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Although infection with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) does not appear to be as serious a threat to public health as it was in 2020–2021, the increased transmissibility of multiple Omicron descendants may constitute a continuous challenge for health care systems, and reliable detection of new variants is still imperative. This study evaluates the performance of three SARS-CoV-2 diagnostic tests: Novel Coronavirus (2019-nCoV) Real Time Multiplex RT-PCR Kit (Liferiver); Vitassay qPCR SARS-CoV-2 (Vitaassay) and TaqPath COVID‑19 CE-IVD RT-PCR Kit (Thermo Fisher Scientific). The analytical sensitivity of the assays as well as their specificity were determined with the use of synthetic nucleic acid standards and clinical samples. All assays appeared to be 100% specific for SARS-CoV-2 RNA in general and the Omicron variant in particular. The LOD determined during this validation was 10 viral RNA copies/reaction for Liferiver and TaqPath and 100 viral RNA copies for Vitassay. We cannot exclude that the LOD for the Vitassay might be lower and close to the manufacturer's declared value of ≥ 20 genome copies/reaction, as we obtained 90% positive results for 10 viral RNA copies/reaction. Mean Ct values at the concentration of 10 viral RNA copies/reaction for the Liferiver, Vitassay and TaqPath kits (35, 37 and 33, respectively) were significantly lower than the cutoff values declared by the manufacturers (≤ 41, ≤ 40 and ≤ 37, respectively). We suggest reporting outcomes based on LOD and cutoff Ct values determined during internal validation rather than those declared by the assays’ producers.

Multi-walled carbon nanotubes (MWCNTs) serve as nanoparticles due to their size, and for that reason, when in contact with the biological system, they can have toxic effects. One of the main mechanisms responsible for nanotoxicity is oxidative stress resulting from the production of intracellular reactive oxygen species (ROS). Therefore, oxidative stress biomarkers are important tools for assessing MWCNTs toxicity. The aim of this study was to evaluate the oxidative stress of multi-walled carbon nanotubes in male rats. Our animal model studies of MWCNTs (diameter ~15–30 nm, length ~15–20 μm) include measurement of oxidative stress parameters in the body fluid and tissues of animals after long-term exposure. Rattus Norvegicus/Wistar male rats were administrated a single injection to the knee joint at three concentrations: 0.03 mg/mL, 0.25 mg/mL, and 0.5 mg/mL. The rats were euthanized 12 and 18 months post-exposure by drawing blood from the heart, and their liver and kidney tissues were removed. To evaluate toxicity, the enzymatic activity of total protein (TP), reduced glutathione (GSH), glutathione S–transferase (GST), thiobarbituric acid reactive substances (TBARS), Trolox equivalent antioxidant capacity (TEAC), nitric oxide (NO), and catalase (CAT) was measured and histopathological examination was conducted. Results in rat livers showed that TEAC level was decreased in rats receiving nanotubes at higher concentrations. Results in kidneys report that the level of NO showed higher concentration after long exposure, and results in animal serums showed lower levels of GSH in rats exposed to nanotubes at higher concentrations. The 18-month exposure also resulted in a statistically significant increase in GST activity in the group of rats exposed to nanotubes at higher concentrations compared to animals receiving MWCNTs at lower concentrations and compared to the control group. Therefore, an analysis of oxidative stress parameters can be a key indicator of the toxic potential of multi-walled carbon nanotubes.

Uveal melanoma (UM) is a rare type of malignancy that originates from melanocytes located in the choroid, iris and the ciliary body of the eye. UM has a very high mortality upon metastatic spread to the liver, the prime target organ for UM metastasis. The lack of effective therapies for advanced stages of the disease aggravate the prognosis further. Moreover, biomarkers for early detection and progression of UM, especially the molecular traits governing the development of metastasis, are still not available in clinical practice. One extensively studied components of liquid biopsies are exosomes, a subtype of extracellular vesicle. Due to their unique molecular cargo, they could be used as carriers of early markers of cancer development and progression. For characterisation of the miRNA profiles present in circulating serum-derived exosomes of patients with diagnosed primary and metastatic UM, we have analysed the miRNA cargos using next-generation sequencing followed by RT-qPCR validation in a cohort of patients (control n=20; primary n=9; metastatic n=11). Nine miRNAs clearly differentiating these patient groups have been established. We show that hsa-miR-223 and hsa-miR-203a are the most promising biomarker candidates, allowing categorization of patients into local and advanced UM. Additionally, the comparison of miRNA expression levels in exosomes derived from UM patients with those derived from healthy donors, revealed that hsa-miR-144 has the potential to be used as an early marker for presence of UM. Taken together, this pilot study reveals that miRNAs extracted from circulating exosomes could be exploited as potential biomarkers in UM diagnosis and, more importantly, for indicating metastatic spread.

BACKGROUND Endometrial cancers (EC) are a heterogeneous group of malignant neoplasms differing in etiology, clinical-pathological features and prognosis. OBJECTIVES To determine the differences between the expression of selected molecular factors and find connections between them in order to isolate possible biomarkers influencing treatment options. MATERIAL AND METHODS The investigated data involved archival histological preparations obtained from uterine EC samples taken from 137 patients, treated surgically between 2007 and 2014. The immunohistochemical Dako EnVisionTM Flex+ method was applied. RESULTS The expression of ERβ, MLH1 and BRCA1 was lower in ECI than in ECII patients. The ERα expression was higher in early Federation internationale de gynecologie et d'obstetrique (FIGO) (IA) stages than in advanced (IB-IV) stages, while ERβ expression was significantly higher in advanced stages compared to stage IA and increased with grading. The BRCA1 expression also increased with grading. In both type I and type II EC patients, ERα expression correlated with MYH9 and BRCA1, while ERβ expression correlated with BAP expression. High expression of BRCA1 correlated with several proteins: BAP, MYH9 and FAK. High BAP expression also correlated with high MYH9 expression. A correlation in the expression of these proteins was also demonstrated in the group consisting only of patients with ECI. A significant correlation was found between BAP expression and MYH9 among patients diagnosed with ECI. In the ECII group, no correlation was found between the tested proteins. CONCLUSIONS The ECI and ECII patients differed in the studied molecular factors, mainly in terms of ER and BRCA1 expression. Changes in BRCA1 expression were linked to alterations in BAP expression, but were also associated with the proteins MYH9 and FAK.

Background: Due to factors such as silk sequence, purification, degradation, morphology and functionalization, each silk variant should be individually tested for potential toxicity. Aim: In vivo toxicological evaluation of the previously characterized bioengineered H2.1MS1 spider silk particles that can deliver chemotherapeutics to human epidermal growth factor receptor 2-positive breast cancer. Materials & methods: Silk nanoparticles (H2.1MS1 and control MS1) were administered intravenously to mice, and then the organismal response was assessed. Several parameters of acute and subchronic toxicity were analyzed, including animal mortality and behavior, nanosphere biodistribution, and histopathological analysis of internal organs. Also, the complete blood count, as well as the concentration of biochemical parameters and cytokines in the serum, were examined. Results & conclusion: No toxicity of the systemically administrated silk nanosphere was observed, indicating their potential application in biomedicine.

