GATA Binding Protein 3 (GATA-3) expression evaluation as prognostic factor in breast cancer and its relationship with other immunemarkers

Introduction: Breast cancer is the most frequent cancer in which the mortality rate could be decreased by proper management. The GATA3 transcription factor is one of the most frequently mutated genes in breast cancer. Materials and Methods: We studied the immunohistochemical (IHC) expression of estrogen and progesterone receptor, human epidermal growth factor receptor 2, and GATA-3 in 166 radical/partial mastectomy specimens having different histologic grades and stages of breast carcinoma. All samples were obtained from the pathology department of Sina hospital in Tehran-Iran from 2010 to 2016. Results: There was a direct relationship between the luminal subtype carcinoma and higher GATA-3 expression (P-value: 0.001) and between triple-negative carcinoma and lower GATA-3 expression (P-value: 0.001). Moreover, there was a direct relationship between the metastasis rate and the tumor's grade with GATA-3 staining (P-value: 0.000 and 0.001, respectively). Conclusion: GATA-3 expression is related to the histopathologic and prognostic factors. GATA3 can be introduced as an important predictor in breast cancer patients.

GATA2 variants in patients with non-tuberculous mycobacterial or fungal infections without known immunodeficiencies

ABSTRACT Introduction Haploinsufficiency of the hematopoietic transcription factor GATA2 is associated with a broad spectrum of diseases, including infection susceptibility and neoplasms. We aimed to investigate GATA2 variants in patients with non-tuberculous mycobacterial (NTM) and/or fungal infections (FI) without known immunodeficiencies. Method We performed GATA2 genotyping in patients with NTM and/or FI. Results Twenty-two patients were enrolled (seventeen FI, four NTM and one with both infections). The pathogenic variant NG_029334.1:g.16287C>T was found in one patient (4.5%) and two asymptomatic offsprings. We also found the likely-benign variant NG_029334.1:g.12080G>A (rs2335052), the benign variant NG_029334.1:g.16225C>T (rs11708606) and the variant of uncertain significance NG_029334.1:g.16201G>A (rs369850507) in 18.2%, 27.3%, and 4.5% of the cases, respectively. Malignant diseases were additionally diagnosed in six patients. Conclusion Although detected in 45.4% of the patients, most GATA2 variants were benign or likely benign. Identifying a pathogenic variant was essential for driving both the patient's treatment and familial counseling. Pathogenic variants carriers should receive genetic counseling, subsequent infection prevention measures and malignancies surveillance. Additionally, case-control genotyping should be carried out in Brazil to investigate whether the observed variants may be associated with susceptibility to opportunistic infections and/or concurrent neoplasms.

Changes in percentage of GATA3+ regulatory T cells and their pathogenic roles in allergic rhinitis / 南方医科大学学报

OBJECTIVE@#To investigate the changes in percentage of GATA3+ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models.@*METHODS@#The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3+ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3+ Treg cells and the expressions of Th2 cytokines.@*RESULTS@#Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3+ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3+ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05).@*CONCLUSION@#The percentage of GATA3+ Treg cells is decreased in AR patients and mouse models. GATA3+ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3+ Treg cells as a new therapeutic target for AR.

Clinical characteristics and genetic analysis of a child with specific type of diabetes mellitus caused by missense mutation of GATA6 gene / 浙江大学学报·医学版

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m2 (P10-P15)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.

Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.

The role of NLRP3/GATA-4/VEGF signal pathway in neovascular age-related macular degeneration / 中国医师杂志

Objective:To explore the potential role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/GATA-binding protein 4 (GATA-4)/vascular endothelial growth factor (VEGF) signal pathway in neovascular age-related macular degeneration (nAMD).Methods:We applied the TRANSFAC Public database to search the human and mouse VEGF promoters and upstream transcription factors, analyzed the transcription factors that may influence the transcriptional activity of VEGF. The RAW264.7 cells were divided into control group and lipopolysaccharide (LPS) stimulated group (LPS group). Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the activation of NLRP3 inflammasome, and the mRNA levels of GATA-4 and VEGFA. Thus, we applied the specific small molecular NLRP3 inhibitor MCC950 pretreated RAW264.7 cells (LPS+ MCC950 group), and detected the gene expression of NLRP3, Caspase-1, interleukin 1β( IL-1β), GATA-4 and VEGFA.Results:There were multiple GATA transcription factor binding sites upstream of human and mouse VEGF promoters. Compared with the control group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS group were increased (all P<0.05). Compared with LPS group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS+ MCC950 group were significantly decreased (all P<0.05). Conclusions:NLRP3/GATA-4/VEGF signal pathway may play a significant role in the pathologic processes of nAMD.

