Immunohistochemical expression of PARP-1 in triple-negative endometrial cancer - a comparison of different score systems.

Endometrial cancer is the most common malignant neoplasm of the female reproductive system. The number of diagnosed cases is increasing every year. In recent years, the triple-negative phenomenon (TNP) has been identified as one of the determinants of shorter survival in endometrial cancer patients. The aim of the study was to compare the PARP-1 protein expression in triple-negative (TNEC) and non-triple-negative (NTNEC) endometrial cancer patients and determine the relationship between the PARP-1 protein expression in endometrial cancer cells and patient's overall survival depending on the adopted scale (H-SCORE < 75, H-SCORE < 50, Allred scale). The study involved 265 patients with histopathologically confirmed endometrial cancer. The patients were divided into 2 groups: patients with TNEC and patients with NTNEC. The study was conducted using a tissue microarray technique. Expression of PARP-1 protein was determined by immunohistochemistry. Protein expression evaluation was performed using virtual microscopy and the Image Scope computer image analysis system. The following conclusions were reached: total and individual levels of nuclear or cytoplasmic PARP-1 expression varied with the presence or absence of TNP, and PARP-1 nuclear expression at the 2+ level had a significant effect on the increased risk of death (according to H-SCORE < 75).

Can the Determination of HE4 and CA125 Markers Affect the Treatment of Patients with Endometrial Cancer?

The aim of our research was to determine the use of CA125 and HE4 as prognostic factors in patients with different clinical staging of endometrial cancer. Sixty-two patients with advanced endometrial cancer and 287 patients with early stage endometrial cancer participated in the study. Based on the results obtained in the study, the cut-off value for HE4 was established at 186 pmol/l and correlated with the possibility of cytoreductive surgery in patients with recurrent endometrial cancer. Univariate logistic regression revealed that serum concentrations for the median CA125 correlated with DFS (HR = 1.76, p = 0.033) and OS (HR = 1.42, p = 0.025), while the median of HE4 marker correlated with DFS (HR = 1.96, p = 0.015) and OS (HR = 1.83, p = 0.004). In the multivariate analysis, a decrease in CA125 level below normal range correlated positively with DFS and OS (HR = 1.45, p = 0.026; HR = 1.38, p = 0.037). HE4 levels correlated with DFS as follows: values below the normal range (HR = 2.31, p = 0.01), and with OS (HR = 1.89, p = 0.004). Based on the results obtained in the study, we found that HE4 is a sensitive tool for predicting the risk of recurrence and overall survival in patients with endometrial cancer.

Triple negative phenomenon in endometrial cancer: recognition criteria and impact on survival.

OBJECTIVES: Endometrial cancer is the most common malignant cancer of female reproductive organs. The number of diagnosed cases of endometrial cancer is increasing from year to year. Endometrial cancer is a neoplasm with a good survival rate. However, there are also cases with a fast, aggressive course. In recent years, the triple negative phenomenon (TNP) has been identified as one of the factors determining shorter survival in patients with endometrial cancer. MATERIAL AND METHODS: The study covered 265 patients with histopathologically confirmed endometrial cancer. Patients were divided into two groups: 1) patients with endometrial cancer with TNP; 2) patients with endometrial cancer without TNP. Tissue microarrays (TMA) were examined with immunohistochemistry to evaluate the expression of estrogen, progesterone and HER2 receptors. In several cases FISH method was used to assess HER2. The expression was evaluated by computer image analysis using the Nuclear Image Analysis virtual microscopy system. The evaluation of HER2 expression was performed manually. The criterion for TNC diagnosis was H-Score < 50 or < 75 and Allred score < 4. RESULTS: Depending on the scoring system used, TNP was found in from 10.19% to 15.09% of cases. Regardless of the criteria employed in endometrial cancer, the presence of TNP was neither a factor increasing the risk of death nor it affected the patients' survival. CONCLUSIONS: The proportion of TNP diagnosed in endometrial cancer depends on the examined population and the diagnostic criteria. The incidence of TNP did not affect the survival of patients.

Adherence to Gluten-Free Diet in Children with Celiac Disease.

Celiac disease (CD) can only be treated by rigorous life-long gluten-free diet (GFD). The study included 102 mothers and their CD children treated with GFD for at least two years. Frequency and cause of diet failure in children treated at present (54 children) and 10 years ago (48 children) were compared. Dietary adherence was evaluated serologically (tTG), while diet management difficulties were examined by means of a questionnaire. The study shows that one-third of patients fail to follow GFD, more often 10 years ago than now (40% vs. 26%; p < 0.05), mainly children aged 13⁻18 (54% vs. 40% now; p < 0.05). Younger children (up to 12) are less likely to abandon the diet (27% vs. 8%; p < 0.05). In this age group non-intentional diet failure prevails, while teenagers interrupt their diet intentionally (45% vs. 33%; p = ns (small population of children in this groups)). Currently, the most common causes of teenage diet failure are the absence of symptoms after consuming a small amount of gluten and, even more often, troublesome diet administration. Previously, the absence of peer acceptance prevailed. With this study we found that: 1. In West Pomerania, every fourth CD child does not follow GFD. 2. For years, teenagers have failed to follow GFD due to the absence of symptoms after consuming small amounts of gluten. 3. The incidence of non-intentional failure to follow GFD has significantly decreased over years, which indicates better dietary care.

Clinical Relevance of NGAL/MMP-9 Pathway in Patients with Endometrial Cancer.

