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.

HDR syndrome in a Colombian woman with a genital tract malformation: first case report in Latin America / Síndrome HDR en una mujer colombiana con una malformación genitourinaria: primer reporte de caso en Latinoamérica

ABSTRACT Objectives Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is an autosomal dominant transmission hereditary disease with a wide range of penetrance and expressivity. Haploinsufficiency of the GATA3 two finger zinc transcription factor is believed to be its cause. This is the first time this orphan disease is reported in Latin America, so the publishing of this report is expected to raise awareness on these types of syndrome, that are usually underdiagnosed in our region, which in turn causes an increase in the years lost to disability (YLDs) rates, as well as higher costs to be assumed by public health systems. Methods A 36-year-old Colombian woman diagnosed with parathyroid gland agenesis was referred from the Endocrinology Service to the Outpatient Service. According to her medical record, in the past she had developed hypocalcaemia, left renal agenesis, hypoparathyroidism, bicornate uterus and sensorineural hearing loss. Through a genetic analysis a pathological mutation on the short arm of the GATA 3 gen (c.404dupC, p Ala136 GlyfsTER 167) was confirmed, which led to a HDR syndrome diagnosis. Discussion This case proves that there is a possibility that mutations described in other continents may be developed by individuals from our region. Regardless of ethnicity, Barakat syndrome should be considered as a possible diagnosis in patients presenting the typical triad that has been described for this condition, since there could be underdiagnosis of this disease in Latin-America due to the lack of knowledge on this condition in said region, and that genetic counseling in these patients is of great importance for the implications of the syndrome in future generations.(AU)

RESUMEN Objetivos El síndrome de hipoparatiroidismo, sordera neurosensorial y displasia renal (HDR) también llamado síndrome de Barakat, es una enfermedad hereditaria de transmisión autosómica dominante con amplia penetrancia y expresividad genética. El síndrome es causado por la haploinsuficiencia del factor de transcripción de dedos de Zinc GATA3. Esta es la primera vez que esta enfermedad huérfana es reportada en latinoamerica, y buscamos generar consciencia de la presencia de estas enfermedades, las cuales usualmente son infradiagnósticadas en nuestro medio y llevan a un aumento de años perdidos por discapacidad y costos para el sistema de salud pública. Métodos Una mujer colombiana de 36 años ingresó a consulta externa de genética referida por el servicio de endocrinología por una agenesia de paratiroides. La paciente tenía antecedentes de hipocalcemia, agenesia renal izquierda, hipoparatiroidismo, sordera neurosensorial y útero bicorneo. Se realizó un análisis genético que confirmo una mutación patológica en el brazo corto del gen GATA3 (c.404dupC, p Ala136 GlyfsTER 167) diagnóstica del síndrome de Barakat. Discusión Este caso demuestra la posibilidad de existencia de mutaciones descritas en otros continentes en nuestra población. Sin importar la etnia, el síndrome de Barakat debe ser estudiado en pacientes que presenten la triada típica, ya que podría existir un infra diagnóstico de la enfermedad secundario al desconocimiento de la misma en Latinoamérica y teniendo en cuenta la importancia que tiene la consejería genética en estos pacientes por las implicaciones de la enfermedad en futuras generaciones.(AU)

Application of immunohistochemistry for p16 and GATA3 and molecular HPV typing in diagnosis of secondary bladder involvement by cervical carcinoma / 中华病理学杂志

Objective@#To investigate the expression of p16 and GATA3 and the detection of human papillomavirus (HPV) in secondary bladder involvement by cervical carcinomas.@*Methods@#Sixteen cases of cervical carcinoma with bladder involvement diagnosed from December 2008 to March 2016 were collected and evaluated by light microscopy, immunohistochemistry for p16 and GATA3 detection and PCR-reverse dot blot for molecular typing of HPV.@*Results@#The age of the patients ranged from 25 to 76 years with median of 52 years. Morphologically, 14 cases(14/16) showed tumor nests infiltrating lamina propria or muscle bundles of the bladder. By immunohistochemistry, 15 cases (15/16) were found to be diffusely and strongly positive for p16, and 1 showed patchy staining pattern. Seven cases (7/7) of corresponding original cervical cancers were also diffusely and strongly positive for p16. GATA3 staining was negative in 13 cases (13/16), and focal weak to moderate positivity was detected in 3 cases.Three cases (3/7) of corresponding original cervical cancers showed focal weak to moderate positivity of GATA3. Fifteen cases (15/16) showed concordant high risk HPV-positivity, including HPV16 in 8 cases and HPV31 in one case. Five cases showed co-infection of HPV16 and HPV18. One case showed co-infection with HPV18 and HPV45.@*Conclusion@#Differential diagnosis by p16 or GATA3 alone is of limited value. Combination of immunohistochemistry for p16 and GATA3 and molecular typing for HPV detection are useful to distinguish primary bladder carcinoma from the secondary involvement by cervical carcinoma.

