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Context.--NRAS is a member of the RAS family oncoproteins implicated in cancer. Gain-of-function NRAS mutations were reported in a subset of colorectal cancers. These mutations occur at codons 12, 13, and 61 and are detected by molecular genetic testing. Recently, an antibody (clone SP174) became available to immunohistochemically pinpoint NRAS Q61R mutant protein. In malignant melanoma, NRAS Q61R mutant-specific immunohistochemistry was shown to be a valuable supplement to traditional genetic testing. Objective.--To evaluate the significance of NRAS Q61R mutant-specific immunohistochemistry in a cohort of colorectal carcinomas. Design.--A total of 1185 colorectal carcinomas were immunohistochemically evaluated with SP174 antibody. NRAS Q61R mutant-specific immunohistochemistry was validated by molecular genetic testing including Sanger sequencing, quantitative polymerase chain reaction (qPCR), and next-generation sequencing. Results.--Twelve tumors showed strong SP174 immuno-reactivity. Sanger sequencing detected an identical c.182A>G substitution, causing NRAS Q61R mutation at the protein level, only in 8 SP174-positive cases. These results were confirmed by qPCR study. Subsequently, NRAS wild-type tumors with strong SP174 staining were evaluated by next-generation sequencing and revealed KRAS c.182A>G substitutions predicted to cause KRAS Q61R mutation. Review of colorectal carcinomas with known KRAS and NRAS genotype revealed that none of 62 wild-type tumors or 47 mutants other than Q61R were SP174 positive. Conclusion.--SP174 immunohistochemistry allows sensitive detection of NRAS and KRAS Q61R mutants. However, molecular genetic testing is necessary to determine specifically which RAS gene is mutated. (Arch Pathol Lab Med. 2017; 141:564-568; doi: 10.5858/arpa.2016-0147-OA), The RAS proto-oncogenes (ERAS, KRAS, and NRAS) encode HRAS, KRAS 4A, KRAS 4B, and NRAS, 4 distinct but closely related and highly homologous proteins. These enzymes, located on the inner [...]

Abstract Background Lung cancer diagnosis in tissue material with commonly used histological techniques is sometimes inconvenient and in a number of cases leads to ambiguous conclusions. Frequently advanced immunostaining techniques have to be employed, yet they are both time consuming and limited. In this study a proteomic approach is presented which may help provide unambiguous pathologic diagnosis of tissue material. Methods Lung tissue material found to be pathologically changed was prepared to isolate proteome with fast and non selective procedure. Isolated peptides and proteins in ranging from 3.5 to 20 kDa were analysed directly using high resolution mass spectrometer (MALDI-TOF/TOF) with sinapic acid as a matrix. Recorded complex spectra of a single run were then analyzed with multivariate statistical analysis algorithms (principle component analysis, classification methods). In the applied protocol we focused on obtaining the spectra richest in protein signals constituting a pattern of change within the sample containing detailed information about its protein composition. Advanced statistical methods were to indicate differences between examined groups. Results Obtained results indicate changes in proteome profiles of changed tissues in comparison to physiologically unchanged material (control group) which were reflected in the result of principle component analysis (PCA). Points representing spectra of control group were located in different areas of multidimensional space and were less diffused in comparison to cancer tissues. Three different classification algorithms showed recognition capability of 100% regarding classification of examined material into an appropriate group. Conclusion The application of the presented protocol and method enabled finding pathological changes in tissue material regardless of localization and size of abnormalities in the sample volume. Proteomic profile as a complex, rich in signals spectrum of proteins can be expressed as a single point in multidimensional space and than analysed using advanced statistical methods. This approach seems to provide more precise information about a pathology and may be considered in futer evaluation of biomarkers for clinical applications in different pathology. Multiparameter statistical methods may be helpful in elucidation of newly expressed sensitive biomarkers defined as many factors "in one point".

Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co‐stimulatory role in promoting T‐cell expansion and differentiation through the NFκB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well‐characterised primary diffuse MPM tumours including epithelioid (n = 145), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD‐1), and FOXP3 expression. Twenty per cent (34/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70‐expressing tumour cells (p < 0.01). Patients with MPM containing a higher number of CD3+ (p < 0.01), CD4+ (p < 0.01), CD8+ (p < 0.01), or FOXP3+ (p < 0.01) tumour‐infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25; p = 0.010], higher FOXP3+ TILs (HR 2.81; p = 0.004), and higher CD3+ TIL accumulation (HR 6.12; p < 0.001). In contrast, as a potential independent favourable factor, higher CD27+ TIL accumulation (HR 0.48; p = 0.037) was identified. In vitro experiments and an immunodeficient mouse model revealed that CD70 enhances the invasiveness of MPM cells through MET–ERK axis activation. Further analyses in syngeneic mouse models demonstrated possible roles for CD70 in immune evasion. Collectively, these findings suggest that the CD70–CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti‐tumor immune response in patients with these neoplasms. These markers might be useful in MPM for prognostic evaluations as well as targeted therapeutics. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The first aim of our study was to examine the association between common variants in VDR [rs2228570 ( FokI), rs1544410 ( BsmI), rs7975232 ( ApaI), rs731236 ( TaqI) and rs11568820 ( Cdx2)] and lung cancer risk in the Polish population. Genotyping and statistical analysis which included Chi-square test with Yates correction and haplotype frequency analysis were performed on a series of 840 consecutively collected lung cancer patients and 920 healthy controls. The second aim was to evaluate the link between serum 25(OH)D concentration and the number of lung cancers in a subgroup of 200 patients. A separate control group that consisted of 400 matched (by age, sex, smoking habits and the season of blood collection) healthy individuals was used to avoid posterior adjustment on the matched variables. Statistical analysis with the use of Chi-square test with Yates was performed. We found no statistically significant difference in the distribution of the allels of studied VDR variants among cases and controls. A statistically significant over-representation of VDR haplotypes: rs731236_A + rs1544410_T [odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.11-5.32, p < 0.001], rs731236_G + rs1544410_T (OR = 1.54, 95% CI = 1.31-1.81, p < 0.001) and rs731236_G + rs1544410_C (OR = 0.04, 95% CI = 0.03-0.07, p < 0.001) was detected. We found a tendency toward an increased number of lung cancers among individuals with low serum levels of 25(OH)D. To answer the question, whether VDR can be regarded as lung cancer susceptibility gene and low 25(OH)D serum levels is associated with lung cancer occurrences, additional, multicenter study needs to be performed. [ABSTRACT FROM AUTHOR]

Presents information which relates to a case report on the intentional intoxication with natural hallucinogenic substances with reference to hallucinogenic mushroom which is a major problem in the United States and Europe. Reference to the case of a 18-year-old man who contracted several aliments from the ingestion of this mushroom; Description of Psilocybe intoxications; Discussion on the predicted risks of indole concentrations of the mushroom.

European countries. The important source of those psychodysleptics may be a spreading growth of Psilocybe genus mushrooms. Material and Methods: To verify a previously published hypothesis on cardiotoxicity of hallucinogens, the experimental study in the form of a three-month test on male Wistar rats was performed. The study groups received intraperitoneally psilocin (PSI) in a dose of 10 μg/kg body weight (b.w.) or beta-phenylethylamine (PEA) in a dose of 1 mg/kg b.w. dissolved in 5% ethanol every second day for 2 and 12 weeks. The control groups received 5% ethanol or 0.9% solution of NaCl for the same time periods. At the end of the experiment, biochemical blood parameters, ECG, and myocardial energetic status were examined, as well as histopathological and electron-microscopic examinations were performed. The decreased serum magnesium concentrations in the PSIexposed animals were noted. Results: The obtained results showed that the repeated (12 weeks) administration of PSI produces in rats ECG abnormalities in the form of tachycardia, myocardial ischaemia and aberrant intraventricular conduction. It was also stated that long-term exposure to PSI and PEA exerts a crucial effect on the energy heart muscle metabolism, which has been reflected in the complex changes in the myocardial profile of purine concentrations. These abnormalities corresponded with degenerative changes in cardiomyocyte mitochondria observed on histopathological and electron microscopy examinations. Conclusions: The results of the study indicated a cardiotoxic effect of psilocin, manifested by functional and structural changes in cardiomyocytes and coronary arteries. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to compare the metabolic response in the early postoperative period after radical resection of stage I and II oesophageal cancer applying a minimally invasive procedure and an open procedure involving classical laparotomy and thoracotomy., Material and Methods: Serum concentrations of interleukin 6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and total serum protein (TP) and leukocyte count (WBC) in blood collected on the day of surgery prior to the procedure (day 0) and on days 1, 2 and 7 after the surgery were measured in two groups of patients undergoing oesophageal resection due to cancer: applying a minimally invasive procedure involving laparoscopy and videothoracoscopy (group A) and applying a classical procedure involving full opening of the chest and abdominal cavity (group B). The study involved a total of 24 patients divided into two groups of 12 patients each., Results: Tumour necrosis factor-α concentration was lower in group A compared to group B on day 0, PCT concentration was lower in group A compared to group B on day 2 after surgery, and on the remaining days TNF-α and PCT concentrations were not statistically different between groups., Conclusions: Lower concentration of PCT on post-surgery day 2 in the group of patients undergoing minimally invasive oesophageal resection seems to be associated with a smaller perioperative injury. Lower TNF-α concentration in serum collected on day 0 in the group of patients undergoing minimally invasive resection is associated with a lower stage of oesophageal cancer in this group.

GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tumors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was <10%. Chromophobe renal cell carcinoma was a unique renal tumor with frequent positivity (51%), whereas oncocytomas were positive in 17% of cases but other types only rarely. Among mesenchymal and neuroectodermal tumors, paragangliomas were usually positive, which sets these tumors apart from epithelial neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas.

Purpose: It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls., Methods: We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype., Results: Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers., Conclusion: A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.

Hereby we present a case of a pregnancy in which careful dysmorphology of the fetus in subsequent sonographic evaluation resulted in detection of a very rare anomaly. It allowed explanation of the fetal phenotype, compared then with that of the newborn and estimation of genetic risk for the next pregnancies in this family.

The relationship between the bone digital histomorphometry data of the femoral head and the age was investigated. Proximal femur samples were obtained from 31 patients, during surgery for various orthopedic conditions. The histological section, through the fovea of the femoral head was taken. Tissue sections were decalcified and stained with haematoxilin and eosin. Those sections were used for further quantization. Histological image was scanned into the computer, using digital camera. With an image analysis computer program the following static measures were determined: number, area and circumference of trabeculas, bone marrow and empty spaces. Most parameters showed a weak association, when compared with age.

The number of cases in which the estimation of age of the persons pictured in pornography materials is mandatory has been increasing for the last few years. The aim of the publication was to indicate the possibilities which are currently available for the forensic experts in this matter. The ones published heretofore mainly had focused on the difficulties which are inseparable elements of such expertise. Current publication has a demonstrative character and has been based upon the experience of two Forensic Medicine Departments. Such expertise have been constantly prepared in both of them for the last few years and none of them had to be changed till now. The currently available methods which allow for age estimation of the persons upon their photographical and movie images are far from perfection. Still authors remain skeptic about the possibility that significant progress in that matter can be achieved in predictable future. In such situation the most effective application of existing techniques becomes essential to minimize the risk of false-positive and false-negative results from appearing. Some of the difficulties pointed out by other authors are not important in practice.

In the study we presented some of the more interesting forms of artefacts which had been documented during last 7 years of the anthropological laboratory of the Forensic Med. Department of the Pomeranian Med. Univ. We also present the outgoing conclusions concerning the possible diagnostic difficulties. The descriptions of archaeological as well as autopsy-derived material were included. The anthropological analysis was made using data contained in the classic works of literature, which included cranioscopy. The longitudinal and transversal intersections of skulls were used for the analysis of their deformations.

15 cases of meningococcal infections from 2003-2004 were discussed in the study. Their therapy ended in failure and they had been typically autopsied in our Forensic Med. Department. During the autopsy material for classical microbiological investigations was collected. That type of death is characterised with pathognomonic and autopsy image. The problem is the microbiological identification of the pathogen group and type. It is connected with the characteristic of the analysed material and the biological features of Neisseria meningitidis. The molecular and genetic methods show their usefulness in this type of diagnostic of the properly selected and collected material which typically are: cerebrospinal fluid, brain tissue with the arachnoid membranes and spleen tissue.