ABSTRACT
ABSTRACT This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.
RESUMO Neste artigo, objetivamos apresentar os achados da tomografia de coerência óptica em uma nova mutação detectada no gene NEU1 em um caso de síndrome macular vermelho-cereja bilateral associada à sialidose tipo 1. Um paciente de 19 anos com um achado de mancha macular vermelho-cereja foi submetido a análises metabólicas e genéticas, apoiadas por imagens de tomografia de coerência óptica de domínio espectral (SD-OCT). Ao exame de fundo de olho, foi observada uma mancha macular vermelho-cereja bilateral. Nas imagens de SD-OCT, observou-se hiper-refletividade nas camadas internas da retina e na camada fotorreceptora na região foveal. Foi realizada uma análise genética e uma nova mutação foi detectada no gene NEU1, resultando em sialidose tipo 1. Nos casos em que é detectada uma mancha vermelho-cereja na mácula, o diagnóstico diferencial de sialidose deve ser feito e mutações do gene NEU1 devem ser rastreadas. A SD-OCT por si só não é suficiente para o diagnóstico diferencial, porque achados de aparência semelhante podem se manifestar em casos de doenças metabólicas da infância.
ABSTRACT
Resumen El síndrome de Hamman, o neumomediastino es pontáneo, es la presencia de aire en mediastino en pacientes sin antecedentes de enfermedad pulmonar previa, trauma torácico o iatrogenia. Se ha descrito como una complicación rara en pacientes con neumo nía por COVID-19. Se postula que un aumento en la presión de la vía aérea asociado a daño alveolar difuso generado por el virus, producen una fuga de aire hacia el mediastino. El dolor torácico y disnea, asociado a enfisema subcutáneo, deben hacer sospechar al médico tratante. Presentamos un paciente de 79 años que du rante su internación por neumonía secundaria al virus SARS-CoV-2 evolucionó súbitamente con disnea, dolor torácico, accesos de tos y broncoespasmo con hallaz go de neumomediastino espontáneo en la tomografía de tórax. Evolucionó favorablemente con tratamiento broncodilatador y oxigenoterapia. El síndrome de Ham man es una causa poco frecuente de progresión de insuficiencia respiratoria en pacientes con neumonía por COVID-19. Su identificación es crucial para imple mentar el tratamiento adecuado.
Abstract Hamman's syndrome, or spontaneous pneumome diastinum, is the presence of air in the mediastinum without a history of previous pulmonary pathology, chest trauma or iatrogenesis. It has been described as a rare complication in patients with COVID-19 pneu monia. It is postulated that an increase in airway pres sure associated with diffuse alveolar damage caused by the virus produces an air leak into the mediastinum. Chest pain and dyspnea associated with subcutaneous emphysema should make the treating physician suspi cious. We introduce a 79-year-old patient who, during hospitalization for pneumonia secondary to COVID-19, suddenly developed dyspnea, chest pain, coughing spells and bronchospasm with the discovery of spontaneous pneumomediastinum on chest tomography. He evolved favorably with bronchodilator treatment and temporary oxygen therapy. Hamman's syndrome is a rare cause of respiratory failure progression in patients with COVID-19 pneumonia. Its recognition is crucial to implement the appropriate treatment.
ABSTRACT
Resumen Introducción: La descompresión microvascular (DMV) en la neuralgia trigeminal es una técnica quirúrgica cuyo objetivo es revertir la compresión a la que se ve someti do un nervio por una estructura vascular. El objetivo de este estudio fue realizar una comparación directa entre la descompresión microvascular endoscópica (DMV-E) y la misma a través del uso del microscopio (DMV-M) en el tratamiento de la neuralgia del trigémino. Métodos: Se realizó un estudio de cohorte retrospec tivo de pacientes operados de neuralgia de trigémino, por un mismo cirujano, entre 2015 y 2021 en nuestra institución, tanto por técnica microquirúrgica como endoscópica. Resultados: Se obtuvieron un total de 31 pacientes divididos en dos grupos: Grupo M correspondiente a 15 (49%) pacientes abordados con técnica microscópica y Grupo E, con 16 (51%) pacientes intervenidos con técnica endoscópica. Se identificaron diferencias en el tamaño de la cra niectomía, más pequeña en el grupo E (2.50 cm vs 3.70 cm grupo M); y en el tiempo de internación, de 2.43 días en el grupo E vs. 4.46 días en el grupo M. El tiempo de cirugía fue similar para ambas técnicas quirúrgicas La principal compresión fue dada por la arteria ce rebelosa superior (ACS) en ambos grupos. Todos los pacientes presentaron mejoría del Barrow Neurological Institute Pain Intensity Score (BNI) en el postoperatorio en ambos grupos. Discusión: La DMV-E constituye una alternativa qui rúrgica interesante a la ya conocida DMV-M para el tratamiento de la neuralgia trigeminal, por requerir menores dimensiones en la incisión cutánea y tamaño de la craniectomía, acortando el tiempo de internación, lo cual no solo implica un beneficio para el paciente, sino que también representa menor costo de internación.
