Fumarate hydratase deficient renal cell carcinoma (FHRCC) can exhibit a heterogenous immunoprofile. In the present case, a solitary 10.5 cm mixed cystic and solid left kidney tumor showed various growth patterns, involving renal sinus adipose tissue and the renal pelvis. Tumor cells showed prominent nucleoli and perinucleolar halos. Aberrant diffuse (>90%), strong, and membranous carbonic anhydrase 9 and variable GATA3 expression were present. Diagnostic loss of fumarate hydratase expression and 2-succinyl cysteine overexpression (cytoplasmic and nuclear) were identified. Carbonic anhydrase 9 and GATA3 expression in FHRCC is rarely reported in the literature, and may cause misdiagnosis of clear cell RCC and/or urothelial carcinoma.

Although substantial advances in the identification of cytogenomic subtypes of childhood acute lymphoblastic leukemia (ALL) have been made in recent decades, epidemiologic research characterizing the etiologic heterogeneity of ALL by subtype has not kept pace. The purpose of this review is to summarize the current literature concerning subtype-specific epidemiologic risk factor associations with ALL subtype defined by immunophenotype (e.g., B-cell vs. T-cell) and cytogenomics (including gross chromosomal events characterized by recurring numerical and structural abnormalities, along with cryptic balanced rearrangements, and focal gene deletions). In case-control analyses investigating nongenetic risk factors, home paint exposure is associated with hyperdiploid, MLL-rearranged, and ETV6-RUNX1 subtypes, yet there are few differences in risk factor associations between T- and B-ALL. Although the association between maternal smoking and ALL overall has been null, maternal smoking is associated with an increasing number of gene deletions among cases. GWAS-identified variants in ARID5B have been the most extensively studied and are strongly associated with hyperdiploid B-ALL. GATA3 single nucleotide variant rs3824662 shows a strong association with Ph-like ALL (OR = 3.14). However, there have been relatively few population-based studies of adequate sample size to uncover risk factors that may define etiologic heterogeneity between and within the currently defined cytogenomic ALL subtypes.

We present a case of synchronous renal cell carcinoma and urothelial carcinoma. Our case was a true collision tumor and both components were high grade. Metastasis to the adrenal gland by the urothelial carcinoma was observed. The morphologic impression was confirmed with GATA3 expression by the urothelial carcinoma component and PAX8 expression by the renal cell carcinoma component. We have reviewed the contemporary literature of this unusual dual diagnosis.

Asthma is among the most common chronic disorders of airways, which affects both children and adults. Asthma being a common disease among different segments of population, it has a high mortality rate and, in the absence of appropriate care, affects the quality of life and leads to economics losses. In a view of continuing growth in the incidence of asthma, it is important to find relevant biological targets for developing new approaches to astma therapy. Recent advances in molecular immunology, genetics, and bioinformatics allowed genes involved in the pathogenesis of asthma to be identified, which provided prerequisites for the development of new types of drugs that can regulate the activity of pathogenically significant genes. To date, a number of technologies for sequence-specific gene regulation (ASO, ribozymes, DNAzymes, EGS, DNA-decoys, U 1-adapters) are available, but RNA interference is the most promising approach in both terms of efficacy and financial cost. This review focuses on the generalization and analysis of experimental data regarding the use of RNA interference technology for the treatment of astma.

Vaginal Brenner tumor is extremely rare. Only five cases have been reported in the English literature to date. Here we report a vaginal Brenner tumor in a 76-year old postmenopausal woman, who presented with a 2.5cm-sized sessile vaginal polyp. Microscopically, it showed characteristic features of Brenner tumor consisting of three components; transitional islands, glands, and dense fibrous stroma. The epithelial tumor cells were positive for GATA-3, p63 and ER, but negative for PAX8. The origin of Brenner tumors in the vagina is unclear, but previous reports suggested of Müllerian origin. However, our case revealed that vaginal Walthard nests could be possible precursor lesions based on their immunohistochemical staining results.

