Number of apoptotic cells as a prognostic marker in invasive breast cancer

Apoptosis plays an important role in tumorigenesis. Tumour growth is determined by the rate of cell proliferation and cell death. We counted the number of apoptotic cells in haematoxylin and eosin (H&E)-stained tumour sections in series of 172 grade I and II invasive breast cancers with long-term follow-up. The number of apoptotic cells in ten high-power fields were converted to the number of apoptotic cells per mm2to obtain the apoptotic index (AI). The AI showed a positive correlation to the mitotic activity index (MAI) (P = 0.0001), histological grade (P< 0.0001) and worse tumour differentiation. Patients with high AI showed shorter overall survival than patients with low AI in the total group as well as in the lymph node-positive group. Tumour size, MAI, lymph node status and AI were independent prognostic indicators in multivariate analysis. The AI was shown to be of additional prognostic value to the MAI in the total patients group as well as in the lymph node-positive group. The correlation between the AI and the MAI points to linked mechanisms of apoptosis and proliferation. Since apoptotic cells can be counted with good reproducibility in H&E-stained tumour sections, the AI may be used as an additional prognostic indicator in invasive breast cancer. © 2000 Cancer Research Campaig

The association of socioeconomic status on treatment strategy in patients with stage I and II breast cancer in the Netherlands

BACKGROUND: Previous studies have shown that socioeconomic status (SES) influences breast cancer therapy. However, these studies were performed in countries with unequal access to healthcare. Therefore, the aim of this study is to investigate whether SES also contributes to the likelihood of receiving a certain therapy in the Netherlands, a country with supposedly equal access to healthcare. MATERIALS AND METHODS: From the Netherlands Cancer Registry, 105,287 patients with newly diagnosed stage I or II breast cancer diagnosed between 2011 and 2018 were selected for analysis. SES was calculated from the average incomes of each postal code, which were divided into 10 deciles. Primary outcome was the effect of SES on the likelihood of undergoing surgery and secondary outcome was the effect of SES on the likelihood of the type of surgery. Both outcomes were corrected for patient, tumor, and hospital characteristics and were expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: SES did not affect the likelihood of a breast cancer patient to undergo surgery (OR 1.00 per 10% stratum). In contrast, increased age and higher tumor stage were the most important factors determining whether patients underwent surgery. Patients with higher SES were less likely to undergo mastectomy (OR 0.98). Additionally, more recently diagnosed patients were less likely to undergo mastectomy (OR 0.93 per year) while patients with higher tumor stage were more likely to undergo mastectomy (OR 3.42). CONCLUSION: SES does not affect whether a patient undergoes surgery; however, higher SES increased the likelihood of BCT

Expression of hypoxia-induced proteins in ductal carcinoma in situ and invasive cancer of the male breast

AIMS: The aim of this study was to determine the role of hypoxia in male breast carcinogenesis by evaluating the expression of the hypoxia-related proteins, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase IX (CAIX) and glucose transporter-1 (Glut-1), in ductal carcinoma in situ (DCIS) of the male breast in relation to invasive cancer (IC). METHODS: Tumour tissue blocks of 18 cases of pure DCIS, 58 DCIS cases adjacent to IC (DCIS-AIC) and the 58 IC cases were stained by immunohistochemistry for HIF-1α, CAIX and Glut-1, and expression frequencies and patterns (diffuse and/or perinecrotic) were noted. RESULTS: HIF-1α overexpression was observed in 61.1% (11/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 36.2% (21/58) of IC cases (not significant (n.s.)). CAIX overexpression was observed in 16.7% (3/18) of pure DCIS, in 37.9% (22/58) of DCIS-AIC and in 24.1% (14/58) of IC cases (n.s.). Glut-1 overexpression was observed in 61.1% (11/18) of pure DCIS, in 75.9% (44/58) of DCIS-AIC and in 62.1% (36/58) of IC cases (n.s.). Expression of hypoxia-related proteins was seen around necrosis in a little over one-third of DCIS cases, and often coincided with expression in adjacent IC when present. All these observations indicate that the hypoxia response is already at its maximum in the preinvasive DCIS stage. CONCLUSIONS: In conclusion, male DCIS frequently shows activated hypoxia response, comparable to male IC. This indicates that the activated hypoxia response previously seen in male IC is not a late bystander but likely a genuine carcinogenetic event