Abstract Introduction: Trigeminal neuralgia is a highly invali dating pathology, whose natural course has been modi fied thanks to decompressive microvascular surgery. The intervention can be carried out either with a microscope or via an endoscopic technique. Our goal was to compare these two techniques for the treatment of this complex pathology. Methods: Retrospective, analytical study of a cohort of patients treated by a single surgeon at our institution, in the period between 2015 and 2021. Results: We identified 31 patients and divided them into two groups: 15 (49%) treated using the microscopic technique (group M), and 16 (51%) exclusively via an endoscopic one (group E). Differences were observed between the means of the size of the craniectomy in group M (3.7 cm) compared to group E (2.5 cm); The mean length of hospital stay for patients in group E was shorter (4.46 days compared to that of patients in group M, whose hospital stay averaged 2.43 days). There were no differences between the two groups regarding the length of the procedure. In both groups, the predomi nant compression was due to the superior cerebellar artery (SCA). Pain outcomes were equivalent, with every patient in both groups having an improved postoperative Barrow Neurological Institute Pain Intensity Score (BNI). Discussion: Endoscopic microvascular decompression is an attractive option for the resolution of neurovas cular conflict as it provides functional results similar to the microscope technique, without requiring an exten sive craniectomy and associated to shorter in-hospital stay, which is beneficial for both the patient and the institution.
ABSTRACT
Epidermal growth factor receptor 2 (HER2) is an oncogene involved in tumour genesis and progression. It is expressed in 7% of patients with colorectal cancer (CRC) and is associated with drug resistance of epidermal growth factor receptor monoclonal antibodies. With the emergence of the therapeutic dilemma of CRC and the survival benefits of targeting HER2 for patients with breast cancer and gastric cancer, the significance of HER2 in CRC and the prognostic value of anti-HER2 therapy have been widely concerned, clinical researches on HER2-positive CRC have been continuously carried out. Currently, the diagnostic criteria for HER2 positive CRC have gradually been unified. HER2-targeting therapies such as monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug coupling and HER2-related immunotherapy alone or in combination have shown good efficacy and brought significant survival benefits for HER2 positive CRC. This paper reviews the research progress of HER2 in CRC.
ABSTRACT
Sialidosis is a rare lysosomal storage disease caused by NEU1 gene mutation at 6p21.33. It is characterized by myoclonic, ataxia, epilepsy, and decreased vision. A pair of twins with sialidosis type 1 are reported to enrich clinicians ′ understanding of the disease, so as to improve the diagnosis and treatment. The proband was a 16-year-old male. The main symptom was intermittent limb involuntary trembling for 2 years, with paroxysmal loss of consciousness. Fundus examination showed cherry-red spots. His twin brother had similar symptoms, but the overall performance was mild. Whole exome sequencing results showed that both patients carried compound heterozygous mutations of c.239C>T (p.P80L) and c.803A>G (p.Y268C) in NEU1 gene, which were from their normal phenotype mother and father.
ABSTRACT
Neural recording electrodes enable the acquisition and collection of electrical signals from neu-rons,and these recorded neural electrical signals are an important means of understanding neuronal activity.As a major component of the brain-machine interface,neu-ral recording electrodes serve as a bridge between the nervous system and external devices.The extracted information can be used to understand the state of the brain and acts as a feedback signal to regulate external devices,thus providing important information for the clini-cal treatment of neurological diseases.Moreover,the electrodes can be used as a vehicle for drug injection to directly treat diseases.Since the time that Strumwas-ser used microwires to achieve long-term recordings of neural activity in hibernating squirrels,implantable elec-trode technology has gradually improved over three gen-erations of development,and progress has been made in improving the biocompatibility,mechanical performance(size,shape,density,etc.),and signal-to-noise ratio.Implantable neural recording electrodes can acquire sig-nals from cortical and deep neural clusters,with the advantages of high signal-to-noise ratio,information con-tent,and spatial/temporal resolution.However,there is still a need to improve the structure and performance of these electrodes;for example,their high invasiveness and lack of biocompatibility pose technical difficulties in the process of translation to the clinic.This paper reviews the basic requirements for electrodes,main recording methods and signal types,common types of implant-able neural recording electrodes,and their challenges and future development directions.With the continuous development of electrode materials,equipment,systems,and neurotechnology,it should be possible to apply neu-ral recording electrodes in clinical practice,to promote safe and efficient treatment of human diseases.
