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Abstract Background The soluble cell adhesion molecules and adipokines are elevated in patients with obesity, hypertension, type 2 diabetes mellitus, breast cancer and atherosclerosis. Objective To investigate the relationship between anthropometric profile, dietary intake, lipid profile and fasting glycemia with serum levels of adipokines (adiponectin and PAI-1) and adhesion molecules (ICAM-1 and VCAM-1) in women without breast cancer undergoing routine mammographic screening. Design Transversal study. Subjects One hundred and forty-five women over 40-years old participated in this study. Results In 39.3% of cases the BMI was above 30 kg/m2; 46.9% had hypertension, 14.5% had type 2 Diabetes Mellitus, 31.7% had dyslipidemia and 88.3% presented a waist-to-hip ratio ≥ 0.8. A linear correlation was found between serum levels of PAI-1 and triglycerides, between serum levels of PAI-1 and WHR and between serum levels of VCAM-1 and BMI. Conclusion We found a high prevalence of obesity and metabolic syndrome. PAI-1 and VCAM-1 levels were correlated with clinical indicators of obesity and overweight.

Abstract Background Breast cancer (BC) is a major public health problem, with rising incidence in many regions of the globe. Although mortality has recently dropped in developed countries, death rates are still increasing in some developing countries, as seen in Brazil. Among the reasons for this phenomenon are the lack of structured screening programs, a long waiting period between diagnosis and treatment, and lack of access to health services for a large proportion of the Brazilian population. Methods and design Since 2004, an intervention study in a cohort of women in Southern Brazil, denominated Porto Alegre Breast Health Intervention Cohort, is being conducted in order to test the effectiveness and cost-effectiveness of a model for BC early detection and treatment. In this study, over 4,000 women from underserved communities aged 40 to 69 years are being screened annually with mammography and clinical breast examination performed by a multidisciplinary team, which also involves nutritional counseling and genetic cancer risk assessment. Risk factors for BC development are also being evaluated. Active search of participants by lay community health workers is one of the major features of our program. The accrual of new participants was concluded in 2006 and the study will last for 10 years. The main goal of the study is to demonstrate significant downstaging of BC in an underserved population through proper screening, attaining a higher rate of early-stage BC diagnoses than usually seen in women diagnosed in the Brazilian Public Health System. Preliminary results show a very high BC incidence in this population (117 cases per 100,000 women per year), despite a low prevalence of classical risk factors. Discussion This study will allow us to test a model of BC early diagnosis and treatment and evaluate its cost-effectiveness in a developing country where the mortality associated with this disease is very high. Also, it might contribute to the evaluation of risk factors in a population with a different ethnic background from that studied in developed countries. If our model is proven effective, it may be replicated in other parts of the globe where BC is also a major public health problem.