Current strategies in urinary bladder augmentation include use of gastrointestinal segments, however, the technique is associated with inevitable complications. An acellular biologic scaffold seems to be a promising option for urinary bladder augmentation. The aim of this study was to evaluate the utility of bladder acellular matrix (BAM) for reconstruction of clinically significant large urinary bladder wall defects in a long-term porcine model. Urinary bladders were harvested from 10 pig donors. Biological scaffolds were prepared by chemically removing all cellular components from urinary bladder tissue. A total of 10 female pigs underwent hemicystectomy and subsequent bladder reconstruction with BAM. The follow-up study was 6 months. Reconstructed bladders were subjected to radiological, macroscopic, histological, immunohistochemical, and molecular evaluations. Six out of ten animals survived the 6-month follow-up period. Four pigs died during observation due to mechanical failure of the scaffold, anastomotic dehiscence between the scaffold and native bladder tissue, or occluded catheter. Tissue engineered bladder function was normal without any signs of postvoid residual urine in the bladder or upper urinary tracts. Macroscopically, graft shrinkage was observed. Urothelium completely covered the luminal surface of the graft. Smooth muscle regeneration was observed mainly in the peripheral graft region and gradually decreased toward the center of the graft. Expression of urothelial, smooth muscle, blood vessel, and nerve markers were lower in the reconstructed bladder wall compared to the native bladder. BAM seems to be a promising biomaterial for reconstruction of large urinary bladder wall defects. Further research on cell-seeded BAM to enhance urinary bladder regeneration is required.

The oncological treatment can significantly affect patients’ health-related quality of life (HRQoL), which should be monitored to ensure our patients’ well-being. The often-used HRQoL measurer is the quality-adjusted life-year (QALY) indicator of the disease burden, describing both quality and quantity of life lived. The main aim of the study was to discuss the methodology and usefulness of evaluating QALYs using the HRQoL questionnaires: EuroQoL (EQ)-5 dimensions-3 levels (EQ-5D-3L) and EQ visual analogue scale (EQ-VAS) in 32 cervical cancer patients. We obtained the questionnaire and calculated QALYs based on the Gross Domestic Product (GDP) method. In our study, the total scoring of the EQ-Index, EQ-VAS evaluation was 2620 and 2409 points, respectively, which corresponds with the QALYs value of 26.2 and 24.9, respectively. We expressed the QALYs outcome into the economic equivalent of nearly 900,000 US dollars (USD) as the total health profit for both the patients and the healthcare system. Obtaining the QALY factor can help establish the medical management’s influence on the patients’ HRQoL and improve the healthcare services to ensure the best health outcomes.

Gastric cancer (GC) is the fourth most common cancer in the world in terms of incidence and second in terms of mortality. Chemotherapy is the main treatment for GC. The greatest challenge and major cause of GC treatment failure is resistance to chemotherapy. As such, research is ongoing into molecular evaluation, investigating mechanisms, and screening therapeutic targets. Several mechanisms related to both the tumor cells and the tumor microenvironment (TME) are involved in resistance to chemotherapy. TME promotes the secretion of various inflammatory cytokines. Recent studies have revealed that inflammatory cytokines affect not only tumor growth, but also chemoresistance. Cytokines in TME can be detected in blood circulation and TME cells. Inflammatory cytokines could serve as potential biomarkers in the assessment of chemoresistance and influence the management of therapeutics in GC. This review presents recent data concerning research on inflammatory cytokines involved in the mechanisms of chemoresistance and provides new clues in GC treatment.

Background/aim Immunohistochemistry (IHC) enables visualisation of the distribution of specific proteins, the differentiation of benign and malignant tumours, and the site and origin of a primary tumour. Surgical pathologists commonly examine tumours with extensive necrosis or non-viable tissue that may affect an accurate diagnosis. Materials and methods We investigated the sensitivity and specificity of IHC on necrotic samples derived from adenocarcinoma, squamous cell carcinoma (SCC) and melanoma using different markers. Results Analysis of necrosis within tumours revealed 88% sensitivity and 56% specificity for melanoma, 95% and 92% for CK5/6, 95% and 83% for CK20, 37% and 95% for p63, 69% and 97% for Melan A, 88% and 92% for SOX-10, 98% and 56% for CKAE/AE3 and 75% specificity for CK7. Conclusion Antibodies should be considered reliable markers for demonstrating the epithelial nature of a suspected tumour. Immunohistochemistry of necrotic tissues may provide clinically useful information.

The outbreak of SARS-CoV-2 coronavirus rapidly altered radiotherapy service delivery around the world. Aim The main objective of this study was to assess the impact of precautionary measures implemented in response to the COVID-19 pandemic on the performance of a radiation oncology departments and on mitigation the risk of COVID-19 contagion between and among patients and staff. Methods The study period was from March 15 until May 22, 2020. We evaluated total number of patients irradiated and those who initiated treatments, taking into account tumours localisations. We assessed the relationship of potential risk of contagion with patients’ domiciles locations in regions with high number of COVID19 case. Results and conclusions The number of patients treated with radiotherapy during the study period decreased due to precautionary measures. After five weeks, the number of radiotherapy treatments began to increase. Just over half of the radiotherapy patients (53.5%) treated at the GPCC reside in the city of Poznan or in one of the ten surrounding counties where COVID19 incidence was low and reached at the end of the study period cumulative number of cases n = 204. The precautionary measures were effective qRT-PCR tests were performed in 1545 individuals (patients and hospital staff) revealing four staff members and none patient with a positive PCR result. Immunoglobulin testing was performed in 1132 individuals (patients and hospital staff). A total of 63 individuals were positive for antibodies.

The authors present the case of a female patient with a tumor of segment VII of the liver, which was postoperatively identified as a tuberculous granuloma. The patient was admitted for elective surgery for a liver tumor, which had been diagnosed a few months before. Computed tomography and nuclear magnetic resonance were performed, based on which focal nodular hyperplasia was suspected. Thirteen years prior to admission the patient had undergone a transurethral resection of superficial bladder carcinoma, followed by adjuvant intravesical Bacillus Calmette-Guérin (BCG-therapy). Upon surgery, segment VII of the liver was resected; postoperative course was uneventful. After the identification of granuloma, the patient was referred to a phthysiatric clinic for further diagnostics and treatment. The authors have deemed this case worthy of reporting primarily due to the exceptionally long period between the completion of BCG therapy and the onset of hepatic tumor.