The potential prognostic value of GATA binding protein 3 (GATA3) in breast cancer has recently increased, although the evidence is inconclusive. This meta-analysis of 10 articles involving 5,080 breast cancer patients explored the prognostic and clinicopathological value of GATA3 in breast cancer. Time to tumor progression (TTP) and overall survival (OS) were primary endpoints. Pooled hazard ratio (HR), pooled risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate the association between GATA3, prognosis, and clinicopathological parameters. High GATA3 expression predicts breast cancer, with a HR (HR = 0.671; 95% CI = 0.475-0.947; P = 0.023) of TTP, but is not associated with OS (HR = 0.889; 95% CI = 0.789-1.001; P = 0.052). GATA3 overexpression is associated with positive ER (RR = 3.155; 95% CI = 1.680-5.923; P = 0.000), positive PR (RR = 3.949; 95% CI = 1.567-9.954, P = 0.004), lower nuclear grade (RR = 0.435; 95% CI = 0.369-0.514; P = 0.000), and smaller tumor size (RR = 0.816; 95% CI = 0.709-0.940; P = 0.005). High GATA3 expression may predict TTP in breast cancer, and such patients may show better clinicopathological features.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), corresponds with a heterogeneous group of mature T-cell lymphomas. Recent gene expression profiling studies have identified at least two molecular subgroups (GATA3 and TBX2). Standard treatment and outcomes remain poor. High-dose chemotherapy with autologous stem cell transplantation is incorporated into primary therapy for young fit patients but remains ineffective for most and has not been tested in a randomized study. Several novel agents have been approved for use in relapsed/refractory PTCLs, and although response rates are modest for most, durable remissions have been reported. Selecting rationale combinations and incorporating predictive biomarkers will be important moving forward to improve outcomes in patients with PTCL.

We report the case of a 43-year-old woman, who was admitted for intense pelvic pains. Biological investigations showed an increase of β-HCG level. The abdomino-pelvic computed tomography revealed a voluminous mass infiltrating the bladder. A transurethral resection was performed. The histopathological examination evidenced an invasion of the bladder by a massive carcinomatous proliferation composed of clear epithelial cells with in some places syncytiotrophoblastic cells and rarely cytotrophoblastic cells. Immunohistochemical analyses revealed a staining of GATA-3 by the two components, an expression of p63 by the clear cell urothelial component and the immunoreactivity of β-HCG by the trophoblastic component. Ki-67 labeling index was very high. The diagnosis of mixt urothelial carcinoma with clear cells and trophoblastic differentiation was proposed. This is a rare difficult histopathological diagnosis which should be known by pathologists. It is correlated to a poor clinical outcome with a high tendency to lymph node or visceral metastases.

GATA3 is a zinc-binding transcription factor that regulates the differentiation of many human tissue types, including the mammary gland. In surgical pathology, immunohistochemistry for GATA3 is largely used to support urothelial or breast origin in a carcinoma of unknown origin. GATA3 is sensitive but not entirely specific in this setting. Although GATA3 labeling is highest in estrogen receptor-positive carcinomas, it also labels estrogen receptor-negative carcinomas and thus has particular diagnostic utility in the setting of triple-negative breast carcinomas, which are typically negative for other mammary-specific markers.

OBJECTIVE: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a severe autoimmune disease that is caused by regulatory T cell deficiency due to FOXP3 gene mutations. The long-term outcome can be variable depending on the extent of tissue damage caused by autoimmunity and infections, the use of immunosuppressive treatment or sequela of bone marrow transplantation.
METHODS: We used immunohistochemical staining to analyze cell types infiltrating the tissue of affected organs from a classic IPEX patient with a splicing mutation (c.736-2A>C) in the FOXP3 gene. Expression of transcription factors that are critical for immune responses including T-bet, GATA-3, RORγt, and FOXP3 were evaluated in various tissue samples. For objective analysis of the distribution of different cell types in tissues, we used an automated microscope-based image acquiring system to assess quantitatively the different cell types by investigating the histopathological changes in the patient\'s biopsy samples obtained from the intestine and the kidneys before and after treatment.
RESULTS: The percentages of cells expressing the TH2-associated transcription factor GATA3 were higher in the IPEX patient before treatment than in controls, suggesting that TH2-type cells contribute to the tissue inflammation of the gut and kidneys in IPEX syndrome. Immunosuppressive treatment effectively decreased the number of effector cells in the kidneys and intestine of the IPEX patient.
CONCLUSIONS: This study provides quantitative evidence that the inflamed intestinal and renal tissues of the IPEX patient contain TH2-type immune effector cells, which decreased in number after immunosuppressive treatment was initiated and the clinical symptoms had improved.