Background: Breast cancer (BC) is a major public health problem, with rising incidence in many regions of the globe. Although mortality has recently dropped in developed countries, death rates are still increasing in some developing countries, as seen in Brazil. Among the reasons for this phenomenon are the lack of structured screening programs, a long waiting period between diagnosis and treatment, and lack of access to health services for a large proportion of the Brazilian population.Methods and Design: Since 2004, an intervention study in a cohort of women in Southern Brazil, denominated Porto Alegre Breast Health Intervention Cohort, is being conducted in order to test the effectiveness and cost-effectiveness of a model for BC early detection and treatment. In this study, over 4,000 women from underserved communities aged 40 to 69 years are being screened annually with mammography and clinical breast examination performed by a multidisciplinary team, which also involves nutritional counseling and genetic cancer risk assessment. Risk factors for BC development are also being evaluated. Active search of participants by lay community health workers is one of the major features of our program. The accrual of new participants was concluded in 2006 and the study will last for 10 years. The main goal of the study is to demonstrate significant downstaging of BC in an underserved population through proper screening, attaining a higher rate of early-stage BC diagnoses than usually seen in women diagnosed in the Brazilian Public Health System. Preliminary results show a very high BC incidence in this population (117 cases per 100,000 women per year), despite a low prevalence of classical risk factors.Discussion: This study will allow us to test a model of BC early diagnosis and treatment and evaluate its cost-effectiveness in a developing country where the mortality associated with this disease is very high. Also, it might contribute to the evaluation of risk factors in a population with a different ethnic background from that studied in developed countries. If our model is proven effective, it may be replicated in other parts of the globe where BC is also a major public health problem. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common neoplasm in women worldwide and one of the leading causes of female death. The triple-negative subtype, characterized by the absence of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2), tends to occur in younger patients, be more aggressive and less differentiated. Furthermore, this subtype is considered the most immunogenic and associated with higher levels of tumor cell infiltration, mainly lymphocytes. Tumor-infiltrating lymphocytes (TILs) play a crucial role in the interaction of the host's immune system and cancer cells. The microenvironment is critical in tumor development and progression. Assessment of infiltrating lymphocytes can provide valuable information about the immune response and, given the lack of biomarkers to guide treatment decisions and predict outcomes in triple-negative tumors and can be considered as a potential biomarker. Some evidence suggests that higher levels of these lymphocytes are associated with better responses to systemic treatment, longer progression-free survival and overall survival (OS). However, treatment escalation or de-escalation strategies for triple-negative BC (TNBC) currently do not consider the presence or density of TILs for therapeutic decisions. TILs appear to be useful predictive and prognostic indicators. Further clinical studies are needed to confirm these relationships and integrate TILs as a biomarker consistently into clinical practice. This article summarizes key concepts relating to the role of the immune infiltrate in BC, along with the current status and future prospects regarding TILs as a predictive and prognostic biomarker., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.org/article/view/10.21037/tbcr-23-43/coif). C.H.B. has received grants or contracts to the institution from Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, GSK, Janssen, OBI Pharma, Lilly, Seagen, Roche, BMS, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda, TRIO, PharmaMar, Celgene, PPD, Syneos Health, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, Worldwide, Gilead Sciences, Bayer, Servier; consulting fees from Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, Daiichi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, Astra Zeneca, Zodiac, Lilly, Sanofi, Daiichi; support for attending meetings and/or travel from Novartis, Pfizer, Roche/Genentech, MSD, Astra Zeneca, Lilly, Daiichi; participation on a Data Safety Monitoring Board or Advisory Board from Roche; stock from Thummi and MEDSIR. T.R. has received speaker’s honoraria from Daiichi-Sankyo, AstraZeneca, Gilead Libbs, Pfizer, MSD and Novartis; consulting fees for advisory boards from AstraZeneca, Lilly, MSD and Novartis; research funding from AstraZeneca, FAPESP, Libbs, PRONOM/MS. G.S. has received speaker’s honoraria from Daiichi-Sankyo, AstraZeneca, and Novartis; and consulting fees for advisory boards, and support for attending meetings from AstraZeneca. M.G. has received speaker’s honoraria from Daiichi-Sankyo, AstraZeneca and Novartis; consulting fees for advisory boards from AstraZeneca and Novartis; research funding from AstraZeneca and Libbs. The other authors have no conflicts of interest to declare., (2024 Translational Breast Cancer Research. All rights reserved.)

Background: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS., Methods: A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey., Results: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey., Conclusion: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool.

Introduction: MUTYH-associated polyposis (MAP) is an autosomal recessive cancer predisposition syndrome associated with the development of colorectal tumors and colonic polyps at an early age. MAP syndrome is associated to germline biallelic mutations in the MUTYH gene which lead to deficient DNA repair through the base-excision repair system and accumulation of G:C→T:A transversions. Occurrence of such mutations in oncogenes and tumor suppressor genes drives colorectal carcinogenesis and is associated with the development of colonic polyps. Two common mutations, p.Y179C and p.G396D, are present in approximately 70-80% of MAP in European families with identified MUTYH germline mutations. The aim of this study was to assess the frequency of the germline MUTYH mutations p.Y179C and p.G396D in Brazilian patients with MAP and other hereditary colorectal cancer (CRC) phenotypes, as well as in sporadic CRC cases., Materials and Methods: A total of 75 patients were included. Samples were screened for the MUTYH germline mutations p.Y179C and p.G396D by allelic discrimination assays using allele-specific TaqMan® probes. In all mutation-positive cases, results were confirmed by sequencing., Results and Conclusions: Biallelic germline MUTYH mutations were identified in 4 of 60 (6.6%) patients with a phenotype of hereditary colorectal cancer. Germline MUTYH mutation screening should be considered in the differential diagnosis of hereditary colorectal syndromes, and not only in MAP, but also in familial adenomatous polyposis and Bethesda criteria-positive families. Additional mutation screening studies of the MUTYH gene in a larger number of Brazilian patients will be necessary to confirm these results and determine the validity and applicability of MUTYH mutation screening in our population.

