Enhancing AI Research for Breast Cancer: A Comprehensive Review of Tumor-Infiltrating Lymphocyte Datasets.

The field of immunology is fundamental to our understanding of the intricate dynamics of the tumor microenvironment. In particular, tumor-infiltrating lymphocyte (TIL) assessment emerges as essential aspect in breast cancer cases. To gain comprehensive insights, the quantification of TILs through computer-assisted pathology (CAP) tools has become a prominent approach, employing advanced artificial intelligence models based on deep learning techniques. The successful recognition of TILs requires the models to be trained, a process that demands access to annotated datasets. Unfortunately, this task is hampered not only by the scarcity of such datasets, but also by the time-consuming nature of the annotation phase required to create them. Our review endeavors to examine publicly accessible datasets pertaining to the TIL domain and thereby become a valuable resource for the TIL community. The overall aim of the present review is thus to make it easier to train and validate current and upcoming CAP tools for TIL assessment by inspecting and evaluating existing publicly available online datasets.

Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.

Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response.

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.

Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma.

BACKGROUND: To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC). METHODS: We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery. RESULTS: Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%-53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%-76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086). CONCLUSION: In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

CD68 and CD83 immune populations in non-metastatic axillary lymph nodes are of prognostic value for the survival and relapse of breast cancer patients.

BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.

How the variability between computer-assisted analysis procedures evaluating immune markers can influence patients' outcome prediction.

Differences between computer-assisted image analysis (CAI) algorithms may cause discrepancies in the identification of immunohistochemically stained immune biomarkers in biopsies of breast cancer patients. These discrepancies have implications for their association with disease outcome. This study aims to compare three CAI procedures (A, B and C) to measure positive marker areas in post-neoadjuvant chemotherapy biopsies of patients with triple-negative breast cancer (TNBC) and to explore the differences in their performance in determining the potential association with relapse in these patients. A total of 3304 digital images of biopsy tissue obtained from 118 TNBC patients were stained for seven immune markers using immunohistochemistry (CD4, CD8, FOXP3, CD21, CD1a, CD83, HLA-DR) and were analyzed with procedures A, B and C. The three methods measure the positive pixel markers in the total tissue areas. The extent of agreement between paired CAI procedures, a principal component analysis (PCA) and Cox multivariate analysis was assessed. Comparisons of paired procedures showed close agreement for most of the immune markers at low concentration. The probability of differences between the paired procedures B/C and B/A was generally higher than those observed in C/A. The principal component analysis, largely based on data from CD8, CD1a and HLA-DR, identified two groups of patients with a significantly lower probability of relapse than the others. The multivariate regression models showed similarities in the factors associated with relapse for procedures A and C, as opposed to those obtained with procedure B. General agreement among the results of CAI procedures would not guarantee that the same predictive breast cancer markers were consistently identified. These results highlight the importance of developing additional strategies to improve the sensitivity of CAI procedures.

Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial.

BACKGROUND: The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator. METHODS: Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations. RESULTS: In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival. CONCLUSIONS: In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.

Succinate Pathway in Head and Neck Squamous Cell Carcinoma: Potential as a Diagnostic and Prognostic Marker.

Head and neck squamous cell carcinoma (HNSCC) is characterized by high rates of mortality and treatment-related morbidity, underscoring the urgent need for innovative and safe treatment strategies and diagnosis practices. Mitochondrial dysfunction is a hallmark of cancer and can lead to the accumulation of tricarboxylic acid cycle intermediates, such as succinate, which function as oncometabolites. In addition to its role in cancer development through epigenetic events, succinate is an extracellular signal transducer that modulates immune response, angiogenesis and cell invasion by activating its cognate receptor SUCNR1. Here, we explored the potential value of the circulating succinate and related genes in HNSCC diagnosis and prognosis. We determined the succinate levels in the serum of 66 pathologically confirmed, untreated patients with HNSCC and 20 healthy controls. We also surveyed the expression of the genes related to succinate metabolism and signaling in tumoral and nontumoral adjacent tissue and in normal mucosa from 50 patients. Finally, we performed immunohistochemical analysis of SUCNR1 in mucosal samples. The results showed that the circulating levels of succinate were higher in patients with HNSCC than in the healthy controls. Additionally, the expression of SUCNR1, HIF-1α, succinate dehydrogenase (SDH) A, and SDHB was higher in the tumor tissue than in the matched normal mucosa. Consistent with this, immunohistochemical analysis revealed an increase in SUCNR1 protein expression in tumoral and nontumoral adjacent tissue. High SUCNR1 and SDHA expression levels were associated with poor locoregional control, and the locoregional recurrence-free survival rate was significantly lower in patients with high SUCNR1 and SDHA expression than in their peers with lower levels (77.1% [95% CI: 48.9-100.0] vs. 16.7% [95% CI: 0.0-44.4], p = 0.018). Thus, the circulating succinate levels are elevated in HNSCC and high SUCNR1/SDHA expression predicts poor locoregional disease-free survival, identifying this oncometabolite as a potentially valuable noninvasive biomarker for HNSCC diagnosis and prognosis.

