Pathological Features of Breast Cancer seen in Northwestern Tanzania: A Nine Years Retrospective Study.

Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania. This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score), and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15. There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1). About half of the patients (52.4%) were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012). The tumor size ranged from 1 cm to 18 cm in diameter with average (mean) of 5.5 cm (+/- 2.5), and median size of 6 cm. Size of the tumor (above 6 cm in diameter) and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000). Of all patients, 64% were at clinical stage III (specifically IIIB) and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5%) followed by mucinous carcinoma (5.2%), Invasive lobular carcinoma (3%) and in situ ductal carcinoma (0.3%). In all patients, 185 (56.4%) had tumor with histological grade 3. Breast cancer in this region show a trend towards relative young age at diagnosis with advanced stage at diagnosis and high rate of lymph node metastasis. Poor Referral system, lack of screening programs and natural aggressive biological behavior of tumor may contribute to advanced disease at the time of diagnosis

Effects of trade barriers on development and growth

A basic definition of trade barriers could be ‘all factors that influence the amount of goods and services shipped across international borders’ (Feenstra and Taylor, 2017a). This definition is quite neutral, and it needs to be understood that the word ‘barrier’ has a negative connotation, which means that a trade barrier would be any instrument that limits or restrict trade between countries, as opposed to free trade. It is generally accepted that free trade is good for productivity and economic growth, but it is also true that most countries apply some sort of trade restriction, for different reasons

Telomerase activity and telomere length in primary and metastatic tumors from pediatric bone cancer patients

The presence of telomerase activity has been analyzed in almost all tumor types and tumor-derived cell lines. However, there are very few studies that focus on the presence of telomerase activity in bone tumors, and most of them report analysis on very few samples or bone-derived cell lines. The objective of this study was to analyze the telomere length and telomerase activity in primary tumors and metastatic lesions from pediatric osteosarcoma and Ewing's sarcoma patients. The presence of telomerase activity was analyzed by the telomeric repeat amplification protocol assay, and the telomere length was measured by Southern blot. Results were related to survival and clinical outcome. Telomerase activity was detected in 85% of the bone tumor metastases (100% Ewing's sarcomas and 75% osteosarcomas) but only in 12% of the primary tumors (11.1% osteosarcomas and 12.5% Ewing's sarcomas). Bone tumor tissues with telomerase activity had mean telomere lengths 3 kb shorter than those with no detectable telomerase activity (p = 0.041). The presence of telomerase activity was associated with survival (p = 0.009), and longer event-free survival periods were found in patients who lacked telomerase activity compared with those who had detectable telomerase activity levels in their tumor tissues (p = 0.037). The presence of longer telomeres in primary pediatric bone tumors than in metastases could be indicative of alternative mechanisms of lengthening of telomeres for their telomere maintenance rather than telomerase activity. Nevertheless, the activation of telomerase seems to be a crucial step in the malignant progression and acquisition of invasive capability of bone tumors

Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Evaluating the expression of signaling molecule proteins from the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3-kinase (PI3K) pathway in invasive breast cancers may identify prognostic marker(s) associated with early relapse. Methods Immunohistochemical analyses of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), PI3K-p110α, phospho-AKT, phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer. Statistically significant relations between protein expression, clinicopathologic factors, and relapse-free survival (RFS) were analyzed. Results Expression of HSP90 was associated with 5-year RFS, as well as T stage, N stage, histologic grade, estrogen receptor (ER) expression, human epidermal growth factor receptor 2 (HER2) expression, and the Ki-67 proliferation index. On multivariate analysis, coexpression of HSP90 and PI3K-p110α or expression of HSP90 along with PTEN loss demonstrated significantly worse RFS. In subgroup analyses, both exhibited strong prognostic significance in HER2-positive cases, but not in HER2-negative cases. Conclusions The coexpression of HSP90 with PI3K-p110α or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers

Morphometrical malignancy grading is a valuable prognostic factor in invasive ductal breast cancer

The aim of the present study is to augment the prognostic power of breast cancer grading by elaboration of quantitative histopathological methods. We focus on the recently introduced morphometrical grading system in which the three grading sub-features of the WHO grading system are evaluated with the help of computerised nuclear morphometry, and quantitative methods for assessing mitotic activity and tubular differentiation. The prognostic value of the morphometrical grading system is now confirmed in a material of 159 cases of invasive ductal breast cancer. In the current material the morphometrical grading system very efficiently predicted the prognosis of breast cancer by dividing the patients into favourable (grade I), intermediate (grade II), and unfavourable (grade III) outcome (P<0.0001). The morphometrical grading system was especially efficient in identifying patients with the most unfavourable outcome. In our material the morphometrical grade III was associated with a 5.4-fold risk of breast cancer death. In light of the present results, the morphometrical grading can be applied to clinical use as an aid in treatment decisions of patients with invasive ductal breast cancer

The Golden Beauty: Brain Response to Classical and Renaissance Sculptures

Is there an objective, biological basis for the experience of beauty in art? Or is aesthetic experience entirely subjective? Using fMRI technique, we addressed this question by presenting viewers, naïve to art criticism, with images of masterpieces of Classical and Renaissance sculpture. Employing proportion as the independent variable, we produced two sets of stimuli: one composed of images of original sculptures; the other of a modified version of the same images. The stimuli were presented in three conditions: observation, aesthetic judgment, and proportion judgment. In the observation condition, the viewers were required to observe the images with the same mind-set as if they were in a museum. In the other two conditions they were required to give an aesthetic or proportion judgment on the same images. Two types of analyses were carried out: one which contrasted brain response to the canonical and the modified sculptures, and one which contrasted beautiful vs. ugly sculptures as judged by each volunteer. The most striking result was that the observation of original sculptures, relative to the modified ones, produced activation of the right insula as well as of some lateral and medial cortical areas (lateral occipital gyrus, precuneus and prefrontal areas). The activation of the insula was particularly strong during the observation condition. Most interestingly, when volunteers were required to give an overt aesthetic judgment, the images judged as beautiful selectively activated the right amygdala, relative to those judged as ugly. We conclude that, in observers naïve to art criticism, the sense of beauty is mediated by two non-mutually exclusive processes: one based on a joint activation of sets of cortical neurons, triggered by parameters intrinsic to the stimuli, and the insula (objective beauty); the other based on the activation of the amygdala, driven by one's own emotional experiences (subjective beauty)

Gene expression signatures of morphologically normal breast tissue identify basal-like tumors

INTRODUCTION: The role of the cellular microenvironment in breast tumorigenesis has become an important research area. However, little is known about gene expression in histologically normal tissue adjacent to breast tumor, if this is influenced by the tumor, and how this compares with non-tumor-bearing breast tissue. METHODS: To address this, we have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty (n = 44). RESULTS: Based on this data, we determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumor-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumor tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favorable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. CONCLUSION: Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression dataset for comparative studies of tumor expression profiles

Breast cancer prognostic classification in the molecular era: the role of histological grade

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers. © 2010 BioMed Central Lt

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target