Aim To evaluate whether the sequential dual-time-point fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (DTP 18F-FDG PET/CT) study improves the differential diagnosis in the larynx. Background In some cases, the clinical and metabolic similarity of laryngitis and larynx cancer make differential diagnostics difficult when performing standard 18F-FDG PET/CT examinations; therefore, an additional study protocol performance seems to be of reasonable value. Materials and methods 90 patients (mean age: 61 ± 11 years, range: 41–84 years): 23 women (mean age: 63 ± 10 years, range: 51–84 years) and 67 men (mean age: 61 ± 11 years, range: 41–80 years) underwent delayed 18F-FDG PET/CT examinations at 60 and 90 min post intravenous injection (p.i.) of the radiopharmaceutical 18F-FDG. We compared the metabolic activity of 90 structures divided into following groups: normal larynx (30 patients), laryngitis (30 lesions) and larynx cancer (30 tumors) with maximal and mean standardized uptake value (SUVmax, SUVmean) and the retention index (RI-SUVmax). We used the receiver operating characteristics (ROC) curve to evaluate the SUVmax cut-off values. Results The SUVmax cut-off value at 60 and 90 min p.i. of 2.3 (sensitivity/specificity: 96.4%/100%) and 2.4 (94.2%/100%), respectively, distinguished normal and abnormal metabolic activity in the larynx. When laryngitis and tumors were compared, the SUVmax cut-off values obtained after initial and delayed imaging were 3.6 (87.5%/52.0%) and 6.1 (58.3%/84%), respectively. The RI-SUVmax of 1.3% (71.4%/88.1%) suggested abnormality, while RI-SUVmax of 6.6%, malignant etiology (75.0%/80.0%). Conclusions In this study, the sequential DTP scanning protocol improved the sensitivity and specificity of the PET/CT method in terms of differential diagnosis within the larynx.

Prostate cancer (PCa) is the second most commonly diagnosed malignant tumor and the fifth leading cause of cancer death in men in the world. The most common types of tumors are adenocarcinomas. Prostate cancer is a slow-growing cancer. The incidence increases with age. Evaluation of proinflammatory factors such as IL-17A, IL-17F, IL-17RA, and IL-17RC expression makes it possible to assess the impact of inflammatory process on progression of PCa. The aim of the study was to retrospectively assess the histological material of PCa divided into few groups using the Gleason score. Studies were carried out on archival tissue material in the form of paraffin blocks of 40 men with PCa after radical prostatectomy. The control group was composed of 10 men with benign prostatic hyperplasia (BPH). The material was obtained by the transurethral resection of the prostate (TURP). Immunohistochemistry was performed on prepared material using specific primary antibodies against IL-17A, IL-17F, IL-17RA, and IL-17RC. Expression of the antibody to be examined using light microscopy and the Remmele-Stegner score (IRS) in cancer staining was then evaluated. Expression of IL-17 RA was not shown in a group of patients with PCa and in the control group. In the group of patients with Gleason score 8 and 9 PCa, the expression of IL-17A was higher compared to that of IL-17F. In addition, in PCa with an increased grade of Gleason scale, a decrease in the expression of the study inflammatory parameters was found. The inflammatory process has an impact on PCa. A study on IL-17 may become a starting point for further research on an attempt to use, for example, immunotherapy in PCa.

Aim: The aim of our study was to evaluate the impact of surgical experience in a high volume head and neck surgery department on basal cell carcinoma margin status. Material and methods: A retrospective analysis of 546 patients surgically treated for primary basal cell carcinoma of the head and neck region was carried out. Resections were performed by 4 specialists with equal experience in head and neck surgery and 4 ENT residents at the same level of surgical training. A margin of 3–5 mm was chosen, according to guidelines. Results: The study consisted of 304 males and 242 females, mean age of 69 (range 26–100). Most of the tumors were loca-ted on the nose (165 pts; 30.2%) and auricle (119; 21.7%). The most common histological subtype was nodular (119; 21.7%). Tumor size was up to 20 mm in 394 cases (72%). Positive surgical margins were found in 112 cases (20.5%). There was no difference in terms of positive surgical margins between residents (19/119 cases; 15.9%) and specialists (93/426; 21.8%; p = 0.161). Conclusions: The results of our study have shown that adequate surgical training in a dedicated head and neck surgery de-partment is an efficient factor in obtaining free surgical margins in head and neck basal cell carcinoma.

The aim of this study is to assess the influence of semiquantitative PET-derived parameters as well as hematological parameters in overall survival in HNSCC patients using neural network analysis. Retrospective analysis was performed on 106 previously untreated HNSCC patients. Several PET-derived parameters (SUV

The study aimed to show that including the brain region into the standard 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) study protocol may result in detecting clinically silent brain tumours. We retrospectively analyzed the group of 10,378 from the total of 12,011 consecutive patients who underwent the torso and brain [18F]FDG PET/CT scanning, considering an ability of the method to evaluate undetected before brain tumours in patients diagnosed and treated in our institution. While collecting the database, we followed the inclusion criteria: at least 1-year of follow-up, a full medical history collected in our institution, histopathologic examination or other studies available to confirm the type of observed lesion, and the most importantly—no brain lesions reported in the patients’ medical data. In this study, performing the torso and brain [18F]FDG PET/CT imaging helped to detect clinically silent primary and metastatic brain tumours in 129 patients, and the benign lesions in 24 studied cases, in whom no suspicious brain findings were reported prior to the examination. In conclusion, including the brain region into the standard [18F]FDG PET/CT protocol can be considered helpful in detecting clinically silent malignant and benign brain tumours.

Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

Introduction:Physical activity during cancer treatment may reduce resulting side effects(e.g. fatigue) and improve the quality of patient’s life. It is not known, however, which typevof exercise would be the best or what the optimal duration and intensity of training should be. Neoadjuvant chemotherapy enables to evaluate the intervention effects. Young breast cancer patients are more willing to engage in intensive training than older ones. This randomised pilot study (SPORT NATHY TRIAL) evaluates the feasibility and the safety of high intensity interval physical activity during neoadjuvant chemotherapy administered to young women with breast cancer. Possible impact on treatment efficacy will be also evaluated. Methods:Young breast cancer patients (18-40 years old) were randomized to standard neoadjuvant chemotherapy (usual care - UC) or to neoadjuvant chemotherapy with 6 months of supervised high-intensity interval exercise (SHIIE). SHIIE: 2 times per week circuit on uphill treadmill walking/running, cycle ergometry, elliptical trainer from 5 × 1:15 (1st mth), 5 × 1:30 (2nd mth), 5 × 1:45 (3-4th mth) 5 × 2 min (5-6th mth) with 80%-95% HRpeak with 4 min active rest between sets; 10 min warm-up (50-60 % HRpeak) and 5 min cool-down; total time of to 40 min. Additionally once a week 45 min preferred activity (walk, run, cycling, rollerblading) 60-70 % HRpeak. Each time during training max 5 persons SHIIE groups were supervised by a physiotherapist. UC - 90 min (3 × 30min) walks per week (60% HRpeak) and patient physical therapy rules education.Each participant was monitored at all times by Polar activity monitor to measure: the number of steps, calories burnt, length of sleep, general daily heart rate with special attention placed to monitoring the heart rate during training.A biochemical analysis, bone density, cardiovascular evaluation (Digital ECG and transthoracic echocardiography, treadmill exercise test with RAMP protocol designed individually based on the score during 6 min walk test) were performed on all participants before chemotherapy and upon completion of the treatment.Specialized questionnaires and forms were used to estimate emotional status and sexual functioning.Results:We have already enrolled 22 patients. Median age was 35 in both groups. Number of trainings per week was in UC 2,5 and in SHIIE 3,1. All patients in SHIIE participated in min. 90% of supervised trainings.We were surprised to note that patients from the UC group, following the example of SHIIE group patients, increased their activity significantly. This observation was possible thanks to continuous monitoring of all patients with Polar activity monitors.Conclusions:High intensity interval physical activity may be recommended to young breast cancer patients during neoadjuvant chemotherapy and could be part of a valuable support care strategy. Hospital supervised training encourages other patients to be more physically active as well. Citation Format: Joanna Kufel-Grabowska, Slawomir Marszalek, Maciej Gorecki, Marta Malinowska, Maciej Lesiak, Ewa Straburzynska-Migaj, Wiktoria Suchorska, Janusz Dos, Piotr Nowaczyk, Alicja Nowak, Agnieszka Bartczak-Rutkowska, Magdalena Dudek, Andrzej Marszalek, Maria Litwiniuk. Supervised high intensity interval physical exercise of young women with breast cancer during neoadjuvant chemotherapy has also a positive impact on the control group (SPORT NATHY trial) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-10.