Hypoxia-Inducible Factor-1 as a Therapeutic Target in Endometrial Cancer Management

In the Western world, endometrial cancer (EC) is the most common malignant tumor of the female genital tract. Solid tumors like EC outgrow their vasculature resulting in hypoxia. Tumor hypoxia is important because it renders an aggressive phenotype and leads to radio- and chemo-therapy resistance. Hypoxia-inducible factor-1α (HIF-1α) plays an essential role in the adaptive cellular response to hypoxia and is associated with poor clinical outcome in EC. Therefore, HIF-1 could be an attractive therapeutic target. Selective HIF-1 inhibitors have not been identified. A number of nonselective inhibitors which target signaling pathways upstream or downstream HIF-1 are known to decrease HIF-1α protein levels. In clinical trials for the treatment of advanced and/or recurrent EC are the topoisomerase I inhibitor Topotecan, mTOR-inhibitor Rapamycin, and angiogenesis inhibitor Bevacizumab. Preliminary data shows encouraging results for these agents. Further work is needed to identify selective HIF-1 inhibitors and to translate these into clinical trials

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

Особенности деонтологии в сексологической практике

Описаны основные принципы врачебной этики в сексологической практике. Рассмотрены особенности взаимоотношений врача−сексолога и пациента. Подчеркивается, что выполнение врачом деонтологических принципов будет способствовать гармонизации семейно−сексуальных отношений.Basic principles of medical ethics in sexological practice are presented. The peculiarities of mutual relations of the doctor sexologist and the patient are discussed. It is emphasized that adherence of the doctor−sexologist of ethical principles will promote harmonization of family sexual relations

Deep Learning-Based Grading of Ductal Carcinoma In Situ in Breast Histopathology Images

Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that can progress into invasive ductal carcinoma (IDC). Studies suggest DCIS is often overtreated since a considerable part of DCIS lesions may never progress into IDC. Lower grade lesions have a lower progression speed and risk, possibly allowing treatment de-escalation. However, studies show significant inter-observer variation in DCIS grading. Automated image analysis may provide an objective solution to address high subjectivity of DCIS grading by pathologists. In this study, we developed a deep learning-based DCIS grading system. It was developed using the consensus DCIS grade of three expert observers on a dataset of 1186 DCIS lesions from 59 patients. The inter-observer agreement, measured by quadratic weighted Cohen's kappa, was used to evaluate the system and compare its performance to that of expert observers. We present an analysis of the lesion-level and patient-level inter-observer agreement on an independent test set of 1001 lesions from 50 patients. The deep learning system (dl) achieved on average slightly higher inter-observer agreement to the observers (o1, o2 and o3) ($\kappa_{o1,dl}=0.81, \kappa_{o2,dl}=0.53, \kappa_{o3,dl}=0.40$) than the observers amongst each other ($\kappa_{o1,o2}=0.58, \kappa_{o1,o3}=0.50, \kappa_{o2,o3}=0.42$) at the lesion-level. At the patient-level, the deep learning system achieved similar agreement to the observers ($\kappa_{o1,dl}=0.77, \kappa_{o2,dl}=0.75, \kappa_{o3,dl}=0.70$) as the observers amongst each other ($\kappa_{o1,o2}=0.77, \kappa_{o1,o3}=0.75, \kappa_{o2,o3}=0.72$). In conclusion, we developed a deep learning-based DCIS grading system that achieved a performance similar to expert observers. We believe this is the first automated system that could assist pathologists by providing robust and reproducible second opinions on DCIS grade