[Practical approach to molecular pathology of central nervous system tumours]. / A központi idegrendszeri daganatok molekuláris patológiája gyakorlati szempontból.

Recent advances in molecular diagnostics are transforming the classification of malignant tumours, it has long played a major role in the field of CNS tumours. Examination of 1p/19q codeletion is indispensable in case of diffuse gliomas. Glioblastoma may be diagnosed even in the absence of characteristic morphological features, when EGFR amplification, TERT promoter mutation or +7/-10 copy number abnormalities are present. The number of entities defined by a genetic abnormality is growing. Comprehensive analysis of DNA methylation may be of considerable help in addition to histology and basic molecular studies, especially in case of small samples. Keeping up with the ever-expanding diagnostic repertoire is difficult, however, advantages and disadvantages of these methods and the context in which they may be useful should be understood by those who are involved in the diagnosis of CNS tumours. This summary provides a general overview of the main methods used in molecular diagnostics.

Effectiveness of four topical treatment methods in a rat model of superficial partial-thickness burn injury: the advantages of combining zinc-hyaluronan gel with silver foam dressing.

BACKGROUND: There are several options available for conservative treatment of partial-thickness burns, however, reliable, affordable, and easily obtainable animal testing models are hard to find for the comparison of the different treatment methods. We aimed at developing a preclinical testing model and at comparing four treatment methods for superficial partial-thickness burns. METHODS: Burn injury was induced in 90 adult male Wistar rats by placing the 130°C hot tip of a commercially obtainable soldering device for 30 s on the clipped skin of the interscapular region at a steady pressure. Skin histology was studied on days 5, 10, and 22 after the induction of the burn injury, on which days, respectively, the ratio of the not epithelialized wound (%), the extent of re-epithelialization (score), and the scar thickness (µm) were assessed. We compared 4 groups: silver-sulfadiazine cream, zinc-hyaluronan gel, silver foam dressing, and the combination of zinc-hyaluronan gel with a silver foam dressing. RESULTS: On day 5, the induction of superficial partial-thickness burn injury was confirmed histologically in the rats. The zinc-hyaluronan gel and the combination treatment resulted in a markedly smaller ratio of the non-epithelialized area (29 ± 10% and 28 ± 13%, respectively) than silver-sulfadiazine cream (69 ± 4%; p < 0.01). On day 10, the extent of re-epithelialization was the lowest (∼0.2) in the silver-sulfadiazine cream group, while the other 3 treatments performed significantly better. The combination treatment lead to the maximal score of 2 in all rats, which was higher than in the other 3 treatment groups. On day 22, the scar thickness was the smallest in the combination treatment group (560 ± 42 µm), which was significantly less than in the silver-sulfadiazine cream group (712 ± 38 µm; p < 0.05). CONCLUSIONS: We designed and histologically confirmed a reproducible method for induction of superficial partial-thickness burns in rats for preclinical testing. In our model, the combination of zinc-hyaluronan gel with silver foam dressing was more effective than either of its components alone or than silver-sulfadiazine cream.

Calreticulin mutation specific CAL2 immunohistochemistry accurately identifies rare calreticulin mutations in myeloproliferative neoplasms.

Mutations of the multifunctional protein calreticulin (CALR) are recognised as one of the main driver alterations involved in the pathogenesis of Philadelphia negative myeloproliferative neoplasms (Ph- MPN) and also represent a major diagnostic criterion in the most recent World Health Organization classification of myeloid neoplasms. Nowadays, quantitative assessment of the driver mutations is gaining importance, as recent studies demonstrated the clinical relevance of the mutation load reflecting the size of the mutant clone. Here, we performed for the first time a manual and automated quantitative assessment of the CALR mutation load at protein level using CAL2, a recently developed CALR mutation specific monoclonal antibody, on a cohort of 117 patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) and compared the CALR protein mutation loads with the CALR mutation load values established by a molecular assay. Eighteen different CALR mutations were detected in the cohort of the 91 CALR mutant cases. Mutation loads of the CALR mutations were between 13% and 94% with mean value in PMF cases significantly higher than ET cases (49.94 vs 41.09; t-test, p=0.004). Cases without CALR mutation (n=26) showed no or only minimal labelling with the CAL2 antibody, while all 18 different types of CALR mutations were associated with CAL2 labelling. The CALR mutation load showed a significant correlation (p=0.03) with the occurrence of major thrombotic events, with higher mutation load in patients presenting with these complications. We report a 100% concordance between the mutation status determined by immunohistochemistry and the CALR molecular assay, and we extend the applicability of this approach to 16 rare CALR mutations previously not analysed at protein level.