ABSTRACT
OBJECTIVE There are serious hazards in depression,and the precise mechanism underlying the delayed onset of clinical antidepressants remains unclear.The purpose of this study was to investigate the regular pattern of the speed-limiting role of excitation/inhibition(E/I)function balance in the mechanism of antidepressant action.METHODS Based on the previous study,we focused on glutamatergic pyramidal neurons in the medial prefrontal cortex(mPFC)here and used its excitability to represent the establishment of a new E/I functional balance.We studied the changes in the firing activity of glutamatergic pyramidal neuron in the mPFC at different administration times for five types of antidepressants that act on different pharmacological targets and different onset times,including fluoxetine(SSRI),duloxetine(SNRI),vilazodone[serotonin 1A receptor(5-HT1A)ago-nist and SSRI],ketamine[N-methyl-D-aspartate(NMDA)receptor antagonist],and hypidone hydrochloride(YL-0919,new antidepressant with sigma-1 receptor ago-nist and SSRI).We first examined the initial onset time of activation of pyramidal neurons using multichannel elec-trophysiological recordings and tested the antidepressant behavioral effects using the FST.We then selected three antidepressants(fluoxetine,ketamine,and vilazodone)to explore its effects on the BDNF-mTOR pathway by West-ern blotting.In addition,we disrupted the E/I function bal-ance using chemogenetics to investigate the antidepres-sant-like effects of YL-0919 and ketamine in the FST and TST.RESULTS We found that treatment with fluoxetine for 17 days significantly increased the firing activity of pyramidal neurons and decreased the immobility duration in the FST.Similarly,it took duloxetine for 10 d,vilazodone for 4 d,YL-0919 for 3 d and ketamine for 24 h,to exert such effects.Meanwhile,Western blotting results sug-gested that the expression of BDNF and phosphorylation of mTOR in the mPFC significantly increased.How-ever,haloperidol,a classic antipsychotic(without antide-pressant effects),exerted no such effects on the firing activities of pyramidal neurons.In addition,disrupting the E/I function balance(via activating the GABA neurons and inhibiting the glutamate neurons)blocks out the antidepressant-like effects of YL-0919 and ketamine in the FST and TST.CONCLUSION Taken together,our findings suggest that the commencement of antide-pressant effects may be accompanied by the increase in the firing activity of pyramidal neurons and the activation of the BDNF-mTOR pathway,which may be a necessary and rate-limiting process.The re-establishment of the E/I balance may be a landmark event for the onset of antide-pressant effects.
ABSTRACT
Purpose: The present study aims to identify basaloid and luminal molecular groups and the p53-like sub-group, which is a sub-group of the luminal group, using a specific immunohistochemical panel and investigate human epithelial growth factor receptor 2 (HER2)/Neu and Fascin expression in these groups to analyze their relationship with clinicopathological features and prognosis in a cohort of cases with muscle-invasive urothelial bladder carcinoma (MIBC). Material and Methods: An immunohistochemical panel that included GATA-3, CK20, CD44, and CK5/6 was used to identify molecular sub-groups based on expression in 44 cases of MIBC. HER2/Neu and Fascin expression in basal, luminal, and p53-like groups and the relationship with clinicopathological features and prognosis were investigated. Results: The distribution of the molecular sub-groups determined by immunohistochemistry was as follows: 23 luminal cases (52.3%), 16 basal cases (36.4%), and 5 (11.4%) p53-like cases. There was a statistically significant difference in tumor size across the groups, with the greatest size in the p53-like group (p = 0.001). A statistically significant difference was observed in HER2/Neu expression between the molecular sub-groups (p = 0.017). Comparison of survival and HER2/Neu scores revealed shorter survival in patients with an HER2/Neu score of 3 + compared to those with scores of 0, 1+, and 2+ (p = 0.109). Fascin immunoreactivity was more common in the p53-like and basal groups compared to the luminal group (p = 0.036). Conclusion: Despite the limited number of cases in the MIBC group, our results support that HER2/Neu expression in the luminal sub-group and Fascin expression in basal and p53-like groups may be used as a negative prognostic marker. Multi-center studies that include large case series are warranted in this field.