Oncological management of patients with breast cancer, with the use of pre-operative systemic therapy in the last decade presented significant increase of effectiveness. The greater the number of cases with complete or major pathomorphological response means that getting the right material for postoperative histopathological assessment is becoming more and more difficult. In addition, the demonstrated correlation between complete pathomorphological response (pCR) and long-term treatment effects (in HER2-positive and triple-negative subtypes of breast carcinoma) makes the standardisation of postoperative pathomorphological examination, both at the gross and microscopic level, a necessity. This article presents the recommended rules for the preparation of such material and the method of its reporting, corresponding to the needs of contemporary oncology.

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast carcinomas and represents an aggressive variant with a high mortality rate. PD-L1 is a protein that plays a pivotal role in suppressing the adaptive immune system. It has become a central target of the immunotherapy approach. Determining the PD-L1 status can identify TNBC patients who may benefit from targeted therapy. This study was performed to estimate the prevalence of PD-L1 expression among Polish TNBC patients. A total of 123 patients with TNBC were tested for PD-L1 expression using immunohistochemical studies. The PD-L1-positive tumors were found in 55 patients (45%), while PD-L1-negative tumors were found in 68 patients (55%). The PD-L1 positive tumors included 17 patients (31%) with the expression covering up to 1% of tumor area, 23 patients (42%) covering 2-5%, 8 patients (14%) covering 6-10% and 7 patients (13%) covering more than 10% of tumor area. The PD-L1 negative tumors included 17 patients (25%) with the expression covering less than 1% of tumor area and 51 patients (75%) with a complete lack of expression. There were no significant differences between the groups with different status of PD-L1 and the clinical tumor and lymph node stages as well as the patients’ age.

Objectives: Endometrial cancers (ECs) are the most common gynaecological cancers in well developed countries. Diabetes and metabolic syndrome are among the biggest risk factors. Nesfatin-1, the adipokine derivative of NUCB2 (nucleobindin derivative 2) is linked to the clinical course of EC. Molecular factors, including mutations in MLH1 and MHS2 genes, c-MET and ARID1A are also related to prognosis in endometrial cancer. Material and methods: Using sections of paraffin-embedded preparations and immunohistochemistry, the expression of NESF1, MLH1, MSH2,c-MET and ARID1A were examined. Results: In this study on protein expression, EC tissues manifested (although insignificantly) an elevated expression of NESF-1 in type II EC. In type I EC, NESF-1 expression was significantly higher in G1 in comparison to G2 and G3 together. A significantly lower expression of MLH1 was demonstrated in type I EC. Conclusions: The most pronounced expression involved c-MET in all EC I and EC II tissues (in over 80% of cases). A tendency was detected for a high expression of NESF-1 in patients with type II EC, who also exhibited a high expression of MSH2.

AimsThe knowledge concerning genetic background of gastrointestinal stromal tumours (GISTs) is well recognised, and the accurate detection of KIT and PDGFRα mutations is of great importance for the process of disease diagnosis and patient’s treatment. In this study, we compare the usefulness of real-time PCR-based techniques and Sanger sequencing to detect mutations of both genes in 41 formalin-fixed, paraffin-embedded GIST samples.MethodsThe analysis encompassed most frequently mutated coding regions of KIT (exons 9, 11, 13 and 17) and PDGFRα (exons 12, 14 and 18) genes. The GIST Mutation Detection Kit (EntroGen), direct Sanger sequencing and high-resolution melting (HRM) analysis were applied to conduct the study.ResultsWith the application of EntroGen kit, we found alterations in 22/38 samples, with Sanger sequencing variants were found in 36/41 samples. The concordant results for both methods were observed in 19/38 samples. With subsequently applied HRM analysis, we have confirmed that all samples, except one, harboured alterations in the regions indicated by Sanger sequencing.ConclusionsOur results show that in GIST samples, carrying a broad spectrum of deletions, Sanger sequencing is a better, more sensitive method for mutational analysis of KIT and PDGFRα genes.

Aim The aim of the study was to assess the accuracy of radiological diagnosis of laryngeal cartilage infiltration by histopathological examination of laryngeal specimen after total laryngectomy. Background Despite the development of new medical technologies and significant clinical advances allowing early diagnosis and treatment of laryngeal cancer, mortality is still on the rise. Neoplastic infiltration of the laryngeal cartilages is the most common source of error in the assessment of cancer staging. Furthermore, cartilage invasion is listed as a contraindication to partial surgical techniques as well as radiotherapy. Materials and methods The study was carried out on 21 larynges following total laryngectomy. Before taking the decision to perform surgery, high-resolution CT scans were performed in all cases. An extended histopathological examination was conducted using a unique vertical cross-section of the whole larynx. Results Pathology reported 2 cases of arytenoid cartilage invasion, 5 cases of cricoid cartilage invasion, 12 cases of thyroid cartilage penetration, 1 case of internal cortex invasion and 9 cases of extra-laryngeal spread. CT imaging identified 8 of 13 cases (61.5%) of pathologically proven invasion of thyroid cartilage and only 2 cases (2/9, 22%) of extra-laryngeal spread. According to CT results, arytenoid cartilage invasion was correctly identified in 2 cases, cricoid cartilage invasion in 4 (4/5, 80%). The positive predictive values for thyroid, cricoid and arytenoid cartilage invasion and penetration were 80%, 66.7% and 50%, respectively. In case of pre-laryngeal spread the positive predictive value was 100%. Conclusion Despite increasingly advanced methods involved in the diagnosis of laryngeal cancer, many discrepancies may be observed between the radiological and histopathological assessments. CT imaging has limitations especially in thyroid cartilage penetration and extra-laryngeal spread assessment in advanced laryngeal cancer cases. An extended histopathological examination, involving vertical cross-sections of the whole larynx is a very precise study that allows a precise determination of local cancer staging (T).

