Grading of invasive breast carcinoma: the way forward

Histologic grading has been a simple and inexpensive method to assess tumor behavior and prognosis of invasive breast cancer grading, thereby identifying patients at risk for adverse outcomes, who may be eligible for (neo)adjuvant therapies. Histologic grading needs to be performed accurately, on properly fixed specimens, and by adequately trained dedicated pathologists that take the time to diligently follow the protocol methodology. In this paper, we review the history of histologic grading, describe the basics of grading, review prognostic value and reproducibility issues, compare performance of grading to gene expression profiles, and discuss how to move forward to improve reproducibility of grading by training, feedback and artificial intelligence algorithms, and special stains to better recognize mitoses. We conclude that histologic grading, when adequately carried out, remains to be of important prognostic value in breast cancer patients

Применение генетического алгоритма в задачах адаптации структур данных

Представлена разработанная схема адаптации структур данных в оперативной памяти. Для поиска адаптированной структуры данных предложено применение генетического алгоритма. Определены его особенности. Для растровых изображений с соответствующими заголовками выполнены экспериментальные исследования временной эффективности адаптированных структур данных, времени сходимости генетического алгоритма и условия целесообразности применения адаптации.Представлена розроблена схема адаптації структур даних в оперативній пам’яті. Для пошуку адаптованої структури даних запропоновано застосування генетичного алгоритму. Визначені його особливості. Для растрових зображень з відповідними заголовками виконані експериментальні дослідження часової ефективності адаптованих структур даних, часу збіжності генетичного алгоритму та умови доцільності застосування адаптації.The developed scheme of data structures adaptation in memory is given. To search for an adapted data structure, genetic algorithm is proposed and its characteristics are defined. For raster images with the appropriate headings, experimental studies of the time efficiency of adapted data structures, the convergence time of the genetic algorithm and conditions for feasibility of adapting are performed

Loss of expression of FANCD2 protein in sporadic and hereditary breast cancer

Fanconi anemia (FA) is a recessive disorder associated with progressive pancytopenia, multiple developmental defects, and marked predisposition to malignancies. FA is genetically heterogeneous, comprising at least 12 complementation groups (A–M). Activation of one of the FA proteins (FANCD2) by mono-ubiquitination is an essential step in DNA damage response. As FANCD2 interacts with BRCA1, is expressed in proliferating normal breast cells, and FANCD2 knockout mice develop breast tumors, we investigated the expression of FANCD2 in sporadic and hereditary invasive breast cancer patients to evaluate its possible role in breast carcinogenesis. Two tissue microarrays of 129 and 220 sporadic breast cancers and a tissue microarray containing 25 BRCA1 germline mutation-related invasive breast cancers were stained for FANCD2. Expression results were compared with several clinicopathological variables and tested for prognostic value. Eighteen of 96 (19%) sporadic breast cancers and two of 21 (10%) BRCA1-related breast cancers were completely FANCD2-negative, which, however, still showed proliferation. In the remaining cases, the percentage of FANCD2-expressing cells correlated strongly with mitotic index and percentage of cells positive for the proliferation markers Ki-67 and Cyclin A. In immunofluorescence double staining, coexpression of FANCD2 and Ki-67 was apparent. In survival analysis, high FANCD2 expression appeared to be prognostically unfavorable for overall survival (p = 0.03), independent from other major prognosticators (p = 0.026). In conclusion, FANCD2 expression is absent in 10–20% of sporadic and BRCA1-related breast cancers, indicating that somatic inactivating (epi)genetic events in FANCD2 may be important in both sporadic and hereditary breast carcinogenesis. FANCD2 is of independent prognostic value in sporadic breast cancer

Закономерности распределения аномальных концентраций гелия в палеозойских отложениях Донбасса

Підвищені концентрації гелію у вільних і розчинених газах у вугільно-породному масиві Донбасу приурочені до зон зчленування Донбасу з Приазовським і Воронезьким кристалічними масивами і Головної антикліналі. Диз'юнктивні тектонічні порушення глибокого закладення служили, ймовірно, шляхами транзиту гелію від кристалічних порід фундаменту в палеозойські відклади Донбасу, і підвищений вміст гелію може служити індикатором шляхів транзиту газів з глибоких горизонтів Донецького вугільного басейну.Elevated concentrations of helium in free and dissolved gases in coal-rock mass of the Donets Coal Basin are confined to the junction zones of the Donets Coal Basin with the Priazovie and Voronezh crystalline core-areas and Glavnaya (Principal) Anticline. Deep-laid disjunctive dislocations were probably the ways for transit of helium from crystalline basement rocks into Paleozoic deposits of the Basin. Elevated concentrations of helium can also serve as indicators of the ways for transit of gases from deep levels of the Donets Coal Basin

Expression of hypoxia-inducible factor-1α and cell cycle proteins in invasive breast cancer are estrogen receptor related

