EGFR mutation testing with subsequent G. therapy in non operable NSCLC patients not only prolongs patient’s life but also has acceptable level of medical expenses.

ABSTRACT Background The highest synergism of G was registered with C, as G suppresses DNA reparation after its damage from C, which leads to apoptosis of tumor cell. The study of optimal doses of G and C combination continues for intensive pretreated MBC. Purpose Evaluate efficiency and tolerability of the low doses of G and C in 131 patients with MBC progressing after anthracyclines, taxanes, capecitabine and other antineoplastic agents. Methods G 600-750 mg/m2 and C 30 mg/m2 were administered on days 1 and 8 every 3 weeks in the 2nd line for 28 patients, in the 3rd for 54 patients and in the 4th for 49 patients. Groups were comparable in age, performance status (PS), ER/PgR and HER2 expressions, localization and number of metastatic sites prior to treatment. Results Total amount of cycles: 549, median 4.2 per patient (range: 2-12). The overall response (OR) of all patients was 27%, clinical benefit (OR + stable disease) – 71.7%, with median time to progression (TTP) 4.8 months (95% CI 3.9-5.7 months) and median overall survival (OS) 14.6 months (95% CI 12.1-17.1 months). The OR in the 2nd line was observed in 39.3%, in the 3rd – 27.8% and in the 4th– 18.4% (р 0.05) respectively. Pain intensity reduction and improvement of PS were noted in patients in spite of the lines. Linear discriminant and regression analyses showed that OR, TTP and OS didn't depend on the ER/PgR and HER2 expressions, but ECOG 2-3, pain syndrome, metastases in the lymph nodes and liver were the factors of poor prognosis. The treatment-related adverse events were neutropenia, anemia, thrombocytopenia, alopecia, nausea, vomiting, peripheral neuropathy and fatigue. Toxicities with grade 3-4 intensity were neutropenia (31.6% of patients), vomiting (0.8%), anemia (2.3%), thrombocytopenia (3.1%). No febrile neutropenia and deaths related to the study treatment occurred. Conclusions The low doses of G with C are effective and tolerable in treatment of MBC progressing after antracycline, taxanes, capecitabine, other antineoplastic agents not only in the 2ndand 3rd, but also in the 4th lines and are suitable for outpatient therapy. Disclosure All authors have declared no conflicts of interest.

The BLM gene belongs to the RecQ helicase family and has been implicated in the maintenance of genomic stability. Its homozygous germline inactivation causes Bloom syndrome, a severe genetic disorder characterized by growth retardation, impaired fertility and highly elevated cancer risk. We hypothesized that BLM is a candidate gene for breast cancer (BC) predisposition. Sequencing of its entire coding region in 95 genetically enriched Russian BC patients identified two heterozygous carriers of the c.1642 C>T (Q548X) mutation. The extended study revealed this allele in 17/1,498 (1.1%) BC cases vs. 2/1,093 (0.2%) healthy women (p = 0.004). There was a suggestion that BLM mutations were more common in patients reporting first-degree family history of BC (6/251 (2.4%) vs. 11/1,247 (0.9%), p = 0.05), early-onset cases (12/762 (1.6%) vs. 5/736 (0.7%), p = 0.14) and women with bilateral appearance of the disease (2/122 (1.6%) vs. 15/1376 (1.1%), p = 0.64). None of the BLM-associated BC exhibited somatic loss of heterozygosity at the BLM gene locus. This study demonstrates that BLM Q548X allele is recurrent in Slavic subjects and may be associated with BC risk.

A single institution series of 48 mucosal melanomas (MMs) has been analyzed for the presence of KIT mutations using high-resolution melting and sequencing of abnormally melted DNA fragments. The analysis of exons 9, 11, 13, and 17 has revealed eight of 48 (17%) nonsynonymous alterations, including zero of seven head and neck, six of 24 anorectal, one of 15 genitourinary, one of one gastric, and zero of one mediastinal MMs. Seven of these mutations were potentially associated with the tumor sensitivity to KIT tyrosine kinase inhibitors. One tumor harbored somatically acquired silent nucleotide substitution c.1383A>G (T461T). This study adds to the evidence that a substantial portion of MMs carry a therapeutically relevant mutation in the KIT oncogene.