Hematopoietic regulation of transcription factor GATA1 and mutations causing hereditary erythroid and megakaryocytic disorders / 中国输血杂志

GATA-binding protein 1 (GATA1), an important hematopoietic transcription factor, specifically regulates the proliferation and differentiation of erythroid and megakaryoid cells at the transcription level, which maintains the normal development and maturation of these two lineages. The functional structure of GATA1 is composed of one N-terminal transactivation domain (N-TAD) and two zinc fingers (NF and CF). GATA1 is highly conserved in different species. Alteration of GATA1 expression or function will lead to transcriptional disorder of erythrocyte and megakaryocyte related genes, resulting in various clinical phenotypes. This article reviews the molecular structure of GATA1, its transcriptional regulation in erythrocyte and megakaryocyte, and the hereditary hematopoietic regulatory disorders of these two lineages caused by GATA1 mutations.

Intraventricular metastasis from carcinoma breast masquerading as choroid plexus neoplasm: A case report

Metastatic tumors in the brain represent the most common type of intracranial neoplasm, comprising 8–10% of all brain tumors. 30% of such tumors are primarily of breast origin in females. Brain parenchymal metastasis is the more common presentation. Intraventricular spread is rare, seen in less than 5% of cases in a metastatic scenario. Here, we report a case of 41-year-old female presenting with intraventricular brain metastasis in a follow-up case of carcinoma breast. Five years post-surgery, the patient presented with complaints of headache. On evaluation, magnetic resonance imaging (MRI) brain showed an intraventricular lesion in the fourth ventricle. She was operated on for the same and the biopsy revealed a tumor with a complex papillary pattern resembling choroid plexus papilloma. On immunohistochemistry (IHC), the tumor cells were positive for cytokeratin 7 (CK7), Epithelial membrane antigen (EMA), GATA3, and mammaglobin favoring a metastasis from breast origin. Hence, a possibility of brain metastasis should be kept in mind in patients presenting with solitary ventricular masses due to the lack of definite radiological characteristics in such locations and histological overlap. Also, organ-specific IHC is a must in today's evidence-based era as is reflected in our case.

”TAM”ing of the shrew-challenges in the diagnosis of Neonatal leukemia with Down's syndrome -A case report with literature review

The latest WHO (2017) classification describes the hematological abnormalities of Down's syndrome as a separate entity under 'Myeloid proliferations associated with Down's syndrome'. It includes Transient Abnormal Myelopoiesis and Myeloid leukemia of Down's syndrome. Here we report a case of a 3 days old neonate with Down's syndrome, presenting with a leukemic blood picture. The baby had icterus, fever and hepatosplenomagaly. Peripheral blood showed megakaryoblasts and giant platelets. A diagnosis of transient abnormal myelopoiesis was made by confirming with karyotyping and immunophenotyping. We attempt to address all the diagnostic challenges faced by a clinician and pathologist same, upon encountering such a case,by following an algorithmic approach. The mandatory need for follow up and cytogenetic studies in identifying high risk cases that will become myeloid leukemia of Down's syndrome are stressed. Our case also throws light upon the significance of identification of GATA1 mutation in diagnosing and prognostication of such cases.