BACKGROUND: The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key regulator of the cellular response to hypoxia. Previous studies showed that concentrations of its subunit HIF-1α, as a surrogate for HIF-1 activity, are increased during breast carcinogenesis and can independently predict prognosis in breast cancer. During carcinogenesis, the cell cycle is progressively deregulated, and proliferation rate is a strong prognostic factor in breast cancer. In this study we undertook a detailed evaluation of the relationships between HIF-1α and cell cycle-associated proteins. METHODS: In a representative estrogen receptor (ER) group of 150 breast cancers, the expression of HIF-1α, vascular endothelial growth factor, the ER, HER-2/neu, Ki-67, cyclin A, cyclin D(1), p21, p53, and Bcl-2 was investigated by immunohistochemistry. RESULTS: High concentrations (5% or more) of HIF-1α were associated with increased proliferation as shown by positive correlations with Ki-67 (P < 0.001) and the late S–G2-phase protein cyclin A (P < 0.001), but not with the G1-phase protein cyclin D(1). High HIF-1α concentrations were also strongly associated with p53 positivity (P < 0.001) and loss of Bcl-2 expression (P = 0.013). No association was found between p21 and HIF-1α (P = 0.105) in the whole group of patients. However, the subgroup of ER-positive cancers was characterized by a strong positive association between HIF-1α and p21 (P = 0.023), and HIF-1α lacked any relation with proliferation. CONCLUSION: HIF-1α overexpression is associated with increased proliferation, which might explain the adverse prognostic impact of increased concentrations of HIF-1α in invasive breast cancer. In ER-positive tumors, HIF-1α is associated with p21 but not against proliferation. This shows the importance of further functional analysis to unravel the role of HIF-1 in late cell cycle progression, and the link between HIF-1, p21, and ER

Meta-analysis and cost-effectiveness of ductoscopy, duct excision surgery and MRI for the diagnosis and treatment of patients with pathological nipple discharge

INTRODUCTION: Pathological nipple discharge (PND) is a common breast-related complaint for referral to a surgical breast clinic because of its association with breast cancer. The aim of this meta-analysis was to compare the diagnostic efficacy of magnetic resonance imaging (MRI) and ductoscopy in patients with PND. Additionally, we determined the most cost-efficient strategy for the treatment of PND and the detection of breast cancer in PND patient without radiological suspicion for malignancy. MATERIALS AND METHODS: PubMed and EMBASE were searched to collect the relevant literature from the inception of both diagnostic methods until January 27th 2020. The search yielded 815 original citations, of which 10 studies with 894 patients were finally included for analysis. Costs of ductoscopy, MRI and duct excision surgery were obtained from the UMC Utrecht as established in the year 2019. These costs included: medical personnel, overhead costs, material costs and sterilisation costs. RESULTS: The meta-analysis showed no significant difference in sensitivity between ductoscopy (44%) and MRI (76%) for the detection of malignancy in patients with PND. However, ductoscopy (98%) had a statistically significantly higher specificity than MRI (84%). Individual costs were €1401.33, €822.13 and €6494.27 for ductoscopy, MRI and duct excision surgery, respectively. Full diagnostic strategy involving ductoscopy was on average €1670.97, while with MRI it was €2070.27. CONCLUSION: Patients undergoing MRI are more often (false) positive which more often leads to duct excision surgery referrals compared to ductoscopy. This makes ductoscopy significantly more cost-effective compared MRI in patients with PND without radiological suspicion for malignancy

The Physiological MicroRNA Landscape in Nipple Aspirate Fluid: Differences and Similarities with Breast Tissue, Breast Milk, Plasma and Serum

BACKGROUND: MicroRNAs (miRNAs) target 60% of human messenger RNAs and can be detected in tissues and biofluids without loss of stability during sample processing, making them highly appraised upcoming biomarkers for evaluation of disease. However, reporting of the abundantly expressed miRNAs in healthy samples is often surpassed. Here, we characterized for the first time the physiological miRNA landscape in a biofluid of the healthy breast: nipple aspirate fluid (NAF), and compared NAF miRNA expression patterns with publically available miRNA expression profiles of healthy breast tissue, breast milk, plasma and serum. METHODS: MiRNA RT-qPCR profiling of NAF (n = 41) and serum (n = 23) samples from two healthy female cohorts was performed using the TaqMan OpenArray Human Advanced MicroRNA 754-Panel. MiRNA quantification data based on non-targeted or multi-targeted profiling techniques for breast tissue, breast milk, plasma and serum were retrieved from the literature by means of a systematic search. MiRNAs from each individual study were orderly ranked between 1 and 50, combined into an overall ranking per sample type and compared. RESULTS: NAF expressed 11 unique miRNAs and shared 21/50 miRNAs with breast tissue. Seven miRNAs were shared between the five sample types. Overlap between sample types varied between 42% and 62%. Highly ranked NAF miRNAs have established roles in breast carcinogenesis. CONCLUSION: This is the first study to characterize and compare the unique physiological NAF-derived miRNA landscape with the physiological expression pattern in breast tissue, breast milk, plasma and serum. Breast-specific sources did not mutually overlap more than with systemic sources. Given their established role in carcinogenesis, NAF miRNA assessment could be a valuable tool in breast tumor diagnostics

Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report

Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two different primary malignancies. A 51 year-old woman with a previous history of bilateral breast cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune suppression on lymphoid cells by oesophageal carcinoma cells, are discussed