ABSTRACT
Aim: To assess HER2/neu expressions and correlate with E-cadherin and Serum HER2 level in gastric carcinoma. Method: 31 gastric biopsies and 1 resected specimen were taken in the study with patient details and stained with H and E for histopathological details following Lauren's classification. Immunohistochemistry for HER2 and E-cadherin expression was conducted followed by serum HER2/neu ELISA. Result: Adenocarcinoma with 61% diffuse, 29% intestinal, and 10% other type were observed with predominant HER2 immunoexpression in intestinal-type than in diffuse-type adenocarcinoma. Other observations marked 44% as 3+/positive and 56% as 2+/equivocal in intestinal type while 26% cases as 3+/positive, 69% as 2+/equivocal, and 1% as 1+/negative were observed in diffuse type. The data presented 33% membranous positivity and 67% both membranous + cytoplasmic positivity in intestinal type while 2% showed membranous positivity, 47% both membranous + cytoplasmic, and 42% only cytoplasmic positivity in diffused type. On comparing the localization pattern of HER2 and E-cadherin, 25% of cases showed membranous staining while 50% of cases showed membranous with cytoplasmic staining for both. No cytoplasmic HER2 staining as well as no any staining for E-cadherin was shown by 6% cases. Conclusion: Thus, it can be concluded that cytoplasmic expression of HER2 in gastric adenocarcinoma (mainly diffuse type) may be due to shedding of its extracellular domain, leading to loss of membranous E-cadherin expression on immunohistochemistry. The loss of membranous expression of E-cadherin and increased serum HER2 ELISA were correlated well with these findings.
ABSTRACT
Background: Gastric carcinoma is a major cause of cancer-related morbidity and mortality worldwide. Gastric neoplasms arise from genetic and epigenetic changes in various genes. Present study evaluates the immunoexpression of PTEN, HER2/neu, and Ki-67 in endoscopic gastric carcinoma biopsies and correlates the expression of these proteins with clinicopathological features. Material and Methods: Adequate endoscopic biopsies of 27 cases of gastric carcinoma were evaluated for World Health Organization (WHO) and Lauren's classification subtypes along with HER2/neu, PTEN, and Ki-67 immunoexpression. HER2/neu immunostaining was scored as proposed in the Trastuzumab for gastric cancer (ToGA) trial while PTEN staining and downregulation were assessed using an immunoreactive score. The cut-off for Ki-67 expression was taken as 90th percentile of the values in adjacent non-neoplastic tissue. All statistical analysis was done at 5% level of significance with SPSS v22 statistical software. Results: Tubular adenocarcinoma was the commonest WHO histological subtype and 56% of cases were of intestinal type as per Lauren's classification. 55.6% of cases showed a complete loss of PTEN expression in neoplastic tissue. 17 of the 19 cases with adjacent non-neoplastic tissue showed PTEN downregulation in neoplastic tissue. 81.5% of cases had a high Ki-67 index and HER2/neu overexpression was noted in 36% of cases. All the four cases who died had high Ki-67 proliferation indices; 3 patients had loss of PTEN expression and HER2/neu overexpression. Conclusion: We conclude that these immunomarkers can play important role in the behavior of gastric carcinomas and can be targeted for new therapies.