Cauda Equina Compression an Ayurvedic management w.r.s to Gridrasi and Pakwasaya Gata Vata

Cauda equina compression at the level of L4/L5 or L5/S1 level is a surgical emergency with potentially significant consequences, including motor and sensory dysfunction. The causes include disc herniation, spinal stenosis, cancer, trauma, epidural abscess. The common cause is usually a disc herniation which is most commonly due to trauma, age, connective tissue disorders and congenital disorders. Cauda equina syndrome a disorder caused by compression of the nerve roots in the cauda equina region. This can cause permanent loss of bladder and bowel control if not treated within time. The incidence of a herniated disc is about 5 to 20 cases per 1000 adults annually and is most common in people in their third to the fifth decade of life with a male to female ratio 2:1. If decompressive surgery is delayed, there can be catastrophic consequences for the patient in terms of bladder, bowel and sexual function. In the present case study, a 36 year old female patient who was diagnosed as a case of Cauda Equina compression due to an extruded L4-L5 disc refused to undergo surgery and opted for Ayurvedic treatment. She was admitted in the Kayachikitsa IPD for 45 days. She was treated with the principle of Gridrasi along with Pakwasayagata vata. Deepana pachana and Vasti or Sodhana is the main treatment choice. Rooksha and Snigdha swedas were done which also help to reduce the stiffness and pain. After the management her physical condition and quality of life improved.

Metastasis of mucinous breast carcinoma to the lower alveolus as initial presentation: a diagnostic dilemma

ABSTRACT Metastases in the oral cavity are rare and comprise approximately 1% of all oral malignancies. They usually involve the jaws but may also be found in the soft tissues and salivary glands. Women's most common metastatic malignancies are from primary breast cancers. However, metastasis of mucinous breast carcinoma to the lower alveolus mimicking an aggressive primary malignancy as the initial presentation is exceptionally uncommon. We describe the case of a 66-year-old lady with an ulceroproliferative growth in the right lower alveolus. The lesion eroded the mandible and involved the adjacent soft tissues with no prior history of lesion anywhere else. The lesion clinically mimicked a squamous cell carcinoma and masqueraded as a salivary gland mucinous adenocarcinoma on histopathology. The possibility of a metastatic lesion from the breast rather than a primary of the alveolus was also entertained, aided by the immunohistochemical findings of positivity of the tumor cells for GATA3. A positron emission tomography (PET) scan was undertaken to ascertain the primary site. It detected a hypermetabolic lesion in the left breast, which biopsy revealed mucinous breast carcinoma on histopathological evaluation. Metastasis of breast mucinous carcinoma by the hematogenous route is extremely rare; very few cases have been reported. This case illustrates the diagnostic challenges such a lesion can pose to the surgeon and the pathologist. In the advent of such lesions being the initial clinical presentation, a vigilant clinicopathological and radiological assessment is essential to detect the primary.

Pulmonary Alveolar Proteinosis due to Familial Myelodysplastic Syndrome with resolution after stem cell transplant

ABSTRACT Pulmonary alveolar proteinosis (PAP) is a rare lung disease with an incidence of 0.2 cases per million. PAP has multiple causes, including autoimmune, hereditary, congenital, or secondary. The latter includes hematologic conditions and exposure to different kinds of dust. Most patients present fever, dyspnea, and cough. The chest computed tomography (CT) may reveal the crazy-paving polygonal shapes with superimposed ground glass opacities delimited by thickened interlobular septa; however, this finding is more prevalent in patients with autoimmune PAP. Bronchoalveolar lavage (BAL) shows a milky-opaque appearance with PAS-positive debris on cytology. Treatment is focused on the underlying disease; however, some patients may require whole lung lavage for symptomatic management. We report a case of a 30-year-old female with a history of familial myelodysplastic syndrome (MDS) with GATA 2 mutation who presented to the outpatient clinic with several months of progressive dyspnea and nonproductive cough. The chest CT revealed bilateral ground-glass opacities prominently in the upper lobes. She underwent a bronchoscopy with lavage and biopsy, which revealed fragments of lung parenchyma with intra-alveolar coarse granular eosinophilic material strongly positive for PAS and d-PAS. The overall clinical presentation and histologic findings were diagnostic of PAP. Her GM-CSF was negative, and due to her history of MDS, secondary PAP (S-PAP) was strongly suspected. She underwent a successful allogeneic bone marrow pluripotent stem cell transplant to treat the myelodysplastic syndrome, with a follow-up chest CT showing clear lung parenchyma. The patient had resolution of symptoms about four months after the bone marrow transplant, confirming the diagnosis of S-PAP.