System for quantitative evaluation of DAB&H-stained breast cancer biopsy digital images (CHISEL).

This study presents CHISEL (Computer-assisted Histopathological Image Segmentation and EvaLuation), an end-to-end system capable of quantitative evaluation of benign and malignant (breast cancer) digitized tissue samples with immunohistochemical nuclear staining of various intensity and diverse compactness. It stands out with the proposed seamless segmentation based on regions of interest cropping as well as the explicit step of nuclei cluster splitting followed by a boundary refinement. The system utilizes machine learning and recursive local processing to eliminate distorted (inaccurate) outlines. The method was validated using two labeled datasets which proved the relevance of the achieved results. The evaluation was based on the IISPV dataset of tissue from biopsy of breast cancer patients, with markers of T cells, along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients. Based on the comparison of the ground truth with the results of the detected and classified objects, we conclude that the proposed method can achieve better or similar results as the state-of-the-art methods. This system deals with the complex problem of nuclei quantification in digitalized images of immunohistochemically stained tissue sections, achieving best results for DAB&H-stained breast cancer tissue samples. Our method has been prepared with user-friendly graphical interface and was optimized to fully utilize the available computing power, while being accessible to users with fewer resources than needed by deep learning techniques.

Differences in the Immune Response of the Nonmetastatic Axillary Lymph Nodes between Triple-Negative and Luminal A Breast Cancer Surrogate Subtypes.

Breast cancer (BC) comprises four immunohistochemical surrogate subtypes of which triple-negative breast cancer (TNBC) has the highest risk of mortality. Axillary lymph nodes (ALNs) are the regions where BC cells first establish before distant metastasis, and the presence of tumor cells in the ALN causes an immune tolerance profile that contrasts with that of the nonmetastatic ALN (ALN-). However, few studies have compared the immune components of the ALNs- in BC subtypes. The present study aimed to determine whether differences between immune populations in the primary tumor and ALNs- were associated with the luminal A or TNBC subtype. We evaluated a retrospective cohort of 144 patients using paraffin-embedded biopsies. The TNBC samples tended to have a higher histologic grade and proliferation index and had higher levels of immune markers compared with luminal A in primary tumors and ALNs-. Two methods for validating the multivariate analysis found that histologic grade, intratumoral S100 dendritic cells, and CD8 T lymphocytes and CD57 natural killer cells in the ALNs- were factors associated with TNBC, whereas CD83 dendritic cells in the ALNs- were associated with the luminal A subtype. In conclusion, we found that intratumoral regions and ALNs- of TNBC contained higher concentrations of markers related to immune tolerance than luminal A. This finding partially explains the worse prognosis of patients with TNBC.

Peritumoral immune infiltrates in primary tumours are not associated with the presence of axillary lymph node metastasis in breast cancer: a retrospective cohort study.

BACKGROUND: The axillary lymph nodes (ALNs) in breast cancer patients are the body regions to where tumoral cells most often first disseminate. The tumour immune response is important for breast cancer patient outcome, and some studies have evaluated its involvement in ALN metastasis development. Most studies have focused on the intratumoral immune response, but very few have evaluated the peritumoral immune response. The aim of the present article is to evaluate the immune infiltrates of the peritumoral area and their association with the presence of ALN metastases. METHODS: The concentration of 11 immune markers in the peritumoral areas was studied in 149 patients diagnosed with invasive breast carcinoma of no special type (half of whom had ALN metastasis at diagnosis) using tissue microarrays, immunohistochemistry and digital image analysis procedures. The differences in the concentration of the immune response of peritumoral areas between patients diagnosed with and without metastasis in their ALNs were evaluated. A multivariate logistic regression model was developed to identify the clinical-pathological variables and the peritumoral immune markers independently associated with having or not having ALN metastases at diagnosis. RESULTS: No statistically significant differences were found in the concentrations of the 11 immune markers between patients diagnosed with or without ALN metastases. Patients with metastases in their ALNs had a higher histological grade, more lymphovascular and perineural invasion and larger-diameter tumours. The multivariate analysis, after validation by bootstrap simulation, revealed that only tumour diameter (OR = 1.04; 95% CI [1.00-1.07]; p = 0.026), lymphovascular invasion (OR = 25.42; 95% CI [9.57-67.55]; p < 0.001) and histological grades 2 (OR = 3.84; 95% CI [1.11-13.28]; p = 0.033) and 3 (OR = 5.18; 95% CI [1.40-19.17]; p = 0.014) were associated with the presence of ALN metastases at diagnosis. This study is one of the first to study the association of the peritumoral immune response with ALN metastasis. We did not find any association of peritumoral immune infiltrates with the presence of ALN metastasis. Nevertheless, this does not rule out the possibility that other peritumoral immune populations are associated with ALN metastasis. This matter needs to be examined in greater depth, broadening the types of peritumoral immune cells studied, and including new peritumoral areas, such as the germinal centres of the peritumoral tertiary lymphoid structures found in extensively infiltrated neoplastic lesions.