BACKGROUND The role of molecular markers in salivary gland carcinoma (SGC) is not well understood. We evaluated molecular marker expression and their prognostic value. METHODS Immunohistochemical analysis of 124 tumor specimens was performed to determine expression of androgen (AR), estrogen (ER), and progesterone (PR) receptors and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 receptor (PD-L1), and PD-L1 in tumor-infiltrating mononuclear cell (TIMC). Survival outcomes (disease-free survival [DFS] and overall survival [OS]), pT and N classification, margin status, and treatment failure were assessed. RESULTS Most patients (78; 62.9%) had early-stage SGC. AR positivity and EGFR positivity were detected in 21.0% and 78.6%, respectively, of tumors. AR positivity and PD-L1 negativity were associated with locally advanced disease. PD-L1-negativity was associated with higher recurrence (38.5% vs 0%; P

Nowotwory tarczycy są najczęściej występującymi wśród nowotworów układu wewnątrzwydzielniczego. W ciągu ostatnich dekad liczba nowych zachorowań znacząco wzrosła i wciąż wykazuje tendencję wzrostową. U podstaw choroby nowotworowej leżą zmiany zachodzące w komórkach na poziomie molekularnym, głównie mutacje somatyczne w określonych onkogenach lub genach supresorowych. Analiza profilu molekularnego w zakresie mutacji somatycznych występujących w genach związanych z nowotworami tarczycy pozwala na poszerzenie wiedzy na temat molekularnych podstaw nowotworzenia i poznanie roli ich genetycznego podłoża w rozwoju choroby, jej progresji i rokowaniu powodzenia terapii. Mutacje w genach z rodziny RAS (NRAS, KRAS, HRAS) związane są najczęściej z typem pęcherzykowym nowotworu tarczycy, ale wykrywane są także w przypadku typu anaplastycznego. Mutacje w genie BRAF związane są natomiast z typem brodawkowym, ale również mogą występować w typie anaplastycznym. Mutacje w genie TP53 lub regionie promotorowym genu TERT związane są z większą agresywnością nowotworu, przerzutami i gorszym rokowaniem dla chorego.

Background: The prognostic value of commonly recurrent mutations remains unclear in mucosal melanomas. Methods: Clinicopathologic parameters of 214 cases of mucosal melanomas diagnosed in 1989–2020 in several clinical institutions were analyzed. NRAS, KIT, BRAF, IGF2R and SF3B1 mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. Results: Of the triple (BRAF, NRAS, NF1)-negative cases, APC, KIT and KRAS are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. NRAS, KIT, BRAF, IGF2R and SF3B1 mutations are detected in 19% (37/198), 22% (44/197), 12% (25/201), 16% (22/138) and 15% (20/133) of cases, respectively. In univariate analyses, advanced stage (p = 0.016), 65 years or older (p = 0.048) and presence of ulceration (p = 0.027) are significantly correlated with worse overall survival (OS), respectively. NRAS mutation significantly correlates with worse OS (p = 0.028) and worse melanoma-specific survival (MSS) (p = 0.03) for all cases of mucosal melanomas. In multivariate analyses, NRAS mutation remains as an independent predictor of worse OS (p = 0.036) and worse MSS (p = 0.024). Conclusion: NRAS mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated IGF2R in mucosal melanomas remains unclear.

MAF is a transcription factor that may act either as a tumor suppressor or as an oncogene, depending on cell type. We have shown previously that the overexpressed miR-1290 influences MAF protein levels in LSCC (laryngeal squamous cell carcinoma) cell lines. In this study, we shed further light on the interaction between miR-1290 and MAF, as well as on cellular MAF protein localization in LSCC. We confirmed the direct interaction between miR-1290 and MAF 3′UTR by a dual-luciferase reporter assay. In addition, we used immunohistochemistry staining to analyze MAF protein distribution and observed loss of MAF nuclear expression in 58% LSCC samples, of which 10% showed complete absence of MAF, compared to nuclear and cytoplasmatic expression in 100% normal mucosa. Using TCGA data, bisulfite pyrosequencing and CNV analysis, we excluded the possibility that loss-of-function mutations, promoter region DNA methylation or CNV are responsible for MAF loss in LSCC. Finally, we identified genes involved in the regulation of apoptosis harboring the MAF binding motif in their promoter region by applied FIMO and DAVID GO analysis. Our results highlight the role of miR-1290 in suppressing MAF expression in LSCC. Furthermore, MAF loss or mislocalization in FFPE LSCC tumor samples might suggest that MAF acts as a LSCC tumor suppressor by regulating apoptosis.

Simple Summary Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. Despite good knowledge of the histological and genetic background of metastases formation, there is still a lack of specific biomarkers which would allow early detection of UM progression. Due to their unique molecular cargo consisting of proteins and nucleic acids, exosomes have been widely studied as carriers of biomarkers for cancer development and progression. In this study, we analyzed the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors using multiplex immunoassay technology. We showed a significant correlation between the disease stage and the concentration of inflammation-related proteins from exosomal cargo. Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease. Abstract Background: Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. However, despite relatively good knowledge about the histological and genetic risk factors for metastasis development, there is no specific biomarker that would allow early detection of UM progression. Recently, exosomes and their molecular cargo have been widely studied in the search for potential biomarkers in several cancers. The purpose of this study was to analyze the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors. Methods: The exosomes were isolated from the serum of primary and metastatic UM patients and healthy donors. Using multiplex immunoassay technology, we analyzed the concentration of 37 inflammation-related proteins in obtained exosomes. Results: The analysis of protein cargo showed several molecules related to inflammation, such as interferon-gamma, interleukin 2, 22 and 12(p40), Pentraxin-3, TNFSF13B and TNFSF8 which were significantly enriched in metastatic UM exosomes. We showed a significant correlation between the disease stage and the concentration of these inflammation-related proteins from exosomal cargo. Conclusions: Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease.

Simple Summary Merkel cell carcinomas (MCCs) of unknown primary are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. We compared the immunohistochemical profiles of four groups of Merkel cell carcinomas (virus-positive and virus-negative unknown primary tumors and virus-positive and virus-negative cutaneous tumors) and performed molecular studies on the unknown primary tumors. Virus-positive and virus-negative Merkel cell carcinomas of unknown primary (MCC-UPs) exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. Similar to primary cutaneous Merkel cell carcinomas, virus-negative unknown primary tumors exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in virus-positive tumors. Although additional studies are warranted for the virus-positive cases, our findings are supportive of a cutaneous metastatic origin for virus-negative Merkel cell carcinomas of unknown primary. Abstract Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. Methods: We compared the immunohistochemical profiles of four groups of MCCs (Merkel cell polyomavirus (MCPyV)-positive UP, MCPyV-negative UP, MCPyV-positive known primary (KP), and MCPyV-negative KP) using B-cell and pre-B-cell markers, cell cycle regulating proteins, follicular stem cell markers, and immune markers, and performed next generation and Sanger sequencing. Results: Virus-positive and virus-negative MCC-UPs exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. MCC-UP tumors (both virus-positive and -negative) were immunogenic with similar or even higher tumoral PD-L1 expression and intratumoral CD8 and FoxP3 infiltrates in comparison to MCPyV-positive cutaneous tumors. In addition, similar to primary cutaneous MCCs, MCPyV-negative MCC-UPs exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in MCPyV-positive MCC-UPs. Conclusions: Our results showed distinct UV-signatures in MCPyV-negative tumors and high immunogenicity in MCPyV-positive tumors. Although additional studies are warranted for the MCPyV-positive cases, our findings are supportive of a cutaneous metastatic origin for MCPyV-negative MCC-UP tumors.

