Evaluation of Prostate-Specific Membrane Antigen (PSMA) Immunohistochemical Expression in Early-Stage Breast Cancer Subtypes.

Breast cancer, known for its diverse subtypes, ranks as one of the leading causes of cancer-related deaths. Prostate-specific membrane antigen (PSMA), primarily associated with prostate cancer, has also been identified in breast cancer, though its role remains unclear. This study aimed to evaluate PSMA expression across different subtypes of early-stage breast cancer and investigate its correlation with clinicopathological factors. This retrospective study included 98 breast cancer cases. PSMA expression was examined in both tumor cells and tumor-associated blood vessels. The analysis revealed PSMA expression in tumor-associated blood vessels in 88 cases and in tumor cells in 75 cases. Ki67 expression correlated positively with PSMA expression in blood vessels (p < 0.0001, RSpearman 0.42) and tumor cells (p = 0.010, RSpearman 0.26). The estrogen and progesterone receptor expression correlated negatively with PSMA levels in blood vessels (p = 0.0053, R Spearman -0.26 and p = 0.00026, R Spearman -0.347, respectively). Human epidermal growth factor receptor 2 (HER2) status did not significantly impact PSMA expression. We did not detect any statistically significant differences between breast cancer subtypes. These findings provide evidence for a heterogenous PSMA expression in breast cancer tissue and suggest its correlation with tumor aggressiveness. Despite the limited sample size, the study provides valuable insights into the potential of PSMA as a prognostic, diagnostic, and therapeutic target in the management of breast cancer.

Analysis of Expression of the ANG1, CaSR and FAK Proteins in Uterine Fibroids.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

Autoimmune Thyroiditis Induced by Bartonella henselae (Cat-Scratch Disease) Might Be Reversible.

INTRODUCTION: Bartonella henselae infection leads to development of cat-scratch disease (CSD) but may also trigger of autoimmune thyroiditis (AIT). CASE PRESENTATION: We describe a 4-year-old boy with a severe fever of unknown etiology, disseminated neck lymphadenopathy, and a headache. Treatment with antibiotics was employed, but finally a left tonsillectomy, selective left lymphadenectomy, and immunophenotyping were performed to exclude lymphoma. Histologic examination excluded lymphoma but revealed CSD. IgG against B. henselae and Bartonella quintana was positive. A goiter was also found and positive anti-thyroid antibodies confirmed AIT. Two months later, the thyroid was not palpable, normal on ultrasound, and both anti-thyroid antibodies were negative. The full reversibility was documented, and 6-year follow-up showed that the patient remains disease free. CONCLUSION: This is the first report that AIT triggered by B. henselae/B. qunitana might be reversible if the pathogenetic factor is eliminated at an early stage of disease.

Calcium carbonate-enriched pumpkin affects calcium status in ovariectomized rats.

Calcium carbonate (CaCO3)-enriched pumpkin may serve as a good source of calcium for patients diagnosed with osteoporosis. In this study, we aimed to determine the effect of CaCO3-enriched pumpkin on Ca status in ovariectomized rats. The study included 40 female Wistar rats divided into five groups (n = 8). One group was fed with a standard diet (control group), while the other four groups were ovariectomized and received a standard diet (control ovariectomized group), or a diet containing CaCO3-enriched pumpkin, alendronate, or both. The nutritional intervention lasted 12 weeks, and then the rats were euthanized. Tissue and blood samples were collected and assessed for the levels of total Ca, estradiol, parathyroid hormone, and procollagen type I N propeptide. In addition, a histological analysis was performed on femurs. The results of the study suggest that CaCO3-enriched pumpkin can increase Ca content in femurs and improve bone recovery in ovariectomized rats. Furthermore, enriched pumpkin contributes to Ca accumulation in the kidneys, and this effect is more pronounced in combination with alendronate.

Peripheral T-Cell Lymphoma Possibly Due to Unrecognized Celiac Disease in an Elderly Patient: A Case Report.