The Immune Response in Nonmetastatic Axillary Lymph Nodes Is Associated with the Presence of Axillary Metastasis and Breast Cancer Patient Outcome.

Tumor cells can modify the immune response in primary tumors and in the axillary lymph nodes with metastasis (ALN+) in breast cancer (BC), influencing patient outcome. We investigated whether patterns of immune cells in the primary tumor and in the axillary lymph nodes without metastasis (ALN-) differed between patients diagnosed without ALN+ (diagnosed-ALN-) and with ALN+ (diagnosed-ALN+) and the implications for clinical outcome. Eleven immune markers were studied using immunohistochemistry, tissue microarray, and digital image analysis in 141 BC patient samples (75 diagnosed-ALN+ and 66 diagnosed-ALN-). Two logistic regression models were derived to identify the clinical, pathologic, and immunologic variables associated with the presence of ALN+ at diagnosis. There are immune patterns in the ALN- associated with the presence of ALN+ at diagnosis. The regression models revealed a small subgroup of diagnosed-ALN+ with ALN- immune patterns that were more similar to those of the ALN- of the diagnosed-ALN-. This small subgroup also showed similar clinical behavior to that of the diagnosed-ALN-. Another small subgroup of diagnosed-ALN- with ALN- immune patterns was found whose members were more similar to those of the ALN- of the diagnosed-ALN+. This small subgroup had similar clinical behavior to the diagnosed-ALN+. These data suggest that the immune response present in ALN- at diagnosis could influence the clinical outcome of BC patients.

Immune response profile of primary tumour, sentinel and non-sentinel axillary lymph nodes related to metastasis in breast cancer: an immunohistochemical point of view.

Approximately 1.67 million new cases of breast cancer (BC) are diagnosed annually, and patient survival significantly decreases when the disease metastasizes. The axillary lymph nodes (ALNs) are the main doorway for BC tumoral cell escape, through which cells can disseminate to distant organs. The immune response, which principally develops in the lymph nodes, is linked to cancer progression, and its efficacy at controlling tumoral growth is compromised during the disease. Immunohistochemistry (IHC) is one of the most widely used research techniques for studying the immune response. It allows the measurement of the expression of particular markers related to the immune populations. This review focuses on the role of the immune populations in the primary tumour in the locoregional metastasis of the ALN, and the relationship of the immune response in these regions to distant metastasis. We considered only studies of immune cells using IHC techniques. In particular, lymphocytes, macrophages and dendritic cells all play important roles in BC and have been extensively studied. Although further research is needed, there is much evidence of their role in the invasion of the ALN and distant organs. Their association with tumoral growth or protection has not yet been demonstrated decisively and is very likely to be determined by a combination of factors. Moreover, even though IHC is a widely used technique in cancer diagnosis and research, there is still room for improvement, since its quantification needs to be properly standardized.

Violence and depression in a community sample.