Targeting GATA1 and p2x7r Locus Binding in Spinal Astrocytes Suppresses Chronic Visceral Pain by Promoting DNA Demethylation / 神经科学通报·英文版

Irritable bowel syndrome is a gastrointestinal disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that injury and inflammation during the neonatal period have long-term effects on tissue structure and function in the adult that may predispose to gastrointestinal diseases. In this study we aimed to investigate how the epigenetic regulation of DNA demethylation of the p2x7r locus guided by the transcription factor GATA binding protein 1 (GATA1) in spinal astrocytes affects chronic visceral pain in adult rats with neonatal colonic inflammation (NCI). The spinal GATA1 targeting to DNA demethylation of p2x7r locus in these rats was assessed by assessing GATA1 function with luciferase assay, chromatin immunoprecipitation, patch clamp, and interference in vitro and in vivo. In addition, a decoy oligodeoxynucleotide was designed and applied to determine the influence of GATA1 on the DNA methylation of a p2x7r CpG island. We showed that NCI caused the induction of GATA1, Ten-eleven translocation 3 (TET3), and purinergic receptors (P2X7Rs) in astrocytes of the spinal dorsal horn, and demonstrated that inhibiting these molecules markedly increased the pain threshold, inhibited the activation of astrocytes, and decreased the spinal sEPSC frequency. NCI also markedly demethylated the p2x7r locus in a manner dependent on the enhancement of both a GATA1-TET3 physical interaction and GATA1 binding at the p2x7r promoter. Importantly, we showed that demethylation of the p2x7r locus (and the attendant increase in P2X7R expression) was reversed upon knockdown of GATA1 or TET3 expression, and demonstrated that a decoy oligodeoxynucleotide that selectively blocked the GATA1 binding site increased the methylation of a CpG island in the p2x7r promoter. These results demonstrate that chronic visceral pain is mediated synergistically by GATA1 and TET3 via a DNA-demethylation mechanism that controls p2x7r transcription in spinal dorsal horn astrocytes, and provide a potential therapeutic strategy by targeting GATA1 and p2x7r locus binding.

Clinical Effect of Bushen Shengxue Prescription on Chronic Aplastic Anemia and Its Effect on T Cell Subsets and Expression of T-bet and GATA3 / 中国实验方剂学杂志

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ2=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ2=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ2=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4+， and CD4+/CD8+ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19-， HLA/DR+， and CD25+ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4+， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Whole-Exome Sequencing Reveals Pediatric Rare Syndromic Hearing Loss / 罕见病研究

  Objective  To discuss the significance of genetic diagnosis of children with syndromic hearing loss by using whole-exome sequencing.  Methods  The clinical data of 34 children with sensorineural hearing loss were collected and the whole exons of genome of the children and their parents were sequenced and analyzed.  Results  Genetic causative gene and mutations have been identified in 19 children, including 4 genes (HARS2, USH2A, GATA3, MITF) related to rare syndromic hearing loss. Fifteen children were diagnosed with non-syndromic hearing loss related gene, including 8 cases with GJB2 mutation, 5 cases with SLC26A4 mutation and 2 cases with MYO15A mutation. Mutations of c.435_437del(p.K147del) and c.1403G > C (p.G468A) in gene HARS2, c.11389+1del in gene USH2A, c.1327delA(p.M443Wfs*33) in gene GATA3, c.627C > A(p.C209X) in gene MITF and c.8033_8057delinsG(p.N2678_D2686delinsS) in gene MYO15A were first reported.  Conclusions  Whole-exome sequencing helps the accurate diagnosis of causes of hearing loss, especially for the rare syndromic hearing loss with atypical clinical manifestations. Information from genetic testing may highlight further recommended exams of structure and functions of related organs.