Changes in help T cell 1/2 cytokines and transcription factors in cytomegalovirus infected newborn mice and effectiveness of intervention with thymopentin / 中华围产医学杂志

Objective To observe the changes in help T cell 1/2 cytokines and transcription factors in murine cytomegalovirus (MCMV) infected newborn mice and to determine the effectiveness of intervention with thymopentin.Methods One hundred and twenty newborn BALB/c mice were randomized into a blank group,model group and thymopentin group,with 40 mice in each group.Mice in the model and thymopentin group received an intraperitoneal injection of MCMV suspension within 4-6 hours after birth at the dosage of 20 μ L to and tissue culture infections dose of 10431 U/0.1 ml,establish a systemic infection model,and the same volume of normal saline was injected into mice in the control group.Mice in the thymopentin group also received thymopentin 0.3 mg/(kg · d).On Day 3,5,7,10 and 14,8 mice in each group were sacrificed and their splenic tissues were harvested.Interferon (IFN) γ and interleukin (IL)-10 expression in the supernatant of a splenic lymphocyte culture was assessed by enzyme-linked immunosorbent assay.T-bet/GATA-3 mRNA in splenic tissues were analyzed using reverse transcription-polymerase chain reaction.One way ANOVA,including LSD and Dunnett T3 methods,was used for statistical analysis.Results (1) IFN-γ expression in the model and thymopentin groups peaked on Day 3,and was higher than that in the control group [(280.73 ± 14.88),(286.03 ± 15.44) and (149.42±5.43) pg/ml,respectively,F=183.532,P=0.000].Expression in the thymopentin group decreased after Day 3,and increased by Day 7.At Day 14,the IFN-γ expression level in the thymopentin group was higher than that in the control and model groups [(252.33±8.33),(149.07±7.05) and (148.57±4.53) pg/ml,respectively,F=385.487,P=0.000].(2) IL-10 expression in the model group gradually increased.By Day 14,the expression became obviously higher than that in the control and thymopentin groups [(71.19± 1.50),(36.67 ± 2.55) and (40.01 ± 1.28) pg/ml,respectively,F=523.670,P=0.000].IL-10 expression in the thymopentin group increased after Day 3 and decreased by Day 7.On Day 14,the expression in the thymopentin group was lower than that in the model group,but higher than that in the control group.(3) T-bet mRNA expression was obviously increased in the model and thymopentin groups.On Day 3,the expression was higher than that in the control group (relative value of gray-scale:0.74±0.02,0.71 ±0.04 and 0.30±0.01,respectively,F=741.630,P=0.000).By Day 3,the expression in the thymopentin group decreased,and gradually recovered on Day 5,and on Day 14 it was higher than that in the control and model groups (relative value of gray-scale:0.45 ± 0.01,0.30±0.01 and 0.30±0.01,respectively,F=257.571,P=0.000).(4) GATA-3 mRNA expression in the model and thymopentin groups increased on Day 3,and was higher than that in the control group (relative value of gray scale:0.48±0.02,0.53±0.01 and 0.33±0.01,respectively,F=345.167,P=0.000).On Day 14,the expression in the model group was higher than that in the thymopentin group,which was higher than that in the control group (relative value of gray-scale:0.99 ± 0.02,0.55 ± 0.02 and 0.34 ± 0.01,respectively,F=1 767.505,P=0.000).Conclusions A Th1/Th2 shift may be induced in MCMV infected neonatal mice,which manifests as a state of predominant Th2 response.Thymopentin can ameliorate this situation.