Celiac disease (CD) is widely perceived as a childhood disorder. However, it has been demonstrated that 19-34% of new CD cases are diagnosed in patients over 60 years of age and lack the typical presentation. A 76-year-old female was admitted to the clinic due to a recurrent fever that had lasted over a year accompanied by progressive weakness, weight loss of about 10 kg, dehydration, and malnutrition. The patient had undergone resection of a fragment of the small intestine due to perforation and abscess 13 years previously (at which time no histopathological examinations were performed). During the current hospitalization, despite extensive laboratory, microbiological, and imaging tests, no specific diagnosis was made. Symptomatic treatment and empirical antibiotic therapy were conducted, but the patient died on the twenty-seventh day of hospitalization due to progressive respiratory failure. The autopsy revealed peripheral T-cell lymphoma in the mesentery of the small intestine, uterus, cecum, lung, and mediastinal lymph nodes. Based on the clinical picture, we believe that the lymphoma was induced by long-term, undiagnosed CD. Current knowledge allows us to see age-related differences in the manifestation of celiac disease and to be alert to the possible late-stage complications of the disease. The lack of awareness of how CD's symptoms vary with age may lead to misdiagnosis and serious consequences of delayed diagnosis, including death.

Myoepithelioma of bone: ultrastructural, immunohistochemical and molecular study of three cases.

Primary intraosseous myoepithelial tumors are rare neoplasms with only a handful of cases described in the medical literature. To date, intraosseous variant of benign myoepithelioma, due to its rarity, has not been studied ultrastructurally, and only one case of a malignant intraosseous myoepithelioma has been described. Three cases were retrieved from the files at the Massachusetts General Hospital (MGH). A diagnosis of benign myoepithelioma was made in case 1 and malignant epithelioma in cases 2 and 3. Ultrastructurally, intermediate filaments (without dense bodies) were found in each case with an abundance in case 1 and lesser amounts in cases 2 and 3. Surprisingly, cell junctions were not identified in case 1. However, they were found occasionally as intermediate junctions in case 2 and were easily identified as desmosome like junctions in case 3. The nucleus was irregular in the neoplastic cells of benign myoepithelioma which contrasted with cases 2 and 3 where the nuclei were oval yet had visible nucleoli. Herein, we add three new cases, including two new cases of malignant myoepithelioma. We also provide the first ultrastructural description of benign myoepithelioma of bone.

Rhabdomyosarcoma in children - current pathologic and molecular classification.

The last 25 years have brought significant progress in the treatment of sarcomas in children, especially rhabdomyosarcoma (RMS). Nevertheless, treatment failure in some patients results from considerable biological heterogeneity noted in these tumours. RMS, the most common malignant soft tissue neoplasm in children, includes two main subtypes: embryonal (ERMS) and alveolar (ARMS). Due to greater aggressiveness and worse prognosis of ARMS in comparison to ERMS, discrimination between different rhabdomyosarcoma subtypes is of crucial clinical importance. This paper presents the current histological classification of RMS, up-to-date immunohistochemical and biological research regarding RMS, and its associated clinical and prognostic significance.

Myeloid sarcoma in children - diagnostic and therapeutic difficulties.

Myeloid sarcoma (MS) is a malignant extramedullary tumour, which consists of immature cells of myeloid origin. It may occur de novo, concurrently or precede the diagnosis of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myeloid leukemia (CML). MS can also be a manifestation of the relapse of the disease. The more frequent sites of involvement are the skin, orbit, bone, periosteum, lymph nodes, gastrointestinal tract, soft tissue, central nervous system and testis. Because of its different localization and symptoms, and the lack of diagnostics algorithm, myeloid sarcoma is a real diagnostic challenge, in particular in patients without initial bone marrow involvement. The correct diagnosis of MS is important for adequate therapy, which is often delayed because of a high misdiagnosis rate. In the paper, the role of immunohistochemistry, cytogenetic and molecular genetic analyses is emphasized as well as the breadth of unclear aspects of this disorder in children.