This study developed a new procedure of urinary bladder transplantation on a rat model (n = 40). Heterotopic urinary bladder transplantation (n = 10) in the right groin vessels was performed. Direct urinary bladder examination, microangiography, histological analysis, and India ink injection were performed to evaluate the proposed method's functionality. Observation time was four weeks. One week after the procedure, the graft survival rate was 80%, two urinary bladders were lost due to anastomosis failure. The rest of the grafts survived two weeks without any complications. Lack of transitional epithelium or smooth muscle layer loss and lack of inflammatory process development were observed. This study was performed in order to obtain the necessary knowledge about urinary bladder transplantation. The proposed technique offers a new approach to the existing orthotropic models.

Introduction Cardiotoxic effect of chemotheraphy represents known and challenging problem, thus search for potentially cardioprotective factors plays a key role in the contemporary cardio-oncology. Physical activity may allievate side effects of chemotheraphy and improve quality of live. Myocardial Work is a novel echocardiographic technique and promising tool for cancer patients assesement. Purpose The aim of this randomised pilot study was to assess left ventricle function using speckle tracking myocardial strain (2D STE) with Myocardial Work (MW) module in young women undergoing neoadjuvant chemotheraphy due to breast cancer and the impact of supervised high-intensity interval physical activity on these echocardiographic parameters. Material and methods We evaluated 24 women aged 27–41 (mean 34±4 yrs) with invasive breast cancer undergoing standard neoadjuvant chemotheraphy and randomized them into two groups: control - (CG, 15 pts) and experimental - with 6 months of supervised high-intensity interval exercise (SHIIEG, 9 pts). Every patient underwent echocardiographic examination 2D STE and MW before chemotheraphy and at 6 months follow-up. The following parameters were evaluated: Global Longitudinal Strain (GLS), Global Work Index (GWI), Global Constructive Work (GCW), Global Work Efficiency (GWE), Global Waste Work (GWW). Results Following parameters significantly decreased after chemotherapy: EF (65.4±5.7 vs 60.5±7.0%; p=0.003), GLS (20.4±2.5 vs 18.4±2.0%; p=0.001), GWI (1835.4±206.9 vs 1594.1±228.3 mmHg%; p=0.0004), GCW (2240.5±270.8 vs 1884.9±241.3 mmHg%; p=0.0001), GWE (95.9±1.5 vs 94.9±1.7%; p=0.02). No signifficant changes in GWW (78.6±36.4 vs 80.5±32.2 mmHg%; p=0.7) were found. The comparison of control (CG) and experimental group (SHIIEG) at 6 months follow-up revealed no signifficant differences in the following parameters: GLS (p=0.9), GWI (p=0.3), GCW (p=0.2), GWE (p=0.3) and GWW (p=0.5). However analysis of relative percentage change from baseline in GLS and GWW (Δ%GLS, Δ%GWW) almost reached statistical significance [for CG and SHIIEG respectively: Δ%GLS (−15.6 vs −4.4; p=0.07), Δ%GWW (+39.4 vs −7.3; p=0.06)]. Conclusions Neoadjuvant chemotherapy administered in young women with invasive breast cancer impaires the function of left ventricle after 6 month of theraphy, resulting in decrease of GLS, GWI, GCW and GWE. The supervised high-intensity interval physical activity impacts the relative change of GLS (Δ%GLS) and GWW (Δ%GWW), therefore may have cardioprotective effect on left ventricle function. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Greater Poland Cancer Centre, Poznan, Poland

One of the most critical elements in the palatine tonsils (PT) patients&rsquo, management is to distinguish chronic tonsillitis and malignant tumor. The single-time-point (STP) 2-deoxy-2-[18 F]fluoro-D-glucose positron emission tomography/computed tomography (18 F-FDG PET/CT) examination offers the most significant sensitivity and specificity in the head and neck (H&amp, N) region evaluation among commonly used methods of imaging. However, introducing dual-time-point (DTP) scanning might improve the specificity and sensitivity of the technique, limited by the 18 F-FDG non-tumor-specific patterns, especially when comparing different metabolic parameters. The study aims to compare several surrogates of the maximal standardized uptake value (SUVmax), obtained in 36 subjects, divided into confirmed by pathologic study PT cancer and tonsillitis in patients who underwent DTP 18 F-FDG PET/CT scanning. In this study, we observed the increased sensitivity and the specificity of the DTP 18 F-FDG PET/CT when compared with the standard PET/CT protocol. It could be concluded that DTP 18 F-FDG PET/CT improves the PT cancer and chronic tonsillitis differential diagnosis.

BACKGROUND The aim of this article was to evaluate the usefulness of sequential dual-time-point 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (DTP [18F]FDG PET/CT) in distinguishing physiologic, inflammatory and malignant palatine tonsils as difficult to differentiate in the oncological practice. METHODS A total of 90 patients before the treatment underwent sequential DTP [18F]FDG PET/CT examinations. We analyzed 104 structures in 90 patients: 31 physiologic tonsils, 28 histopathologically confirmed inflammatory tonsils of non-specified origin, 31 histopathologically confirmed palatine tonsils cancer and 14 non-malignant contralateral tonsils in patients with histopathologically confirmed unilateral palatine tonsil malignancy. Patients underwent sequential [18F]FDG PET/CT examinations at 60 and 90 minutes post-injection of the [18F]FDG. We analyzed the SUVmax and SUVmean values at 60 and 90 minutes post-injection changes over time and the Retention Index (RI-SUVmax). To find the predictive SUV value and the RI cut-off between physiology, inflammatory and malignancy, we used the ROC analysis. RESULTS The average SUVmax values at 60 and 90minutes post-injection within physiologic palatine tonsils were 1.36±0.26 and 1.31±0.26, respectively, P>0.05. The average SUVmax values at 60 and 90 minutes post-injection within inflammatory and malignant tonsils were 3.74±1.45, 3.80±1.47 (P>0.05) and 5.19±2.19, 5.81±2.50 (P

Background Alveolar capillary dysplasia (ACD) is a rare cause of severe pulmonary hypertension and respiratory failure in neonates. The onset of ACD is usually preceded by a short asymptomatic period. The condition is refractory to all available therapies as it irreversibly affects development of the capillary bed in the lungs. The diagnosis of ACD is based on histopathological evaluation of lung biopsy or autopsy tissue or genetic testing of FOXF1 on chromosome 16q24.1. Here, we describe the first two Polish patients with ACD confirmed by histopathological and genetic examination. Case presentation The patients were term neonates with high Apgar scores in the first minutes of life. They both were diagnosed prenatally with heart defects. Additionally, the first patient presented with omphalocele. The neonate slightly deteriorated around 12th hour of life, but underwent surgical repair of omphalocele followed by mechanical ventilation. Due to further deterioration, therapy included inhaled nitric oxide (iNO), inotropes and surfactant administration. The second patient was treated with prostaglandin E1 since birth due to suspicion of aortic coarctation (CoA). After ruling out CoA in the 3rd day of life, infusion of prostaglandin E1 was discountinued and immediately patient’s condition worsened. Subsequent treatment included re-administration of prostaglandin E1, iNO and mechanical ventilation. Both patients presented with transient improvement after application of iNO, but died despite maximized therapy. They were histopathologically diagnosed post-mortem with ACD. Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. Conclusions Both patients presented with a distinct course of ACD, extra-pulmonary manifestations and response to medications. Surgery and ceasing of prostaglandin E1 infusion should be considered as potential causes of this variability. We further highlight the necessity of thorough genetic testing and histopathological examination and propose immunostaining for CD31 and CD34 to facilitate the diagnostic process for better management of infants with ACD.