The Influence of CagA on the Differentiation of Helper T Lymphocytes in Chronic Gastritis / 天津医药

Objective To evaluate the influence of cytotoxin-associated gene A (CagA)to the differentiation of helper T lymphocytes in chronic gastritis. Methods Eighty patients with chronic gastritis were included in this study. The serum antibody against CagA was detected by the enzyme-linked immunosorbant assay (ELISA). Patients were divided into CagA-positive group and CagA-negative group according to the results of ELISA. Pathologic changes in gastric mucus were respectively analyzed. In addition, the expressions of nuclear transcription factors in gastric mucus including TBX 21, GATA-3, FoxP3 and Rorγt were detected by PCR and Western blot assay. Results There were 52 patients in CagA-positive group and 28 patients in CagA-negative group. The gastric inflammation was more serious in CagA-positive group than that in CagA-snegative group. There was no significant difference in Hp density between two groups. The expressions of GATA-3 and FoxP3 were much higher, while the transcription and protein expression levels of TBX21 and Rorγt were significantly lower in CagA-positive group than those in CagA-negative group. Conclusion Although the inflammation in gastric mucus was more serious in CagA-positive patients, Hp can not be effectively eliminated,which may relate to the differentiation of Th0 into Th2/Treg cells.

Relationship between GATA-3 and T-bet and inhibition of differentiation of human T helper cells by morphine / 中华麻醉学杂志

Objective To evaluate the relationship between GATA-3 and T-bet and inhibition of the differentiation of human T helper cells by morphine.Methods Ten healthy volunteers,aged 20-50 yr,weighing 50-70 kg,were enrolled in the study.Peripheral venous blood samples were taken in the early morning.Peripheral blood mononuclear cells (PBMCs) were isolated and assigned into 5 groups (n=10 each).PBMCs were incubated routinely (group C).PBMCs were incubated in the presence of PMA and ionomycin (group P),morphine 50 μg/ml (group M),morphine 50 μg/ml + naloxone 50 μg/ml (group MN) or naloxone 50μg/ml (group N),and were then stimulated with PMA and ionomycin for another 4 h.The percentage of Th1 and Th2 cells was detected by flow cytometry.The Th1/Th2 ratio was calculated.Interferon (IFN)-γ and interleukin (IL)-4 concentrations in the supematant were determined using ELISA.The activities of GATA-3 and T-bet were analyzed by EMSA.Results Compared with group P,the percentage of Th1 and Th2 cells,Th1/Th2 ratio,IFN-γand IL-4 concentrations in the supernatant,and GATA-3 and T-bet activities were significantly decreased in group M,the percentage of Th1 cells,Th1/Th2 ratio,and IFN-γ concentration in the supernatant were significantly decreased in group MN (P ＜ 0.05 or 0.01).Compared with group M,the percentage of Th1 and Th2 cells,Th1/Th2 ratio,IFN-γ and IL-4 concentrations in the supernatant,and GATA-3 and T-bet activities were significantly increased in group MN (P ＜ 0.05 or 0.01).There was no significant difference in the indexes mentioned above between groups N and C (P ＞ 0.05).Conclusion Morphine inhibits the differentiation of human T helper cells by activating opioid receptors,which may be related to the inhibition of GATA-3 and T-bet activities.

Mechanism of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 mediated anti-neoplastic effects of cytokine-induced killer cells / 白血病·淋巴瘤

