The diagnosis of celiac disease (CD) at the first diagnostic step requires the detection of specific class A antibodies to tissue transglutaminase type-2 (TG2 IgA) and the measurement of total immunoglobulin A (tIgA) to exclude IgA deficiency. The aim of the study was to evaluate the new quantitative immunoassay panel allowing for the detection of celiac-specific antibodies with the simultaneous determination of tIgA from the same sample of blood at one time. This retrospective study included 104 pediatric patients divided into groups with recognized CD and IgA deficiency (n = 20; 19%), immunocompetent children with CD (n = 28; 27%), children with IgA deficiency and without CD (n = 28; 27%), and the control group of immunocompetent children without CD (n = 28; 27%). Intestinal biopsy with histopathological evaluation (except five patients with CD who were diagnosed without biopsy) and measurement of reference celiac specific antibodies were performed in all children. Multiparametric quantitative immunoassay Polycheck^® Celiac IgA plus total IgA test was used to evaluate its usefulness in CD screening and IgA deficiency diagnosis. The statistical analysis showed the high sensitivity and specificity of both TG2 IgA and tIgA on the multiparametric panel (sensitivity 96% and 100%; specificity 100% and 79%, respectively). The accuracy and area under the ROC curve for tIgA were 0.904 and 0.955, while for TG2 IgA they were 0.982 and 1.000, respectively. Although the sensitivity of IgA antibodies against deaminated gliadin peptides was low (20%), the specificity reached 100%. The study showed that Polycheck^® Celiac IgA plus total IgA test is a specific and sensitive tool for simultaneous serological CD screening and recognition of IgA deficiency.

To date, lateral differences of invasive breast cancer (IBrC) with respect to the angiogenic and hemostatic profiles were never studied. Here, we aimed to determine the relationship of tumor laterality with various clinical and pathological parameters including angiogenic and hemostatic profiles. A total of 92 women that were initially non-metastatic and treated by surgery were included in this single-center prospective study. Patients were grouped according to tumor localization. A four-year follow-up was accomplished in all patients with a 15.22% recurrence rate. An immunoassay of selected angiogenic and hemostatic parameters, as well as immunohistochemistry of estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki67, was comparatively performed in groups with right- and left-sided IBrC. The same analysis was carried out in a subgroup of patients with luminal A molecular subtype of cancer. Patients with right-sided tumors free of nodal involvement had a significantly longer overall survival compared to their left-sided counterparts (p = 0.0491). Additionally, right-sided tumors had a higher predisposition to be a luminal-A subtype of IBrC (p = 0.0016). Furthermore, 10% of left-sided tumors exhibited an overexpression of HER2, while only 2% patients suffering right-sided tumors displayed a positive score (p = 0.0357). Our findings revealed a significantly higher concentration of vascular endothelial growth factor (VEGF)-A (p = 0.0136), lower anti-angiogenic ratios (sVEGFR1/VEGF-A (p = 0.0208) and sVEGFR2/VEGF-A (p = 0.0068)), and elevated plasminogen activator inhibitor type 1 (PAI-1) (p = 0.0229) in patients with breast cancer localized in the left breast, regardless of the molecular subtype of IBrC. Our study showed that left-sided breast tumors without lymph node metastases demonstrate worse overall survival. Laterality of IBrC is associated with pro-angiogenic and pro-thrombotic conditions. We propose to consider laterality as a prognostic factor of IBrC.

Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival.

Neoangiogenesis is mediated by circulating bone marrow-derived endothelial progenitors (circulating EPCs). The aim of the study was the quantification of circulating EPCs from the peripheral blood mononuclear cells of invasive breast cancer (IBrC) patients by flow cytometry, before and after cancer adjuvant treatment. A total of 88 stage IA-IIB primary IBrC patients were enrolled prospectively. Circulating EPCs with the immune-phenotype CD45−CD34+CD133+CD31+ were assessed. Treatment significantly reduced the number of EPCs/µL in the general IBrC cohort. However, there was a relevant elevation in the number of circulating EPCs after nine months of adjuvant treatment in the group of patients aged ≥ 55 years, of T2 clinical type, with nodal involvement (N1) and Ki67 expression > 15%. Follow-up revealed a significantly higher incidence of disease relapse in breast cancer patients with low pre-treatment circulating EPCs levels compared with those with a high baseline circulating EPCs count. The receiver-operating characteristic curve identified a tumour diameter of 2.1 cm as the best cut-off value to discriminate between disease-relapse subjects and non-relapse disease cases. Our study strongly indicates that, next to tumour diameter and Ki67 expression, circulating bone marrow-derived EPCs may serve as useful markers for predicting therapeutic outcomes as well as a future prognosis.

Despite the advancements in breast cancer (BrC) diagnosis and treatment, a considerable proportion of patients with early-stage disease still experience local recurrence or metastasis. This study aimed to assess the levels of specific angiogenic parameters in the EDTA plasma of BrC patients before and after treatment and to explore their clinical and prognostic significance. The levels of vascular endothelial growth factor A (VEGF-A), soluble form of vascular endothelial growth factor receptor type 1 (sVEGFR1), and soluble form of vascular endothelial growth factor receptor type 2 (sVEGFR2) were measured in 84 early BrC patients, both prior to surgery and within a median time of nine months post-treatment. Prognostic significance was evaluated using Kaplan-Meier survival and Cox regression analyses. Linear regression models were employed to examine the independent impact of selected angiogenic factors on DFS in breast cancer patients. The results of uni- and multivariate analyses indicated that a pre-treatment concentration of sVEGFR1 above 30.99 pg/mL was associated with improved disease-free survival (DFS) (p < 0.0001 for both analyses), while a pre-treatment concentration of sVEGFR2 above 9475.67 pg/mL was associated with an increased risk of BrC relapse (p < 0.0001 for both analyses). Additionally, a post-treatment concentration of sVEGFR2 above 7361.71 pg/mL was associated with better overall survival (OS) based on the Kaplan-Meier survival analysis (p = 0.0141). Furthermore, linear regression models revealed a significant inverse association between pre-treatment levels of sVEGFR1 and the risk of relapse (standardized β −0.2578, p = 0.0499) and a significant positive association of VEGF-A levels with the risk of recurrence (standardized β 0.2958, p = 0.0308). In conclusion, the findings suggest that both pre- and post-treatment levels of sVEGFR1 and sVEGFR2 may hold promise as potential prognostic markers for BrC patients.