Sinonasal melanomas encompass melanoma arising in the nasal cavity and paranasal sinuses. Despite recent advances in tumor genomics, correlation between mutational status and protein expression with prognosis and tumor pigmentation has not been carried out in sinonasal melanomas. Ninety-five sinonasal melanomas from 95 patients were included. As per univariate analyses, age was the only variable that significantly correlated with progression-free survival. SF3B1, NRAS, KIT, and BRAF mutations were documented in 7% (5/72), 22% (16/72), 22% (16/72), and 8% (6/72) of cases, respectively. Comutation was detected in 6 cases: NRAS and KIT in 2 cases; NRAS and BRAF in 2 cases; SF3B1, KIT, and BRAF in one case; and SF3B1, NRAS, and KIT in one case. Correlations approaching statistical significance were observed between BRAF mutation status and poorer overall survival and progression-free survival (log-rank P-values=0.054 and 0.061). Increased CD117 expression (33%, 29/88) and decreased nuclear cMYC expression (40%, 39/84) significantly correlated with cytoplasmic pigmentation. Several SF3B1, NRAS, and KIT mutations not previously documented in sinonasal melanomas were detected in our series, suggesting a potential role for targeted therapies. A similar frequency of SF3B1, NRAS, and KIT mutations was noted in Asian cases, whereas NRAS, KIT, and BRAF mutations were predominant in the United States and European cases; however, the number of included cases was small. The significant association between CD117 and cMYC expression with increased cytoplasmic pigmentation in our series suggests that the pigmented morphologic appearance of sinonasal melanomas could be attributed to the underlying oncogenic mutations and metabolic interaction.

Green tea contains many polyphenolic constitutes, which might prevent non-alcoholic fatty liver disease (NAFLD). We aimed to investigate whether green tea extract (GTE) given at doses reflecting habitual consumption of green tea beverages prevents development of NAFLD in rats fed a high-fat diet (HFD). Twenty-four male Wistar rats were randomly divided into four equal groups (two study and two control groups). The study groups received a HFD (approximately 50% energy from fat), enriched with 1.1% and 2.0% GTE, respectively, for a total of 56 days. The control groups were fed a HFD alone and normal standardised diet (low-fat diet), respectively, for the same period of time. The percentage of hepatocytes affected by steatosis in the HFD group (median [1st-3rd quartile]: 25% [12-34%]) was higher (p < 0.033 and p < 0.050, respectively) than in the HFD-2.0%GTE group (9% [3-18%]) and normal diet group (10% [5-18%]). No significant differences were observed for the group consuming HFD-1.1%GTE, in which intermediate results were observed (15% [4-30%]). This finding points towards the hepatoprotective potential of GTE in preventing dietary-induced liver steatosis. In view of the increasing incidence of overweight and obesity a simple and cheap dietary modification, such as GTE supplementation, could prove to be useful clinically.

Introduction To date, several nuclear DNA variants have been shown to be associated with increased risk of developing colorectal cancer. Despite the fact that mitochondria play an important role in carcinogenesis, little is known about inherited mitochondrial DNA mutations that could be involved in this disease. Thus, potential associations between inherited mutations in the entire mitochondrial genomes and colorectal cancer were analysed in this study. Material and methods Two hundred mitogenome sequences determined for colorectal cancer patients and healthy individuals from Poland were used to investigate the association between mtDNA alleles or haplogroups and colorectal cancer. Additional mtDNA control region haplotypes determined for 1353 individuals from the general Polish population were used for comparison of haplogroup and certain allele frequencies between case and control groups. Results The non-R clades together with their diagnostic T alleles at positions 12705 and 16223 were observed with higher frequencies in healthy individuals than in colorectal cancer patients. Nevertheless, the differences of the R macrohaplogroup (as well as 12705 or 16223 alleles) frequencies between cases and controls were statistically insignificant after Bonferroni correction. Most of the non-R clades were of Asian and African origin, but none of them were prevalent in the control group. Moreover, neither mtDNA alleles nor haplogroups were associated with clinicopathological parameters of colorectal cancer patients. Conclusions Contrary to some previous reports, the findings of this study do not support the hypothesis that mitochondrial DNA variants contribute to inherited predisposition to colorectal cancer.

Introduction: Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes. Little is known about the prognostic significance as well as possible associations between PARP1 and immunologic response in mucosal melanoma. Methods: PARP1, PD-L1 and IDO1 immunostains were performed on 192 mucosal melanomas including 86 vulvar, 89 sinonasal, and 17 anorectal melanomas. Results: By Kaplan&ndash, Meier analyses, high PARP1 expression correlated with worse overall and melanoma-specific survival (log-rank p values = 0.026 and 0.047, respectively). Tumors with combined PARP1 and IDO1 high expression correlated with worse overall and melanoma-specific survival (p = 0.015, 0.0034 respectively). By multivariate analyses, high PARP1 expression remained a predictor of worse survival independent of stage. By Fisher&rsquo, s exact test, high PARP1 expression correlated with highly mitogenic tumors (p = 0.02). High tumoral PD-L1 and IDO1 expression were associated with ulcerated primary tumors (p = 0.019, 0.0019, respectively). By linear regression analyses, correlations between PARP1 expression versus IDO1 expression (p = 0.0001) and mitotic index (p = 0.0052) were observed. Conclusion: Increased expression of PARP1 is an independent negative prognostic marker in mucosal melanomas. The association between PARP1 and IDO1 and their combined adverse prognostic role raise the potential of combined therapy in mucosal melanoma.

Background: Conventional treatments for follicular thyroid cancer (FTC) can be ineffective, leading to poor prognosis. The aim of this study was to identify mutations associated with FTC that would serve as novel molecular markers of the disease and its outcome and could potentially identify new therapeutic targets. Methods: FLT3 mutations were first detected in a 29-year-old White female diagnosed with metastasized, treatment-refractory FTC. Analyses of FLT3 mutational status through next-generation sequencing of formalin-fixed, paraffin-embedded FTC specimens were subsequently performed in 35 randomly selected patients diagnosed with FTC. Results: FLT3 mutations were found in 69% of patients. FLT3 mutation-positive patients were significantly older than those that were FLT3 mutation-negative [median age at diagnosis 54 (36–82) versus 45 (27–58) ( p = 0.023)]. Patients over 60 years were 23 times more likely to be FLT3 mutation-positive ( p = 0.006). However, the number of FLT3 mutations did not correlate with age ( r -Pearson: –0.244, p -value: 0.25). A total of 26 mutations were identified in the FLT3 gene with 2–16 FLT3 mutations in each FLT3 mutation-positive patient (mean: 5.6 mutations/patient). Tyrosine kinase domain (TKD) mutations in the FLT3 gene were detected in 58% of FLT3 mutation-positive patients. All FLT3 mutation-positive patients with a disease stage of pT2N1 or worse harbored at least one mutation in the TKD of FLT3 . Conclusions: There is a wide spectrum and high frequency of FLT3 mutations in FTC. The precise role of FLT3 mutations in the genesis of FTC, as well as its potential role as a therapeutic target, requires further investigation.