Objective To investigate the molecular mechanism underlying lymphocyte functionassociated antigen-1 (LFA-1) / intercellular adhesion molecule-1 (ICAM-1) mediated anti-neoplastic effects of cytokine induced killer (CIK) cells. Methods Lymphocytes isolated from peripheral blood of children leukemia were induced with interferon-gamma (IFN-y), anti-CD3 monoclonal antibody (CD3McAb) and interleukin-2 (IL-2) and co-cultured with dendrite cells (DC) to generate DC-CIK cells. When treated with LFA-1 monoclonal antibody, cytotoxicity of DC-CIK cells against leukemia cell lines was measured by the MTT assay, while RT-PCR and Western blotting were used to determine mRNA and protein expressions of GATA-3 and T-bet in DC-CIK cells, respectively. IL-12, IFN-γ and tumor necrosis factor-α (TNF-α) levels released by DC-CIK cells were quantified by ELISA. Results Induced DC-CIK cells were regular, round and transparent with variable cell volume and cellular aggregation. When treated with mouse anti-human LFA-1 monoclonal antibody, the cytotoxicity decreased mostly towards B95 cells under administration of 20 μg/ml LFA-1 monoclonal antibody in comparison with the control group(t =10.138, P ＜0.05). It led to a highest elevation of GATA-3 mRNA and protein levels (t =16.386, P ＜ 0.05; t =22.652, P ＜ 0.05) and a most decrease of T-bet mRNA and protein levels (t =17.728, P ＜0.05; t =17.452, P ＜0.05) under 20 μg/ml LFA-1 monoclonal antibody in B95 cells group in comparison with the control group. The expression levels of IL-12,IFN-γ, and TNF-o in supernatant were the lowest under 20 μg/ml LFA-1 monoclonal antibody in B95 cells group in comparison with the control group (t =21.621, P ＜0.05; t =13.739, P ＜0.05; t =15.278, P ＜0.05).Conclusion GATA-3 and T-bet were implicated in the LFA-1/ICAM-1 mediated anti-neoplastic effects of DC-CIK cells via activation of the Th1 pathway, with high secretion of Th1 cytokines, such as IL-12, IFN-γ and TNF-α.

The study on the role of transcription factor GATA binding protein 3 in familial Alzheimer's disease pathogenesis / 中华神经科杂志

Objective To investigate the mechanisms of decreasing insulin degrading enzyme (IDE) level by mutation V97L in the gene presenilin 1 (PS-1).Methods Transcription factor GATA binding protein 3 (GATA-3) activity was assessed by protein/DNA array and verified by Western blot in SH-SY5Y cells transfected by PS-1 mutation V97L.Results Protein/DNA array and Western blot revealed that there was increased transcript factor activity (5.5 times high) and protein level of GATA-3 in V97L-PS-1 transfected SH-SY5Y cells.Transcription factor GATA-3 can bind to the IDE promoter and negatively control the IDE transcription level.Conclusion PS-1 mutation V97L may regulate the transcription of IDE via GATA-3, and subsequently involve in deposition of Aβ42 and development of Alzheimer's disease.

Relationship of GATA3 with development and progression of breast cancer / 第二军医大学学报

GATA3 transcription factor plays an important role in the growth and differentiation of normal breast tissues, and it is also closely related to the tumorigenesis of breast cancer. The roles of GATA3 vary in different breast cancer subtypes. This paper reviews the relationship of GATA3 with normal breast tissue and the tumorigenesis of breast cancer, in an attempt to provide theoretical evidences for future clinical applications of GATA3 in breast cancer.

Transcription factor GATA-3 on rats Th2 type cytokine expression regulation after infected by respiratory syncytial virush / 中国医师杂志

Objective To study the expression regulation of GATA-3 on Th2 cytokines secretions in rats lung infected by respiratory syncytial virus (RSV).Methods 20 SD rates were random divided into two groups: Control group (10 rats) and RSV-infected group(10 rats, the model was established by RSV intravasation).The airway responses were observed after seven week.Lung tissue of SD rats were stained with HE, pathologic examinations of lung tissue- stained were made.GATA-3 expressions in lung tissue were detected by western-blots, respectively.Interleukin-4 (IL-4) and interleukin-5 (IL-5) in lung homogenate were detected by ELISA.Results Lung biopsy from RSV-infected group showed typical inflammation under light microscope.Airway resistance in RSV- infected group was higher than control group.Compared with control group( 1.231 ±0.31 ), the expression of GATA-3 significantly increased in RSV-infected group (1.743 ±0.21)( t =15.427, P ＜0.01).The levels of IL-4[(142.3 ± 12.3)ng/L] and IL-5[(167.5 ±14.2) ng/L] increased in RSV-infected group [(69.2±11.6) ng/L, ( 86.6 ± 14.3 ) ng/L] ( P＜0.01 ).There was a positive correlation between protein levels of GATA-3 and IL-4 in lung tissues (r=0.864, P＜0.01 ), and a positive correlation between GATA-3 and IL-5 in lung tissues(r=-0.756, P＜0.01).Conclusion RSV-infection may up regulate the expression of GATA-3 in lung, which contributed to inflammation of Th2 type.