Expression of semaphorin 3A (SEMA3A) in breast cancer subtypes.

Breast cancer is a major health concern, and its accurate diagnosis and management depend on identifying its histological type and biological subtype. Semaphorin-3A (SEMA3A) is a membrane protein with diverse roles in cellular processes, including cancer progression and angiogenesis regulation. However, its role in breast cancer remains poorly understood. This study aimed to evaluate SEMA3A expression in breast cancer and investigate its distribution across breast cancer subtypes: luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). Immunohistochemical evaluation was performed on 98 breast cancer patients' tumor specimens, and SEMA3A expression was assessed in tumor cells and vessels. The study included the analysis of the Ki67 proliferation index, estrogen receptor (ER) expression, progesterone receptor (PR) expression, and HER2 status in conjunction with SEMA3A expression. Analysis indicated positive expression of SEMA3A in breast cancer cells in 60 out of 98 cases. SEMA3A expression correlated positively with Ki67 levels in tumor cells (p = 0.0005, R Spearman 0.338). Notably, a negative correlation was found between SEMA3A expression and ER and PR levels in tumor cells (p = 0.04, Spearman's R = - 0.21 and p = 0.016, Spearman's R = - 0.25 respectively). HER2 status did not significantly influence SEMA3A expression. The study demonstrated positive SEMA3A expression in tumor vessels across all subtypes in 91 out of 98 cases, suggesting its involvement in endothelial cell function. However, no significant differences in SEMA3A expression were observed between breast cancer subtypes either in vessels or tumor cells. These findings suggest that elevated SEMA3A expression may be associated with worse prognosis in breast cancer, especially in ER- and PR-negative tumors. Further investigations are warranted to fully comprehend the role of SEMA3A in breast cancer biology, which may lead to the identification of novel therapeutic targets and personalized treatment strategies for breast cancer patients.

Cardiac solitary fibrous tumor - an extremely rare but potentially fatal diagnosis.

The background of this review is a description of the case of a 28-year-old man with an extremely rare cardiac solitary fibrous tumor (SFT). Although this tumor was removed surgically and in the 6-month follow-up examination no relapse was noted, recurrence was observed and confirmed in the magnetic resonance imaging 4 months later. SFT prevalence, symptoms and signs, treatment options and prognosis are reviewed.

Calcium-Deficit Diet Improves Iron Content in Ovariectomized Rats.

In women, menopause is associated with disorders related to calcium and iron content, which may increase the risk of osteoporosis. This study aimed to determine the effect of calcium deficiency on the iron content in ovariectomized rats. This study included 30 3-month-old female rats, which were divided into three groups: group C (n = 10)-control group fed the standard diet; group O-ovariectomized rats fed the standard diet; and group D-ovariectomized rats fed the calcium-deficit diet. After 3 months of experimental intervention, the weight of the rats was measured, and blood and tissue samples were collected. Morphological parameters were analyzed in whole blood, and serum levels of leptin, estrogen and C-reactive protein, and total antioxidant status were determined. The iron content was measured in tissues, and histological analysis was performed in the femur. The results obtained demonstrated that ovariectomy significantly decreased the iron content in bones, hair, spleen, liver, and kidneys. The calcium-deficit diet increased the iron content in tissues and the hemoglobin level in ovariectomized rats and also enhanced the number of osteoblasts in bones compared with the O group. In conclusion, calcium deficiency improved the iron content in ovariectomized rats in this 12-week study.

Influence of Isoflavones and Probiotics on Magnesium Status in Healthy Female Rats.