AIMS AND OBJECTIVES: To understand the relation between the experience of violence and sociodemographic and clinical factors, and to determine whether diagnosed depression and the presence of anxiety and stress are related to having experienced workplace and domestic violence in different genders and age groups. BACKGROUND: Previous studies indicate that domestic and workplace violence increase the risk of suffering from depression. However, no studies have evaluated these two types of violence in a same cohort. DESIGN AND METHODS: We designed a descriptive cross-sectional study from 317 individuals randomly selected from the population in southern Catalonia (Spain). Sociodemographic and Goldberg anxiety-depression questionnaires were administered by telephone survey to 160 men and 157 women in December 2008. The data obtained were analysed by a logistic regression model. RESULTS: A quarter of the individuals had suffered from violence: 48·29% of them had experienced domestic violence and 32·9% had experienced workplace violence. Nearly half of the individuals with depression had experienced violence. No statistical difference has been observed between domestic and workplace violence regarding diagnosed depression. Women were twice as likely as men to have suffered from violence. People working outside their home and those who claimed to have no social support had a greater risk of suffering from violence. A greater consumption of medication, above all of psychotropic drugs, is associated with experiencing violence and with greater comorbidity. Predictive factors for suffering from depression are being women, having experienced violence, having suffered stress or anxiety, having little or no social support, having overload of task or having no secondary education and no tertiary education. CONCLUSIONS: This study suggests that when considering depression, anxiety and stress, especially in women, we must take into account whether an individual has suffered violence. RELEVANCE TO CLINICAL PRACTICE: Identifying violence can help health professionals, managers and researchers improve care and reduce suffering in families and communities.

Evaluation of cytokeratin-19 in breast cancer tissue samples: a comparison of automatic and manual evaluations of scanned tissue microarray cylinders.

BACKGROUND: Digital image (DI) analysis avoids visual subjectivity in interpreting immunohistochemical stains and provides more reproducible results. An automated procedure consisting of two variant methods for quantifying the cytokeratin-19 (CK19) marker in breast cancer tissues is presented. METHODS: The first method (A) excludes the holes inside selected CK19 stained areas, and the second (B) includes them. 93 DIs scanned from complete cylinders of tissue microarrays were evaluated visually by two pathologists and by the automated procedures. RESULTS AND CONCLUSIONS: There was good concordance between the two automated methods, both of which tended to identify a smaller CK19-positive area than did the pathologists. The results obtained with method B were more similar to those of the pathologists; probably because it takes into account the entire positive tumoural area, including the holes. However, the pathologists overestimated the positive area of CK19. Further studies are needed to confirm the utility of this automated procedure in prognostic studies.

Development of automated quantification methodologies of immunohistochemical markers to determine patterns of immune response in breast cancer: a retrospective cohort study.

INTRODUCTION: Lymph nodes are one of the main sites where an effective immune response develops. Normally, axillary nodes are the first place where breast cancer produces metastases. Several studies have demonstrated the importance of immune cells, especially dendritic cells, in the evolution of breast cancer. The goal of the project is to identify differences in the patterns of immune infiltrates, with particular emphasis on dendritic cells, in tumour and axillary node biopsies between patients with and without metastases in the axillary nodes at the time of diagnosis. It is expected that these differences will be able to explain differences in survival, relapse and clinicopathological variables between the two groups. METHODS AND ANALYSIS: The study will involve 100 patients diagnosed with invasive breast cancer between 2000 and 2007, 50% of whom have metastases in the axillary lymph node at diagnosis. In selected patients, two cylinders from biopsies of representative areas of tumour and axillary nodes (with and without metastasis) will be selected and organised in tissue microarrays. Samples will be stained using immunohistochemical techniques for different markers of immune response and dendritic cells. Two images of each cylinder will be captured under standardised conditions for each marker. Each marker will be quantified automatically by digital image procedures using Image-Pro Plus and Image-J software. Associations of survival, relapse and other clinicopathological variables with the automatically quantified levels of immune infiltrates in patients with and without axillary node metastasis will be sought. ETHICS AND DISSEMINATION: The present project has been approved by the Clinical Research Ethics Committee of the Hospital Universitari Joan XXIII (Ref: 22p/2011). Those patients whose biopsies and clinical data are to be used will give their signed informed consent. Results will be published in peer-reviewed journals.

[Latent tuberculosis infection in healthcare personnel at a primary level general hospital in Catalonia, Spain]. / Infección tuberculosa latente en trabajadores sanitarios de un hospital general básico en Cataluña.

The aim was to analyze the prevalence of latent tuberculosis infection and associated risk factors in healthcare personnel at the Hospital de Tortosa Verge de la Cinta (Tarragona, Spain). This was a cross-sectional study of 398 workers at this hospital who underwent tuberculin skin testing for latent tuberculosis infection (LTBI) between 2001 and 2012.We also analyzed the relationship between LTBI and age, sex, job and work area according to their risk of exposure to tuberculosis(high, low, uncertain). The total prevalence of LTBI in our sample was 11.1% (95%CI 8.3%-14.5%). LBTI was associated with age and work area. Multivariate analysis showed that the risk of LTBI increased by 6.4% per 1 year increase in age. The prevalence of LTBI in this population approximates that of the general population in Spain.