ABSTRACT
Background: Ovarian cancer is one of the most common malignancies in female patients. In recent years, immunohistochemistry (IHC) has emerged as an important tool in the diagnosis of ovarian tumors. The study aimed to assess estrogen receptors (ERs), progesterone receptors (PRs), Her-2-neu, and Ki-67 by IHC in surface epithelial ovarian tumors and to correlate the findings with different variables. Materials and Methods: It was a cross-sectional study. Oophorectomy/salpingo-oophorectomy/cystectomy specimens were included in this study. IHC was done on 10% neutral buffer formalin-fixed paraffin-embedded tissue sections by using Dako FLEX Ready to use mouse monoclonal antibodies and DakoEnvisionTM FLEX/ HRP detection reagent. Results: The study includes 81 cases of surface epithelial ovarian tumors (a benign serous tumor [20], a benign mucinous tumor [18], a borderline mucinous tumor [5], low-grade serous carcinoma [8], high-grade serous carcinoma [19], mucinous carcinoma [7], endometrioid carcinoma [2], borderline Brenner tumor [1], and malignant Brenner tumor [1]. ER had higher expression in malignant cases (51.33%) than in benign cases (15.8%). PR had higher expression in malignant tumors (54.05%) incomparable to benign (18.42%) and borderline tumors (16.66%). PR had higher expression in high grade. Expression of Her-2-neu positivity was found to be 29.7% out of the total 81 cases. Her-2-neu was found in 11 high-grade tumors among 31 malignant cases. CA-125 levels were significantly higher in malignant ovarian tumors (P = 0.0143). Proliferation activity was considered low if proliferation index (PI) <10% and high if PI >10%. The study showed high PI in malignant tumors. Conclusion: Expression of these marks in adjunct to H&E diagnosis may prove beneficial in differentiating benign, borderline, and malignant cases, in which a diagnosis of borderline cases based on sole H & E is doubtful.
ABSTRACT
RESUMEN Introducción: El carcinoma mamario negativo a la expresión de receptores hormonales (RH negativo) incluye los subtipos moleculares Her-2/neu y triple negativo, asociados ambos a una mayor actividad biológica del tumor y un pronóstico desfavorable. Objetivo: Determinar la incidenciade los carcinomas triples negativos y Her-2/neu en carcinomas mamarios y su relación con variables clínico-patológicas de valor pronóstico. Métodos: Se realizó unestudio descriptivo, de corte transversal, en el Hospital Celestino Hernández, Villa Clara, entre enero de 2017 a junio de 2019. Se incluyeron 293 mujeres con diagnóstico de carcinoma de mama infiltrante, a cuyas biopsias se les realizó estudio inmunohistoquímico determinando la incidencia de los subtipos moleculares triple negativo y Her2/neu y su relación con otras variables de valor pronóstico. Resultados: En la serie se determinó la incidencia de los subtipos moleculares triples negativo y Her2/neu. En ambos subtipos moleculares, más de las dos terceras partes de las pacientes fueron mayores de 50 años, presentaron tallas tumorales mayor de 2 cm en el momento del diagnóstico y tuvieron histología ductal. Destaca además la relación de ambos subtipos moleculares con formas histológicas moderada y pobremente diferenciadas del carcinoma mamario. De igual forma, en ambos subtipos, el índice de proliferación determinado por Ki67 fue alto en más de las dos terceras partes de las pacientes estudiadas. Conclusiones: La edad posmenopáusica, el tipo histológico ductal, el grado histológico alto, el alto índice de Ki67 y la talla tumoral mayor de 2 cm se asocian con frecuencia a subtipos moleculares del carcinoma mamario negativos a receptores hormonales.
ABSTRACT Introduction: The breast carcinoma which is negative to the expression of hormonal receptors (negative RH) includes the molecular subtypes Her2/neu and triple negative, that are both associated to higher biological activity and a worse forecast. Objective: To determine the real incidence of the subtypes triple negative and Her2/neu in breast carcinoma and its correlation with prognostic value clinic-pathological variables. Methods: A descriptive, cross-sectional study was done in the Hospital Celestino Hernández, Villa Clara, from January 2017 to June 2019. It was included 293 women with diagnosis of infiltrating breast carcinoma, whose biopsies were studied by immunohistochemistry, determining the incidence of the molecular subtypes triple negative and overexpression of Her-2 and its correlation with others prognostic value variables. Results: In the series it was determined the incidence of the molecular subtypes triple negative and Her2/neu. In both molecular subtypes more two third of patients were older than 50 years old, had tumor size larger than 2 cm at the moment of diagnosis and had ductal histology. The correlation of the both molecular subtypes with moderately and poorly histological types of breast carcinoma stands out. In the same way the proliferation index determined by Ki67 was high in more two third of the studied patients. Conclusions: The post-menopausal age, the ductal histologic type, high histologic grade, high index of Ki67 and tumor size larger than 2 cm are often associated to molecular subtypes of breast carcinomas which are negative to the expression of hormonal receptors.