Isoflavones and probiotics are promising nutrients for bone health, and magnesium (Mg) is essential for bone metabolism. This study aimed to determine the effects of daidzein, genistein and Lactobacillus acidophilus on the Mg status of healthy female rats. Forty-eight rats were randomly assigned to six groups, with the control group receiving a standard diet (AIN 93M). The remaining groups were fed the same diet with added ingredients such as tempeh flour; soy flour; pure daidzein and genistein; L. acidophilus or a combination of daidzein, genistein, and L. acidophilus. Tissue samples were collected after the eight-week intervention, and Mg concentrations were analysed using flame atomic absorption spectrometry. Myeloid and erythroid cells were determined using the haematoxylin and eosin bone staining method. Statistical analyses were conducted using one-way ANOVA with Tukey's post hoc test and Pearson's correlation coefficient. The threshold for significance was p < 0.05. Compared with the control group, adding tempeh to the diet of rats resulted in significant changes in Mg concentrations in various tissues, with a decrease in the kidneys and an increase in the fur. Although not statistically significant compared to the control group, the tempeh group showed increased Mg concentrations in the femur and spleen. The myeloid-to-erythroid cell ratio did not differ significantly among groups, but all intervention groups showed higher ratios than the control group. A strong negative correlation was observed between Mg concentrations in the kidneys and fur. Conversely, a positive correlation was identified between Mg concentrations in the pancreas and fur. Daily consumption of tempeh may improve Mg status in the organism. Intake of pure daidzein, genistein, or probiotic seems to have no effect on Mg concentrations in healthy rats.

Molecular alterations of driver genes in non-small cell lung cancer: from diagnostics to targeted therapy.

Lung cancer is the leading cause of cancer death all over the world. The majority (80-85 %) of lung cancer cases are classified as non-small cell lung cancer (NSCLC). Within NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the most often recognized. The histological and immunohistochemical examination of NSCLC is a basic diagnostic tool, but insufficient for comprehensive therapeutic decisions. In some NSCLC patients, mainly adenocarcinoma, molecular alterations in driver genes, like EGFR, KRAS, HER2, ALK, MET, BRAF, RET, ROS1, and NTRK are recognized. The frequency of some of those changes is different depending on race, and between smokers and non-smokers. The molecular diagnostics of NSCLC using modern methods, like next-generation sequencing, is essential in estimating targeted, personalized therapy. In recent years, a breakthrough in understanding the importance of molecular studies for the precise treatment of NSCLC has been observed. Many new drugs were approved, including tyrosine kinase and immune checkpoint inhibitors. Clinical trials testing novel molecules like miRNAs and trials with CAR-T cells (chimeric antigen receptor - T cells) dedicated to NSCLC patients are ongoing.

Isoflavones and probiotics effect on bone calcium and bone cells in rats.

Isoflavones and probiotics have shown the therapeutic potential to alter calcium absorption and bone cell metabolism. This study sought to ascertain the effect of isoflavones and probiotics on calcium status and bone health in healthy female rats. Forty-eight adult female Wistar rats were grouped and fed: a standard diet (control); and standard diets with tempeh; soy; daidzein and genistein; Lactobacillus acidophilus; and a combination of daidzein, genistein, and L. acidophilus. The biochemical serum parameters, such as alanine transaminase, aspartate transaminase, glucose, and triacylglycerol concentrations, were measured, and calcium contents in tissues were determined. After staining the bone with hematoxylin and eosin, the number of osteoblasts, osteocytes, and the percentage of bone marrow adipocytes were counted. Compared with the control group, the soy group showed a significantly lower triacylglycerol concentration. The L. acidophilus group considerably increased the calcium content in the femoral bone. The daidzein and genistein, L. acidophilus, and a combination of daidzein, genistein, and L. acidophilus groups showed significantly lower calcium contents in the heart and kidneys. The daidzein and genistein group significantly enhanced the number of osteoblasts and osteocytes. A substantial inverse correlation was observed between calcium contents in kidneys and osteoblasts. In conclusion, the combination of daidzein, genistein, and L. acidophilus may improve bone calcium concentrations and bone cells. However, no synergistic effect between isoflavones and probiotics was detected in this study.

