MUC1 positive cutaneous metastasis with transepidermal elimination from a breast carcinoma

Breast cancer is the most common cause of cutaneous metastases from internal malignancies. Generally, the neoplastic cells are located in the dermis or hypodermis, while a finding of transepidermal elimination on cutaneous metastases is exceptional. In this report we present a patient with perforating cutaneous metastases from breast cancer with mucin 1 expression. Cutaneous, bone, lung, and hepatic lesions were detected two years after the diagnosis of the primary tumor.Fil: Luna, Amalia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Merino, María Emilia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Alberdi, Cecilio G.. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Segal Eiras, Amada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; ArgentinaFil: Croce, María Virginia. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells

INTRODUCTION: Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells. METHODS: Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5' flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by real-time RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays. RESULTS: We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas. CONCLUSION: Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers

GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells

Introduction Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells. Methods: Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5′ flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by realtime RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays. Results: We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas. Conclusion: Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers.Facultad de Ciencias Médica

MUC1 positive cutaneous metastasis with transepidermal elimination from a breast carcinoma

Breast cancer is the most common cause of cutaneous metastases from internal malignancies. Generally, the neoplastic cells are located in the dermis or hypodermis, while a finding of transepidermal elimination on cutaneous metastases is exceptional. In this report we present a patient with perforating cutaneous metastases from breast cancer with mucin 1 expression. Cutaneous, bone, lung, and hepatic lesions were detected two years after the diagnosis of the primary tumor.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Factors associated with breast cancer in an Argentine city

In Argentina, breast cancer is the most commonly diagnosed cancer and the first leading cause of cancer deaths; this information is mainly based on estimations since only recently, Argentina has organized a National Registry of Tumors. Argentine studies addressing socioeconomic factors and their possible effect on breast cancer prevalence are scarce, and there is not any systematic action to prevent and control breast cancer as well. The aim of this study was to explore the relationship among socioeconomic factors, breast cancer risk factors, women's adherence to mammography screening, and breast cancer prevalence in La Plata, the capital city of Buenos Aires Province (Argentina), an administrative and University city. We performed a cross‐sectional study of women with low socioeconomic power (low group, LG) and a middle group (MG) from October 2012 to December 2012; 739 women between 45 and 79 years old were personally interviewed, being 360 (MG) and 379 (LG). A structured questionnaire previously validated was employed. Variables included were as follows: socioeconomic group, breast cancer risk and socioeconomic factors, mammographic screening parameters, ever diagnosed breast cancer, Physician Enrollment, and Health System which consists of three sectors: Public (free), Private, and Social/Union Security.Centro de Investigaciones Inmunológicas Básicas y Aplicada

The Prognostic Nutritional Index and Nutritional Risk Index Are Associated with Disease Activity in Patients with Systemic Lupus Erythematosus

The prognostic nutritional index (PNI), controlling nutritional status (CONUT) score and nutritional risk index (NRI) have been described as useful screening tools for patient prognosis in several diseases. The aim of this study was to examine the relationship between PNI, CONUT and NRI with clinical disease activity and damage in 173 patients with systemic lupus erythematous (SLE). Disease activity was assessed with the SLE disease activity index (SLEDAI-2K), and disease-related organ damage was assessed using the SLICC/ACR damage index (SDI) damage index. PNI and NRI were significantly lower in active SLE patients than in inactive SLE patients (p < 0.001 and p = 0.012, respectively). PNI was inversely correlated with the SLEDAI score (p < 0.001) and NRI positively correlated with SLEDAI and SDI scores (p = 0.027 and p < 0.001). Linear regression analysis adjusting for age, sex and medications showed that PNI was inversely correlated with SLEDAI ( (95% CI) = -0.176 (-0.254, -0.098), p < 0.001) and NRI positively correlated with SLEDAI ( (95% CI) = 0.056 (0.019, 0.093), p = 0.003) and SDI ( (95% CI) = 0.047 (0.031, 0.063), p < 0.001). PNI (odds ratio (OR) 0.884, 95% confidence interval (CI) 0.809–0.967, p = 0.007) and NRI ((OR) 1.067, 95% CI 1.028–1.108, p = 0.001) were independent predictors of active SLE. These findings suggest that PNI and NRI may be useful markers to identify active SLE in clinical practice.This study was supported by the grant PI0523-2016 from “Consejería de igualdad, salud y políticas sociales” (Junta de Andalucía) and is part of the research group LyDIMED “Lupus y Dieta Mediterránea”. G. Pocovi-Gerardino is a predoctoral fellow from the doctoral program “Medicina clínica y salud pública” of the University of Granad

Patterns of MUC1 tissue expression defined by an Anti-MUC1 cytoplasmic tail monoclonal antibody in breast cancer