Clinical characteristics and molecular mechanisms of hypoparathyroidism related to GATA3 gene mutation / 中华内科杂志

Objective:To analyze the clinical characteristics and molecular mechanisms of 5 cases of hypoparathyroidism caused by GATA3 gene mutation.Methods:A total of 5 childhood-onset hypoparathyroidism patients with GATA3 mutation were identified from 198 hypoparathyroidism (aged ≤18 years) from 1975 to 2021 in Peking Union Medical College Hospital. Clinical data and biochemical indices of the 5 patients were collected and analyzed retrospectively. Genetic screening was conducted by targeted next-generation sequencing (T-NGS), and bioinformatics analysis was performed to analyze the underline mechanisms.Results:The medium onset age of hypoparathyroidism of the 5 patients was 0.5 (0.1, 1.3) years old, and the time duration from onset to confirmed diagnosis of hypoparathyroidism and hypoparathyroidism- deafness-renal dysplasia syndrome was (7.0±5.2) years and (15.0±5.4) years, respectively. The clinical manifestations included carpopedal spasm accompanied by seizures (5 cases), basal ganglia calcification (5 cases), cataract (1 case), deafness (4 cases), and renal malformations or absence (2 cases). The blood calcium and blood parathormone(PTH) before treatment was (1.65±0.31) mmol/L and (4.64±2.63) ng/L, respectively. The 5 patients carried different heterozygous mutations in GATA3 gene, which caused nonsense mutations, frameshift mutations and splice site mutations, respectively. All the GATA3 gene mutations of the 5 patients are classified as pathogenic or likely pathogenic by the Clin Var database and American College of Medical Genetics and Genomics(ACMG).Conclusions:Attention should be paid to genetic diseases in patients with childhood-onset hypoparathyroidism. The possibility of hypoparathyroidism-deafness-renal dysplasia syndrome should be considered in hypoparathyroidism patients with hearing loss or renal dysplasia. GATA3 gene screening is highly recommended for the confirmation of the diagnosis.

Expression of GATA binding protein 3 in non specific type invasive breast cancer and its relationship with prognosis of patients / 中国综合临床

Objective:To investigate the expression of GATA binding protein 3 (GATA-3) in non-specific type invasive breast cancer(IBC-NST) and its relationship with prognosis of patients.Methods:The clinical data of 98 patients with IBC-NST in Beijing Chuiyangliu Hospital from January 2013 to December 2017 were retrospectively analyzed. The normal tissues adjacent to the cancer were collected as the control group by case-control study. The expression of GATA-3 in cancer tissues and normal tissues adjacent to the cancer was detected by immunohistochemical method separately. The relationship between the different expression of GATA-3 and the clinical and pathological features and prognosis of IBC-NST was analyzed. In this study, the counting data were used χ 2 inspection. The survival rate was analyzed by Kaplan-Meier method and compared between groups by Long-rank method. Logistic regression was used for multivariate analysis. Results:The positive expression rate of GATA-3 was 61.2% (60/98) in cancer tissues and was 86.7% (85/98) in the normal tissues of IBC-NST. The difference was statistically significant (χ 2=16.57, P<0.001). There was no significant difference in the expression of GATA-3 between the patients with non special invasive breast cancer and the diameter of tumor (all P>0.05).There were significant differences in the expression of GATA-3 in histological grade, TNM stage, lymph node metastasis, ER, PR and HER2 (all P<0.05). Logistic regression analysis showed that lymph node metastasis ( OR=2.628, 95% CI 1.180-5.812, P=0.018), TNM staging ( OR=3.419,95% CI 1.067-7.565, P=0.041), histological grade ( OR=1.540,95% CI 1.026-2.361, P=0.044), and HER-2 positive expression ( OR=1.801,95% CI 1.067-3.221, P=0.048) were risk factors for GATA-3 negative expression. The 3-year disease-free survival rate of patients with GATA-3 positive expression was 80.0% and that of patients with GATA-3 negative expression was 57.9%. The difference between the two groups was statistically significant (χ 2=4.30, P=0.045). The 3-year survival rate of patients with GATA-3 positive expression (86.7%) was significantly higher than that of patients with GATA-3 negative expression (68.4%) and the difference was statistically significant (χ 2=3.99, P=0.046). Conclusion:Compared with the normal tissues adjacent to the cancer, the expression of GATA-3 was lost in cancer tissues of IBC-NST patients. TNM staging, histological grade, lymph node metastasis, ER, PR and HER-2 were related to the expression of GATA-3. The positive expression of GATA-3 suggest that the prognosis of patients was better. Lymph node metastasis, histological grade, TNM staging and HER-2 positive expression were the risk factors of GATA-3 negative expression.

