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A rare case of malignant mesothelioma in a 15-year-old girl is described. The patient presented with secondary amenorrhoea and clinical symptoms resembling those of an ovarian cyst. One large and multiple small peritoneal nodules were found at laparoscopy. Histologically the tumour was characterised by an unusual pattern with a superficial resemblance to decidual reaction, but because of significant mitotic activity the diagnosis of a malignant tumour, epithelial mesothelioma with deciduoid features, was made. The patient died 11 months after diagnosis. Post-mortem examination revealed extensive extraperitoneal spread. [ABSTRACT FROM AUTHOR]

The influence of the treatment schedule of dianhydrogalactitol on its effect on the activity of mucosal enzymes in rat intestine was studied. The effect of a single high dose (10 mg/kg) was compared with that of repeated small doses (4 x 2.5 mg/kg) given at daily intervals. At 48 h after a single high dose the activities of thymidine kinase, which is a marker of dividing crypt cells, and of alkaline phosphatase, sucrase, maltase, xanthine oxidase, which are markers of mature enterocytes, were strongly depressed. Even 96 h after the treatment low enzyme activities could be observed. Repeated small doses caused milder enzyme inhibition and almost total recovery had occurred by 96 h after administration of the last dose. The results indicate that fractionation of drug administration can reduce the toxic side-effects on the intestinal mucosa and might be partly responsible for the higher therapeutic index of such schedules in experimental tumor models. [ABSTRACT FROM AUTHOR]

Objective: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT tyrosine kinase receptor that is potential therapeutic targets for imatinib mesylate indicating that molecular diagnostics has important role in clinical practice. Here we report our experience with a PCR and capillary gel electophoresis-based mutational analysis of KIT gene in clinical samples of GISTs. Methods: For this study, 58 tumor blocks were selected and mutational analysis in exons 9 and 11 was performed using PCR amplification of target exons of KIT followed by the Agilent 2100 bioanalyzer aided visualization. The results were validated by direct sequencing. Results: We detected KIT exon 11 mutation in 39 of 58 cases (67.2%) and exon 9 mutation in 4 of 53 cases (7.5%). The results corresponded perfectly to sequencing data of normal and mutant tissues except in one case, where we can not able to detect mutation, whereas homozygous mutation was present. Conclusions: Heterozygous mutations can be resolved accurately. The method described here seems to be rapid and accurate screening assay completed the sequencing. [ABSTRACT FROM AUTHOR]

Objective: We tried to correlate the clinico-pathologically features of colorectal cancer (CRC) to expression of eight immunohistochemically (IHC) markers and microsatellite instability (MSI) in order to realyze a molecular subdivision of these tumors. Methods: 300 CRC, surgical specimens, were statistically and IHC evaluated. MSI status was analyzed in 52 cases, with Real Time PCR, melting point analysis. The following IHC markers have been used: CD8, E-cadherin, HER-2, p53, Ki67, bcl-2, MLH-1, CEA. The molecular phenotypes have been reported to the node status (pN) and MSI. Results: Based on statistically analyses, we revealed that CEA and Ki67 were not prognostic factors. MLH-1 may indicate the MSI status and the number of tumor inflitrated lymphocytes stained with CD8 seems to be higher in the MSI cases and tumors of the proximal colon. HER-2 expression was correlated to number of the lymph node metastatses and bcl-2 was negative is most of the CRC diagnosed in advanced stages. Conclusions: The CRC may be subdivided in six molecular prognostic groups, the best prognosis showing the MSI/p53-/bcl-2+/HER-2- and the worst MSS/p53+/bcl-2±/HER-2+. These molecular subdivision may be the basis for targeted therapy in node negative CRC. [ABSTRACT FROM AUTHOR]

Objective: Approximately 20% of colorectal adenocarcinomas are characterized by high microsatellite instability. Tumors showing high level of microsatellite instability (MSI) have a typical histology, age distribution, and it may affect both the course of the disease and - consequently - the required cancer therapy. The article offers certain practical aspects related to the introduction of molecular biological and histological features in routine diagnostic practice that may facilitate the identification and the efficient treatment of microsatellite unstable colorectal carcinomas. Our aim was to review the literature of MSI and to summarize our practical findings in the detection of MSI and BRAF mutation in colorectal cancer. Methods: From the register of the National Institute of Oncology we tested 387 cases of colorectal cancer, where the clinical stage and the microsatellite status were also taken into account. DNA was isolated from formalin-fixed and paraffin embedded tissues of these tumors, BRAF mutational analysis and MSI status analysis were performed using real time polymerase chain reaction followed by melting curve analysis. Results: We have found 42 hereditary non-polyposis colorectal carcinomas (HNPCC) and 32 sporadic MSI-H (high frequency microsatellite instability) carcinomas among these 387 cases. MSI-H colon cancers showed typical age distribution and histological picture. The differences between the HNPCC and sporadic MSI-H colon cancers were the age distribution, localization and the BRAF mutation status. The microsatellite stable cancers completely differed from MSI-H tumors in morphological features, age distribution, localization and clinical stage at the time of primary tumor recognition. Conclusion: Our data can help to recognize microsatellite instable colorectal carcinomas and provide relevant information to select most appropriate treatment. [ABSTRACT FROM AUTHOR]