This case report describes a 35-year-old woman who was diagnosed with mixed epithelial/mesenchymal metaplastic carcinoma (carcinosarcoma) of the breast. Genetic analysis of blood DNA revealed a common founder mutation, BRCA1 5382insC. Examination of microdissected tumor samples determined that both epithelial and mesenchymal components contained deletion of the wild-type BRCA1 allele. This report exemplifies that even very uncommon breast tumor types may develop through biallelic inactivation of BRCA1 gene, that has to be considered in the genetic testing settings.

© 2011 S. Karger GmbH, Freiburg Verlag, Herausgeber, Redaktion und Verlagsgeschäftsführung übernehmen keine Verantwortung für den Inhalt dieser Rubrik. In der Behandlung der chronischen Immunthrombozytopenie (ITP) hat sich ein grundlegender Wandel vollzogen. Nicht zuletzt die Einführung von Romiplostim (Nplate®) als erster Thrombopoetin-Rezeptor-Agonist brachte es mit sich, dass die bisherigen Therapieempfehlungen überarbeitet werden mussten. Über die nationale ITP-Leitlinie äußert sich der federführende Autor, Prof. Dr. Axel Matzdorff, Saarbrücken, im Gespräch mit der Medizinjournalistin Marianne E. Tippmann.

was obtained by bronchoscopy, and the morphological analysis classified the tumor as adenocarcinoma. A subsequent EGFR mutation test revealed a canonical TKI-sensitizing deletion located within exon 19 of the gene. Given the poor performance status of the patient, the extensive local tumor spread and the presence of a highly predictive EGFR mutation, immediate surgical intervention was considered unreasonable. Instead, neoadjuvant therapy with gefitinib (250 mg daily) was initiated. In addition, hemostatic treatment with etamsylate (250 mg by intramuscular injection, 3 times daily) was performed for 3 days. The prescribed therapy led to rapid symptomatic relief: by day 4, the ECOG status reached 1, and no signs of hemoptysis or paraneoplastic edema were observed. X-ray and CT examinations were repeated on day 12 of gefitinib therapy. A dramatic reduction of the primary tumor and hilar lymph nodes as well as disappearance of the bifurcational lesions were detected (fig. 1); given the significant downstaging of the disease and good performance status of the patient, a right pneumonectomy with systematic ipsilateral mediastinal lymph node dissection was performed 2 days later. Both preand post-treatment tissue samples contained a sufficient number of neoplastic cells, therefore it was possible to microdissect tumor tissues, isolate RNA, and perform reverse transcription polymerase chain reaction (RT-PCR) expression analysis of a few candidate genes. In addition to the above mentioned EGFR-inducible inflammatory molecules (IL6, IL8, ICAM1), we also considered the TNF-alpha and IL1-beta genes. Both these cytokines contribute to the mobilization of immune cells. TNF-alpha is involved in the formation of peritumoral pleural effusion [7]. A specific haplotype of the IL1-beta was shown to be associated with increased gene expression and elevated lung cancer risk [8]. As a control, we deliberately included in the study 2 genes, which are not related to inflammatory reactions, DPD and ERCC1.

1), tables as (table 1).Data already mentioned in the text need not be repeated in a table.Accordingly, numbers used in tables need not be repeated in the text.For the reproduction of illustrations, only good drawings and original photographs can be accepted.

Background: Several Asian studies demonstrated feasibility of front-line administration of gefitinib for the treatment of non-small cell lung carcinomas (NSCLCs) harboring intragenic epidermal growth factor receptor (EGFR) mutations. The experience of the use of this EGFR tyrosine kinase inhibitor (TKI) in non-Asian subjects remains limited. Patients and Methods: The study included lung adenocarcinoma (AC) patients treated at the N.N. Petrov Institute of Oncology (Russia). Results: DNA analysis of 192 consecutive AC revealed 38 (20%) TKI-sensitizing mutations. Presence of the exon 19 deletion (del19) or L858R was strongly correlated with nonsmoking status (smokers: 8/98 (8%); non-smokers: 30/94 (32%); p = 0.00004). The efficacy of first-line gefitinib therapy was evaluated in 25 patients with EGFR-mutated advanced AC. Twelve (48%) cases demonstrated tumor response (1 (4%) complete response, 11 (44%) partial responses; 10/17 (59%) patients with del19 mutation vs. 2/8 (25%) cases with L858R substitution, p = 0.11). The remaining 13 (52%) patients experienced disease stabilization. Median progression-free survival was 8.0 months. Grade 3 toxicity was the maximal adverse event, being observed only in 4 (16%) cases. Conclusion: Gefitinib may be considered as an upfront treatment option for EGFR-mutated NSCLC.