Aims and Background: Basal-like breast cancer is a distinct group of tumors with heterogeneous behavior, and not all have a poor prognosis. The present study analyzed the prevalence and prognosis of early basal-like breast cancer., Methods and Study Design: A total of 112 patients with stage I and II breast cancer were retrospectively analyzed using immunohistochemical stains for estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. Basal-like tumors were defined as being estrogen receptor, progesterone receptor and HER2 negative and cytokeratin 5/6 and/or epidermal growth factor receptor positive., Results: Of the 112 cases, respectively 13 (11.6%) were basal-like, 77 (68.8%) luminal A or B, 13 (11.6%) HER2 positive and 9 (8%) undefined. In basal-like tumors, epidermal growth factor receptor and cytokeratin 5/6 expression was positive in 5 patients (38.5%) and 12 patients (92%), respectively. There was no significant correlation between basal-like breast cancer and age (P = 0.207), lymph node status (P = 1.0) or clinical stage (P = 0.53). Among all tested biomarkers, positivity was found in 81 (72.3%) for estrogen receptor, 13 (11.6%) for HER2, 11 (9.8%) for epidermal growth factor receptor and 36 (32.1%) for cytokeratin 5/6. Epidermal growth factor receptor expression was significantly correlated with estrogen receptor-negative (P = 0.01) and HER2-positive (P = 0.02) tumors. During a median follow-up of 81 months, there were 26 (23%) disease relapses and 12 (10.7%) deaths. No significant difference relating to disease-free survival and overall survival was noted between basal-like breast cancer and subtypes luminal A and B, HER2 positive and undefined., Conclusions: The addition of cytokeratin 5/6 and epidermal growth factor receptor defines a small subgroup of patients with basal-like tumors. In a population with early breast cancer, basal-like tumors did not have a prognosis different from the other subtypes. Neither was there a significant association with clinicopathological features. The high frequency of epidermal growth factor receptor positivity in estrogen receptor-negative and HER2-positive tumors represents a potential target in clinical trials.

The hypothesis tested was that there is an association between the presence of proliferating (MiB-1-positive) cervical cells and clinical outcome of women infected with human immunodeficiency virus (HIV). Female partners (attending the Gynecology Outpatients Clinic of the University Hospital of Rio Grande, Brazil) of known HIV-positive (HIV+) men were used for this pilot study. Among these women, 25 were also HIV+. Papanicolaou smears of these 25 HIV+ women and of 44 HIV- women were graded as negative, CIN I, CIN II, or CIN III, using neural network screening. MiB-1 grading and HPV identification were also performed. The immune status of patients was determined using the current Centers for Disease Control classification. In agreement with the scientific literature, in these Brazilian women both CIN and HPV were associated with HIV. In the HIV+ women, the immune status tends to correlate with MiB-1 grading. Also, in the one case in whom progression from CIN I to invasive cervical carcinoma was observed, the smear contained many MiB-1-positive cells. Staining cervical smears of HIV+ women is a simple procedure to get an indication of clinical outcome of the patient., (Copyright 2001 Wiley-Liss, Inc.)

The post-training IP administration of naloxone (0.8 mg/kg) facilitates memory consolidation of the habituation of a rearing response to a tone in rats. Amphetamine (1.0 - 2.5 mg/kg or nicotine (0.2 - 0.5 mg/kg), and amphetamine (2.5 mg/kg) plus nicotine (0.5 mg/kg) have no effect. The higher doses of amphetamine or nicotine, however, when given together with a dose of naloxone which is ineffective alone (0.2 mg/kg), markedly enhance consolidation. Haloperidol (0.5 mg/kg), propranolol (0.5 mg/kg), and phenoxybenzamine (2.0 mg/kg) have no effect on their own; whereas tolazoline (2.0 mg/kg) impairs consolidation. The effect of naloxone (0.8 mg/kg) is antagonized by haloperidol and by propranolol, but not by phenoxybenzamine or tolazoline. The results suggest that naloxone causes memory facilitation through the release of central dopaminergic and beta-adrenergic mechanisms from a tonic inhibitory influence of endogenous opiate peptide systems.

Degos disease is a rare disorder, characterized by a vasculopathy of unknown origin that leads to typical skin lesions and involves other organ systems. It is frequently a lethal condition; death occurs as a consequence of intestinal perforation. In about 20% of cases, the central nervous system is involved and the neurological symptoms can be prominent. The incidence of the disease in children is very uncommon. We report the case of teenage girl who had Degos disease with prominent neurological involvement.

A case of epidermoid carcinoma with metastasis to a cervical lymph node is reported. Due to an intense granulomatous reaction and the similarity of the neoplastic cells with the epithelioid cells there was diagnostic difficulty when based only on histology and fine needle aspiration cytology. The utilization of electron microscopy and immunoperoxidase defined the diagnosis. Discussion is made about the importance of the utilization of multiples methods in surgical pathology and the pathogenesis of the granulomatous reaction associated with malignant neoplasms.