The objectives of the study were to assess the relationship between the serum levels of MMP-9 and NGAL and the clinical staging and histopathological grade of the tumor. Lipocalin-2/NGAL and MMP-9 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation, Austin, TX, USA). The AUC values for NGAL and MMP-9 were 0.9 and 0.78, respectively. The diagnostic potential of NGAL and MMP-9 in differentiating high-stage (FIGO III and IV) and low-stage (FIGO I and II) cancer and predicting the cell differentiation grade (G1 versus G3) on the basis of the analyses of AUC values was determined to be 0.91 and 0.79 for NGAL and 0.82 and 0.84 for MMP-9, respectively. Multifactorial logistic regression analysis in the final method revealed that NGAL and MMP-9 variables were independent of the endometrial cancer risk. OR values for NGAL and MMP-9 were 1.23 (95% CI 1.421-3.27; p = 0.034) and 1.09 (95% CI: 1.38-4.12; p = 0.026), respectively. The NGAL/MMP-9 complex may be useful in the assessment of tumor stage before surgical treatment.

Triple negative endometrial cancer.

Endometrial cancer (EC) is the most common malignancy of the female genital tract in the developed countries. In Poland, EC incidence increased from 3.496 to 5.251 between 2000 and 2011, with 5.251 new cases were diagnosed in 2011 alone, and this upward trend is expected to continue. There are two types of endometrial cancer: estrogen- related type I (approximately 80% of the cases) and unrelated to estrogen type II. Type I includes adenocarcinomas which grow slowly, have better prognosis, superficially infiltrate the myometrium, originate from endometrial hyperplasia without atypia, and occur before and after menopause. The most common type I mutations include PTEN, KRAS and microsatellite instability. Type II is represented by serous, mucinous, clear-cell carcinomas, with aggressive behavior associated with poor prognosis, high risk of distant metastases at diagnosis, deeper infiltration of the uterine muscle, often to serosa, originating from the atrophic endometrium, and typically presenting after menopause. The most common type II mutations include TP53, HER-2 and P16.

What Do We Know Now about IgE-Mediated Wheat Allergy in Children?

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

Food IgG4 antibodies are elevated not only in children with wheat allergy but also in children with gastrointestinal diseases.

BACKGROUND: Food sIgG and sIgG4 are highly individually versatile. We put a hypothesis that one of the responsible factors is the presence of gastrointestinal inflammatory diseases. The objectives were: 1. An analysis of wheat and rice sIgG and sIgG4 in healthy children, children with IgE-mediated wheat allergy (WA), coeliac disease (CD) and Helicobacter pylori infection (HP). 2. Usability of wheat sIgG and sIgG4 in the WA diagnostics. METHODS: We compared 388 each wheat and rice sIgG and sIgG4 in a group of 200 children: 50 WA (diagnosis, diet treatment, tolerance), 50 CD (diagnosis and remission), 50 HP and 50 healthy. SIgE, sIgG, sIgG4 were determined with the FEIA method (Pharmacia CAP System). RESULTS: In healthy children food sIgG were the lowest; no sIgG4 were found. In the CD diagnosis group wheat and rice sIgG and rice sIgG4 were the most common and their concentrations were the highest (p < .001, p < .05). Wheat sIgG4 were the highest in WA children (diagnosis and tolerance) to fall during the elimination diet (p < .05). Wheat and rice sIgG remained the same in all allergy phases. Rice sIgG also did not differ in the class G4. CONCLUSIONS: 1. Serum concentrations of wheat and rice sIgG and sIgG4 are elevated in children with CD, HP and WA. 2. Sub-clinical incidence of some gastrointestinal inflammatory diseases may be responsible for high individual versatility of food sIgG and sIgG4 concentrations in serum. 3. Wheat sIgG and sIgG4 in children do not correlate with WA clinical picture.

The natural history of IgE mediated wheat allergy in children with dominant gastrointestinal symptoms.

BACKGROUND: Wheat is one of the most common food allergens in children. The purpose of this study is to define the natural course of wheat allergy in children with dominant gastrointestinal symptoms and identify factors that help predict development of tolerance. METHODS: The prospective analysis covered 50 children with positive food challenge results (DBPCFC) and positive wheat IgE test result. Resolution of wheat allergy was determined on the basis of food challenge results (open challenge). The impact of each of the studied factors on the age when tolerance developed was assessed by means of the Cox proportional hazard regression model. RESULTS: The median age of tolerance development was 69.5 months (37-192 mo.). The rates of resolution were 20% by the age of 4 years, 52% by the age of 8 years, and 66% by 12 years, and 76% by 18 years. The median age of the tolerance development in children with peak wheat IgE level below10 kU/L was 41.4 months, with peak wheat IgE from 10 to 19.9 kU/L was 44.5 months, with peak IgE from 20 to 49.9 kU/L - 84,9 months and with peak IgE ≥ 50 kU/L - 190.5 months. The median of the age when the highest levels of IgE for wheat were reached was 33 months (2-52 mo.) in children with resolved wheat allergy and 67 months (36-178 mo.) in children with persistent allergy (p = .001). CONCLUSIONS: 1. The majority of children with wheat allergy can tolerate wheat by adolescence. 2. The age when tolerance to wheat developed depended on the level and the age of reaching the highest levels of specific IgE for wheat. The higher the values of the above parameters, the older a child was when they developed tolerance to wheat.