ABSTRACT
Background: Malignancy of breast is the leading cause of cancer deaths in women. Molecular organisation of breast cancer is considered as better predictive factor for diagnosis and treatment. The present study was done with the aim to find out clinicopathological characterization and correlation of breast tumor with receptor status progesterone (PR), estrogen (ER) and human epidermal receptor protein-2/neu status (HER-2/neu).Methods: This was a prospective study done on 50 patients with breast carcinoma. The expression patterns of PR, ER and HER-2/NEU were studied. Clinical features, pathologic features such as age of the patient, tumour size, grade, and lymph node status and their correlation with receptors were compared.Results: Of the 50 patients, ER positivity was seen in 42% cases, PR positivity in 32% and HER-2/neu (3+) in 30% cases. Majority of grade I tumors were ER and PR positive and majority of grade III tumors were triple negative. Triple negative profile was seen in secretory carcinoma. ER, PR and HER2 status was not significantly associated with age of the patients and tumour size. The immunohistochemical types ER/PR +ve Her2neu +ve and ER/PR -ve Her2neu -ve are significantly related to grading of tumours.Conclusions: From the results, it was concluded that ER, PR and HER-2 status correlates well with histopathological grading. These results highlight the fact that molecular subtypes correlate with diagnosis and aid in targeted therapy.
ABSTRACT
Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage treatment. We determined frequency of C-MET gene copy number variation (CNV) by Fluorescent in-situ hybridization (FISH) in gastric adenocarcinoma (GAC) and sought its correlation with conventional clinicopathologic parameters. Dual-coloured FISH was done on 32 GAC cases. C-MET gene and centromere 7 signals were counted under fluorescent microscope and ratio was calculated for each case. Correlation between C-MET CNV and conventional clinic-pathologic parameters was done by Fischer exact test. CNV was identified in the form of amplification and polysomy (3.1% each) and associated with poorer prognostic parameters. Our pilot study highlights limited subset of patients that may benefit from anti-C-MET-targeted therapy and thus could be a novel biomarker for targeted intervention in GAC.
ABSTRACT
Human epidermal growth factor receptor HER2/neu status is an important prognostic factor for breast cancer as it is crucial in stimulating growth and cellular motility. Overexpression of HER2/neu is observed in 10%?35% of the human breast cancer and is associated with prognosis and response to treatment. The magnitude of amplification must be determined to facilitate better prognosis and personalized therapy in the affected patient. This study aims to investigate the HER2/neu status in breast cancer by concurrent HER2/neu protein overexpression immunohistochemically with HER2/neu DNA amplification by quantitative real-time polymerase chain reaction (PCR), allowing accurate and precise quantification of HER2/neu amplification after a follow-up period. A total of 54 paired tissue samples from formalin-fixed paraffin-embedded (FFPE) breast cancer patients enrolled in this study were collected to evaluate tumor and normal tissues. Only cases with 80% and more tumor cells were included. For confirmation of immunohistochemistry (IHC) results, qPCR was used to determine the HER2/neu amplification. The association between clinicopathological variables like age, tumor size, histological grade, stage, lymph node status, hormone receptor status, family history, recurrence rate, and vital status was evaluated. We observed that 11/54 (20.4%) of the tumor tissues are positive for HER2/neu protein overexpression by IHC. A total of 8 out of these 11 cases (72.7%), which presented a score of 3+, showed gene amplification of HER2/neu. The concordance rate between IHC and qPCR was 94.4%. HER2/neu gene amplification was found to be significantly associated with recurrence, increased risk of death, and progesterone receptor status, supporting a negative prognostic role of HER2/neu in breast cancer survival. In conclusion, IHC can be used as an initial screening test to detect HER2/neu protein overexpression, and the use of qPCR can verify the IHC results and establish HER2/neu status in routine clinical practice.
ABSTRACT
Aim To study the effect of melatonin receptor agonist Neu-pl 1 on IR in T2DM rats and to predict its possible mechanism. Methods Long-term high-fat feeding plus low-dose streptozotocin (STZ, 30 mg • kg"1, IP) were used to induce an animal model of type 2 diabetes in female rats. After 4 weeks of intragastric administration, liver tissue was sacrificed. Hie mRNA expression levels of Sirtl, Nrf-1/2 and ERRa in rats were determined by RT-PCR. The relative expressions of PGC-la and Mfn2 were determined by Western blot. Rat INS was measured and HOME-IR and ISI were calculated. The liver ATP content and ATPase activity were measured. Results Compared with normal group, T2DM rats developed IR, PGC-la, Mfn2 protein expression increased, Sirtl and other mRNA expression decreased significantly, ERRa mRNA expression increased, ATP content decreased significantly, and ATPase activity decreased. Compared with model group, the Neu-pll low-dose group reduced INS in T2DM rats, improved IR in T2DM rats, up-regulated rat liver protein and mRNA expression, down-regulated ERRa mRNA expression, and increased rat liver ATP content and ATPase activity. Conclusions The melatonin receptor agonist Neu-pl 1 may improve IR by regulating the mitochondrial bal-ance-related factors in liver of T2DM rats and maintaining normal mitochondrial function.