New recommendations for HER2 status (receptor or gene) testing in breast cancer were published following long-term analysis of clinical effectiveness of molecularly targeted treatment based on predictive factor of HER2 status. The new protocols were developed to eliminate equivocal cases, and the new procedure leads to final statement as HER2 positive or HER2 negative. Current testing algorythms are presented.

Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-κB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic-dichorionic and monoamniotic-dichorionic twins. Monoamniotic-monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-κB, NOD2 and TLR-2 between twins. In case of twin-to-twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment.

The aim of this study is to assess the influence of semiquantitative PET-derived parameters as well as hematological parameters in overall survival in HNSCC patients using neural network analysis. Retrospective analysis was performed on 106 previously untreated HNSCC patients. Several PET-derived parameters (SUVmax, SUVmean, TotalSUV, MTV, TLG, TLRmax, TLRmean, TLRTLG, and HI) for primary tumor and lymph node with highest activity were assessed. Additionally, hematological parameters (LEU, LEU%, NEU, NEU%, MON, MON%, PLT, PLT%, NRL, and LMR) were also assessed. Patients were divided according to the diagnosis into the good and bad group. The data were evaluated using an artificial neural network (Neural Analyzer version 2.9.5) and conventional statistic. Statistically significant differences in PET-derived parameters in 5-year survival rate between group of patients with worse prognosis and good prognosis were shown in primary tumor SUVmax (10.0 vs. 7.7; p = 0.040), SUVmean (5.4 vs. 4.4; p = 0.047), MTV (23.2 vs. 14.5; p = 0.010), and TLG (155.0 vs. 87.5; p = 0.05), and mean liver TLG (27.8 vs. 30.4; p = 0.031), TLRmax (3.8 vs. 2.6; p = 0.019), TLRmean (2.8 vs. 1.9; p = 0.018), and in TLRTLG (5.6 vs. 2.3; p = 0.042). From hematological parameters, only LMR showed significant differences (2.5 vs. 3.2; p = 0.009). Final neural network showed that for ages above 60, primary tumors SUVmax, TotalSUV, MTV, TLG, TLRmax, and TLRmean over (9.7, 2255, 20.6, 145, 3.6, 2.6, respectively) are associated with worse survival. Our study shows that the neural network could serve as a supplement to PET-derived parameters and is helpful in finding prognostic parameters for overall survival in HNSCC.

The aim of this study is to report the use of ruthenium brachytherapy as an adjunctive treatment in the management of an intraocular extension of the conjunctival squamous cell carcinoma (SCC). In 2013, a 73-year-old man presented with a tumor blocking the angle and infiltrating corneal endothelium. The patient was treated with iridectomy, and after one month, ruthenium brachytherapy was applied. 4.5 years post-irradiation, the treated eye is painless, and no recurrence was noted. We advocate the use of ruthenium brachytherapy as an eye salvage treatment with an intraocular extension of conjunctival SCC.

Background/Aims: Cardiovascular complications are responsible for increased mortality and morbidity in chronic kidney disease (CKD) patients. Functional and structural changes of peritoneal membrane are reported in CKD patients both on conservative treatment and on renal replacement therapy (RRT). The aim of the study was to assess the structure of peritoneal membrane small arteries (precapillary arterioles) in diabetic and non-diabetic CKD stage 5 patients before initiation of peritoneal dialysis (PD) and evaluate its relationship with heart and large arteries abnormalities and with selected biochemical parameters. Methods: Evaluation of 42 CKD stage 5 patients before starting PD. Diabetic (n=26) and non-diabetic (n=16) patients were compared. Peritoneal membrane samples were taken during Tenckhoff catheter insertion. Histopathological evaluation of peritoneal precapillary arterioles (arteriolar evaluation) with measurement of wall thickness (WT) and calculation of lumen/vessel (L/V) ratio was performed in each patients. Echocardiography, intima media thickness (IMT), pulse wave velocity (PWV), ambulatory blood pressure monitoring (ABPM) and biochemical parameters assessment: serum albumin (SA), total cholesterol (TCH), hemoglobin (Hgb), parathormone (PTH), serum calcium (Ca), serum phosphorus (P), transferrin saturation (TSAT%), C-reactive protein (CRP) were performed in each participant. Results: There were no statistically significant differences in peritoneal membrane arteriolar indices – wall thickness (WT) and L/V ratio between investigated groups. There was statistically significant higher PWV value in diabetic patients. There were no statistically significant differences in echocardiographic indices, IMT, laboratory data in analyzed groups. There were some linear correlations between: PWV vs IMT (R=0,84; p=0,0006); PWV vs PP (R=0,58; p=0,03) in non-diabetic and linear correlation between: PWV vs age (R=0,75; p=0,02); WT vs DP (R=-0,93; p=0,001); WT vs DBP ( R=0,64; p=0,04) in diabetic group. Conclusion: Peritoneal membrane arteriolar damage seems to be an integrated part of cardiovascular system damage in CKD stage 5 patients.

Introduction While it is clear that individuals with outdoor occupations are at a significantly greater risk of developing cutaneous squamous cell carcinoma (cSCC), no previous studies have investigated the potential association between the tumour grade and occupation in this patient population. Aim To assess occupation as a risk factor for the development of high-grade cSCC. Secondarily, to determine the association between the tumour grade and other clinical characteristics. Material and methods Retrospective analysis of 256 patients treated for head and neck cSCC at our institution in 2007–2016. The following patient characteristics and variables were assessed: age; sex; tumour location and grade; profession; and education level. A univariate analysis was performed to assess the association between each study variable and grade 3 tumour differentiation. Results The following variables were significantly associated (p < 0.05) with grade 3 (G3) cSCC tumours: outdoor work vs. indoor work; primary school vs. high school education; and age. Additionally, patients with low-grade (G1) tumours were significantly younger (mean age: 72) than patients with high-grade (G3) tumours (mean age: 79) (p = 0.046). Conclusions To our knowledge, this is the first study to assess the variables associated with the tumour grade among outdoor workers. These findings suggest that outdoor workers who develop cSCC are at a greater risk of developing more aggressive cancers. These findings provide additional support for classifying cSCC as an occupational disease. Early education about the dangers of sun exposure during the first years of school is essential to minimize the risks of developing high-grade skin cancer.

Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p p FAM107A expression (5 to 6 fold increase) in the UT-SCC-29 cell line, characterized by high DNA methylation. Therefore, we report the recurrent inactivation of FAM107A in LSCC, what may suggest that the gene is a promising tumor suppressor candidate involved in LSCC development.