Corrigendum to "Isoflavones and probiotics effect on bone calcium and bone cells in rats" [Heliyon 9(6) (June 2023) e16801].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e16801.].

From KIT-mutated into wild-type: dedifferentiation of gastrointestinal stromal tumor in adolescent patient-a case report.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs from adult-type disease in terms of histopathology and molecular features. Case Description: We describe the management of the disease in a 10-year-old female patient diagnosed with a GIST of the stomach. In total, she has undergone successively total tumor resection, unsuccessful imatinib treatment and subtotal gastric resection at relapse. The first genetic test from primary tumor confirmed KIT mutations in exons 13 and 17, while the repeated genetic screening using tumor sample from subtotal gastric resection revealed no KIT or platelet-derived growth factor receptor α (PDGFRA) genes mutations. Such dedifferentiation from adult type (thus KIT-mutated) into wild-type (without KIT or PDGFRA mutation) has not been reported so far to the best of our knowledge. Currently, the patient is observed, and no further pharmacological nor surgical treatment has been administered. Conclusions: The case underlines the importance of genetic profiling combined with non-standard diagnostics (both histopathological and radiological) due to the treatment efficacy prediction. We moreover emphasize the necessity to create worldwide standards on the diagnostics and treatment of GIST in pediatric patients that would include options of targeted therapies.

Proteogenomic insights suggest druggable pathways in endometrial carcinoma.

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of ß-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

Underestimation of cancer in case of diagnosis of atypical ductal hyperplasia (ADH) by vacuum assisted core needle biopsy.

BACKGROUND: With the introduction of mammography screening, we are more often dealing with the diagnosis of precancerous and preinvasive breast lesions. An increasing number of patients are observed to show a premalignant change of ADH (atypical ductal hyperplasia). It also involves a wider use of the vacuum assisted core biopsy as a tool for verifying nonpalpable changes identified by mammography. AIM: This paper describes our experience of 134 cases of ADH diagnosed at Mammotome(®) vacuum core needle biopsy. MATERIAL AND METHODS: Of 4326 mammotomic biopsies performed at our institution in 2000-2006, ADH was diagnosed in 134 patients (3.1%). Patients underwent surgery to remove the suspected lesion. All histopathological blocks were again reviewed by one pathologist. Clinical, radiological and pathological data were collected for statistical evaluation. RESULTS: Underestimation of invasive changes occurred in 12 patients (9%). The only clinicopathologic feature of statistical significance radiologically and pathologically was the presence of radial scar in the mammography. CONCLUSIONS: More frequent diagnosis of precancerous changes in the mammotomic breast biopsy forces us to establish a clear clinical practice. The problem is the underestimation of invasive changes. The occurrence of radial scar on mammography for diagnosis of the presence of ADH increases the risk of invasive changes.

Controversies in the diagnosis and treatment of periampullary tumours.

Most tumours in the head of the pancreas are adenocarcinomas of the exocrine pancreas. However, carcinomas located in the head of the pancreas may originate from the papilla of Vater, the distal part of the common bile duct, or the duodenum. Tumours of that region, within 2 cm of the greater duodenal papilla, have been usually described as periampullary neoplasms. Adenocarcinomas separated from the major duodenal papilla and located in the major pancreatic duct, common bile duct, or duodenum are identified as ductal pancreatic carcinomas, distal bile duct cholangiocarcinomas or duodenal carcinomas. Surgical treatment is the only chance for cure. Pancreatoduodenectomy is the procedure of choice. Regional lymphadenectomy and removal of at least 16 lymph nodes are necessary for optimal long-term outcomes. Indications for adjuvant chemotherapy remain controversial. This review evaluates the available data on the pathological assessment of periampullary tumours and discusses the controversies of therapeutic management, emphasising adjuvant treatment.