ABSTRACT
Introduction: Neo-adjuvant chemotherapy (NACT) isconsidered as initial management of all patients with locallyadvanced breast cancers and followed by surgery. NACTenables reduction of breast tumor size- thereby prolongingsurvival and altered the expression of steroid receptor (ER/PR)and Her-2/NEU in the cancer cells. Our aims and objectivewas to look into the association of patient age, tumor grade,expression status of ER/ PR / Her-2/neu receptor status beforeand after NACT in Indian women patients.Material and methods: The study was conducted over aperiod of 4 years. Hormone receptor and Her-2/neu status wasdetermined by IHC over 412 samples. The patients receivingNACT and having both core needle biopsy and surgery(MRM) are considered as NACT group. The other group didnot receive NACT but have core needle biopsy and surgeryare taken as non NACT group. The discordance was comparedbetween these two groups.Results: Patients of more than 40years of age hadpredominantly favorable hormone receptor status expression.In the NACT group favorable receptor status was 60.35%and discordance was higher in ER, PR and HER- 2/neu incomparison to non-NACT group.Conclusions: Significant alteration of hormone receptorsand Her-2/neu expression was found in biopsy of the patientsreceiving NACT. So reevaluation of the hormonal status andHer 2 neu receptor in residual invasive carcinoma may beconsidered as it has advantage on chemotherapy after finalsurgery.
ABSTRACT
Background: Carcinoma of the breast is a truly complex disease with a large intratumoral heterogeneity, leading to markedly variable clinical course and response to treatment modalities. Prognosis and management of breast cancer are influenced by variables such as stage, grade, hormone receptor status of estrogen(ER), progesterone(PR) and Human epidermal growth factor receptor2 (HER2/neu) over expression. Aims and Objectives:To highlight the histomorphological spectrum of breast carcinomas and their ER,PR, HER2NEU status. And also to find out correlation between their histological grade and the hormone status . Materials and Methods - 115 breast carcinomas were clinicopathologically and immunohistochemically analyzed in which assessment of Her2/neu, ER, PR had been performed prospectively. Statistical analysis was then used to correlate the above observation. Conclusion: This study highlights the importance of histopathology and immunohistochemistry in breast cancers not only in diagnosing the lesion but also in predicting the prognosis and target therapy.
ABSTRACT
Clear cell breast carcinomas are one of the rare types of invasive carcinoma of the breast. Among them, lipid-rich variant is still rare comprising <1%. The tumor derives its name from the intracytoplasmic neutral lipid that gives the cytoplasm a vacuolated and foamy appearance. These tumors are usually hormone receptors negative and Her-2 Neu positive. Here, we report a case of lipid-rich breast carcinoma which showed hormone receptor positivity and Her-2 Neu negative
ABSTRACT
Objectives: The purpose of the study is to investigate p16 protein expression and promoter methylation of p16 gene and their association with molecular subtypes based on parameter such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Materials and Methods: A total of 114 breast cancer tissue biopsies were collected for methylation-specific polymerase chain reaction (MSP) and immunohistochemical (IHC) analysis. Results: Seven tissue microarrays were constructed. p16 protein expression was studied in 114 cases, of which 35/114 (30.7%) cases showed strong expression and the majority of them had ER-positive tumor (57.6%), and it was statistically significant (P < 0.0074). Similarly, p16 expression was reduced in the majority of PR-negative tumors (83.9%) and the association was statistically significant (P = 0.0026). p16 methylation was studied in 114 cases and was positive in 71.0% cases. Conclusion: High p16 protein expression was associated with ER-positive, PR-negative, and HER2-negative tumors which is associated with poor prognosis. p16 protein expression may be used as a prognostic indicator to predict treatment response to hormonal therapy.