Our aim was to determine the pattern of expression of MUC1 mucin cytoplasmic tail (MUC1 CT) in breast carcinoma. A total of 98 invasive breast adenocarcinoma tumor samples were assayed by immunohistochemical (IHC) analysis. The pattern of reaction was classified as membrane, cytoplasmic, or mixed. Subcellular fractions were prepared after SDS-PAGE and Western blotting. The antibodies employed were anti-MUC1 CT (CT2 monoclonal antibody, MAb) and C595 MAb against the extracellular MUC1 core protein. With the CT2 MAb, IHC showed a high percentage of positive staining in 93% of specimens, with membrane staining the most common pattern observed. C595 MAb was reactive in 73% of specimens. Similar percentages of membrane and cytoplasmic staining were found, mainly in a mixed pattern. Western blotting showed different bands. With the CT2 MAb, the membrane fraction showed the most intense reaction; a strong band of reaction was detected at approximately <30 kD. With the C595 MAb, in most cases a double band at 200 kD was found. In breast epithelium, the pattern of MUC1 CT expression may constitute an indicator of MUC1 production because it does not depend on glycosylation. The pattern and extension of MUC1 CT positivity do not vary according to the histopathological subtype of the tumor.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Patterns of MUC1 tissue expression defined by an Anti-MUC1 cytoplasmic tail monoclonal antibody in breast cancer

Our aim was to determine the pattern of expression of MUC1 mucin cytoplasmic tail (MUC1 CT) in breast carcinoma. A total of 98 invasive breast adenocarcinoma tumor samples were assayed by immunohistochemical (IHC) analysis. The pattern of reaction was classified as membrane, cytoplasmic, or mixed. Subcellular fractions were prepared after SDS-PAGE and Western blotting. The antibodies employed were anti-MUC1 CT (CT2 monoclonal antibody, MAb) and C595 MAb against the extracellular MUC1 core protein. With the CT2 MAb, IHC showed a high percentage of positive staining in 93% of specimens, with membrane staining the most common pattern observed. C595 MAb was reactive in 73% of specimens. Similar percentages of membrane and cytoplasmic staining were found, mainly in a mixed pattern. Western blotting showed different bands. With the CT2 MAb, the membrane fraction showed the most intense reaction; a strong band of reaction was detected at approximately <30 kD. With the C595 MAb, in most cases a double band at 200 kD was found. In breast epithelium, the pattern of MUC1 CT expression may constitute an indicator of MUC1 production because it does not depend on glycosylation. The pattern and extension of MUC1 CT positivity do not vary according to the histopathological subtype of the tumor.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Rhomboid domain containing 2 (RHBDD2): A novel cancer-related gene over-expressed in breast cancer

In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n = 46) and immunohistochemistry (n = 213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p = 0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n = 17) or breast benign lesions (n = 16) (p = 0.014). Interestingly, siRNA-mediated silencing of RHBDD2 expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p = 0.001). In addition, analysis of publicly available gene expression data showed a strong association between high RHBDD2 expression and decreased overall survival (p = 0.0023), relapse-free survival (p = 0.0013), and metastasis-free interval (p = 0.006) in patients with primary ER-negative breast carcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression.Facultad de Ciencias Médica

Patients with periodontitis and erectile dysfunction suffer a greater incidence of major adverse cardiovascular events: A prospective study in a Spanish population

DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available because of privacy or ethical restrictions.Background Periodontitis and erectile dysfunction (ED) have been linked with cardiovascular disease. The association of periodontitis and ED with the occurrence of major adverse cardiovascular events has not been previously assessed. The aim of this study was to determine if the presence of periodontitis and ED has any effect on the incidence of major adverse cardiovascular events. Methods Male patients that attended the Urology service were enrolled in a prospective study. Erectile dysfunction was diagnosed according to the International Index of Erectile Function. Sociodemographic data and periodontal clinical parameters were gathered (pocket probing depth, clinical attachment loss, bleeding on probing (BoP), plaque index and number of teeth) at baseline. Major adverse cardiovascular events occurred both before and during the follow-up time were registered. Bivariate analyses, as well as a multivariate analysis were performed, adjusting for potential confounders. Results A total of 158 patients were included, with a mean follow-up of 4.2 years. A greater number of major adverse cardiovascular events occurred in the group that presented periodontitis and ED (P = 0.038). After adjusting by age and previous cardiovascular disease in the multivariate analysis, the annual major adverse cardiovascular event rate was estimated to be 3.7 times higher in the same group (P = 0.049). Other periodontal clinical variables together with ED supported these results and were close to statistical significance. Conclusions Patients with periodontitis and ED, adjusted by age and a cardiovascular disease, showed 3.7 times more risk of suffering major adverse cardiovascular events after mean follow-up of 4.2 years.Research Group #CTS-583 (Junta de Andalucía, Granada, Spain