El objetivo del trabajo ha sido evaluar la presencia de infección tuberculosa latente en el personal sanitario del Hospital de Tortosa Verge de la Cinta (HTVC). Para ello se analizaron las historias clínicas laborales de 398 trabajadores de dicho hospital a los que se había realizado la prueba de tuberculina durante el periodo 2001-2012. La presencia de infección tuberculosa latente (ITL) se analizó en relación a las variables edad, sexo, categoría profesional, personal de áreas de trabajo de alto y bajo riesgo de exposición a la tuberculosis y personal de riesgo no definido. La prevalencia total de ITL en el grupo estudiado fue del 11,1% (IC 95%: 8,3%-14,5%), estando dicha prevalencia asociada a la edad y al área de trabajo. El análisis multivariable mostró que el riesgo de sufrir ITL se incrementa un 6,4% por cada año de edad. La prevalencia de ITL en el centro de estudio era similar a la de la población profesionalmente no expuesta de España.

Diagnosed, identified, current and complete depression among patients attending primary care in southern Catalonia: different aspects of the same concept.

The aims of this study were to explore the prevalence and the conceptualizations of depression detected by the healthcare system, identified by the patient or classified/identified in the validated Goldberg's questionnaire in a community. We conducted a cross-sectional evaluation of 317 patients. The different types of depression diagnosed, identified, current or total were stratified by age and gender groups. The difference in the conceptualization of depression from the medical or ordinary people point of view indicate that depression care requires the understanding of the lifestyle, beliefs, attitudes, family and social networks of the people the physicians and nurses care for.

Validation of various adaptive threshold methods of segmentation applied to follicular lymphoma digital images stained with 3,3'-Diaminobenzidine&Haematoxylin.

The comparative study of the results of various segmentation methods for the digital images of the follicular lymphoma cancer tissue section is described in this paper. The sensitivity and specificity and some other parameters of the following adaptive threshold methods of segmentation: the Niblack method, the Sauvola method, the White method, the Bernsen method, the Yasuda method and the Palumbo method, are calculated. Methods are applied to three types of images constructed by extraction of the brown colour information from the artificial images synthesized based on counterpart experimentally captured images. This paper presents usefulness of the microscopic image synthesis method in evaluation as well as comparison of the image processing results. The results of thoughtful analysis of broad range of adaptive threshold methods applied to: (1) the blue channel of RGB, (2) the brown colour extracted by deconvolution and (3) the 'brown component' extracted from RGB allows to select some pairs: method and type of image for which this method is most efficient considering various criteria e.g. accuracy and precision in area detection or accuracy in number of objects detection and so on. The comparison shows that the White, the Bernsen and the Sauvola methods results are better than the results of the rest of the methods for all types of monochromatic images. All three methods segments the immunopositive nuclei with the mean accuracy of 0.9952, 0.9942 and 0.9944 respectively, when treated totally. However the best results are achieved for monochromatic image in which intensity shows brown colour map constructed by colour deconvolution algorithm. The specificity in the cases of the Bernsen and the White methods is 1 and sensitivities are: 0.74 for White and 0.91 for Bernsen methods while the Sauvola method achieves sensitivity value of 0.74 and the specificity value of 0.99. According to Bland-Altman plot the Sauvola method selected objects are segmented without undercutting the area for true positive objects but with extra false positive objects. The Sauvola and the Bernsen methods gives complementary results what will be exploited when the new method of virtual tissue slides segmentation be develop. VIRTUAL SLIDES: The virtual slides for this article can be found here: slide 1: http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=13617947952577 and slide 2: http://diagnosticpathology.slidepath.com/dih/webViewer.php?snapshotId=13617948230017.

Is it necessary to evaluate nuclei in HER2 FISH evaluation?

A new method that simplifies the evaluation of the traditional HER2 fluorescence in situ hybridization (FISH) evaluation in breast cancer was proposed. HER2 status was evaluated in digital images (DIs) captured from 423 invasive breast cancer stained sections. All centromeric/CEP17 and HER2 gene signals obtained from separated stacked DIs were manually counted on the screen. The global ratios were compared with the traditional FISH evaluation and the immunohistochemical status. The 2 FISH scores were convergent in 96.93% of cases, showing an "almost perfect" agreement with a weighted k of 0.956 (95% confidence interval, 0.928-0.985). The new method evaluates at least 3 times more nuclei than traditional methods and also has an almost perfect agreement with the immunohistochemical scores. The proposed enhanced method substantially improves HER2 FISH assessment in breast cancer biopsy specimens because the evaluation of HER2/CEP17 copy numbers is more representative, easier, and faster than the conventional method.