Histopathological and immunohistochemical characteristics of malignant adenomyoepithelioma in a cat: case report / [Características histopatológicas e imuno-histoquímicas do adenomioepitelioma maligno em gata: relato de caso]

The malignant adenomyoepithelioma is a rare mammary tumor in women and uncommon in cats with only one report in this species. In this case report, the histopathological and immunohistochemical characteristics of six cases of malignant adenomyopithelioma in the feline mammary gland are described. Microscopic evaluation of tumors showed dense cellular neoplastic proliferation, composed of malignant myoepithelial and epithelial cells, formed by varied arrangements and presenting papillary, tubular and solid nest proliferation. Immunohistochemistry was performed for markers Ki67, Cox-2, RE, RP, p63 and HER-2. All cases were positive for p63, confirming the myoepithelial nature of neoplastic cells. The diagnosis of malignant adenomyopithelioma was made possible through the association between histopathological characteristics and immunohistochemical results.(AU)

O adenomioepitelioma maligno é uma neoplasia mamária rara em mulheres e incomum em gatas, possuindo apenas uma descrição nessa espécie. Neste relato de caso, são descritas as características histopatológicas e imuno-histoquímicas de seis casos de adenomioepitelioma maligno na glândula mamária felina. A avaliação microscópica dos tumores demonstrou proliferação neoplásica densamente celular, composta por células mioepiteliais e epiteliais malignas dispostas em padrão papilar, tubular e ninhos sólidos. Foi realizada técnica de imuno-histoquímica para os marcadores Ki67, Cox-2, RE, RP, p63 e HER-2. Todos os casos foram positivos para p63, confirmando a natureza mioepitelial das células neoplásicas. O diagnóstico de adenomioepitelioma maligno foi possível por meio da associação entre as características histopatológicas e os resultados de imuno-histoquímica.(AU)

Possible Common Origin of B Chromosomes in Neotropical Fish (Siluriformes, Auchenipteridae) Reinforced by Repetitive DNA Mapping

Abstract The aim of this paper was to present the second case of B chromosomes in Auchenipteridae (Trachelyopterus sp.), and to test the hypothesis that the B chromosomes of this species and Parauchenipterus galeatus might have a common origin, since these two species have phylogenetic proximity. Both species have 58 chromosomes in the A complement, heterochromatin preferentially located at terminal region of the most of chromosomes, simple Ag-NORs located at the short arm of a subtelocentric pair, which was confirmed by hybridization with 18S rDNA, two submetacentric pairs carrying 5S rDNA sites, and presence of B chromosomes. The B chromosomes of the two species are small, metacentric, and almost totally heterochromatic, with variation of number intra and interindividual. In addition, for the first time in fish, the telomeric sequence [TTAGGG]n was dispersed along the B chromosomes (both species). The [GATA]n microsatellite were scattered in all chromosomes of the A complement and absent in the B chromosomes, in both species. These aspects confirm the phylogenetic proximity between the genus Parauchenipterus and Trachelyopterus, and they suggest the hypothesis that the B chromosomes of the two species might have common origin, previous to the diversification of these genera.

Mutational analysis of the / 亚洲男科学杂志(英文版)

As a crucial transcription factor for spermatogenesis, GATA-binding protein 4 (GATA4) plays important roles in the functioning of Sertoli and Leydig cells. Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility. However, whether GATA4 is associated with human azoospermia has not been reported. Herein, we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia (NOA). We identified a missense mutation (c.191G>A, p.G64E), nine single-nucleotide polymorphisms (SNPs), and one rare variant (c.