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.

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.

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.

The tumour microenvironment as an integrated framework to understand cancer biology.

Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental. From this standpoint, different aspects of tumour lesions such as morphology, aggressiveness, prognosis and treatment response can be considered under an integrated vision, giving rise to a new field of study and clinical management. Nowadays, somatic mutation theory is complemented with study of TME components such as the extracellular matrix, immune compartment, stromal cells, metabolism and biophysical forces. In this review we examine recent studies in this area and complement them with our own research data to propose a classification of stromal changes. Exploring these avenues and gaining insight into malignant phenotype remodelling, could reveal better ways to characterize this disease and its potential treatment.

Amplification of Trichloroisocyanuric Acid (TCCA) Reactivity for Chlorination of Arenes and Heteroarenes via Catalytic Organic Dye Activation.

Heteroarenes and arenes that contain electron-withdrawing groups are chlorinated in good to excellent yields (scalable to gram scale) using trichloroisocyanuric acid (TCCA) and catalytic Brilliant Green (BG). Visible-light activation of BG serves to amplify the electrophilic nature of TCCA, providing a mild alternative approach to acid-promoted chlorination of deactivated (hetero)aromatic substrates. The utility of the TCCA/BG system is demonstrated through comparison to other chlorinating reagents and by the chlorination of pharmaceuticals including caffeine, lidocaine, and phenazone.

Desarrollo histórico de la especialidad de Alergología en Sancti Spíritus. 1978-2017 / Historical development of the specialty of Allergology in Sancti Spíritus. 1978-2017

Fundamento: En la provincia Sancti Spíritus se corroboró la inexistencia de documentos sobre la historia de la especialidad Alergología, por ello es necesario una investigación documental que pueda incidir en la formación de las generaciones actuales y futuras. Objetivo: Describir el desarrollo histórico de la especialidad de Alergología en la provincia Sancti Spíritus. Desarrollo: Se realizó una investigación cualitativa que se apoyó en los métodos teóricos, histórico lógico, análisis y síntesis, así como la entrevista y el análisis documental en el período comprendido entre 1978 y 2017 Conclusiones: La especialidad alcanzó un alto nivel de desarrollo y estabilidad en la asistencia, docencia e investigación, con Departamentos de Alergología con un especialista y enfermera entrenada en la atención primaria y secundaria lo que permitió brindar atención especializada de alta calidad al paciente alérgico y su familia, asimismo mantener la colaboración docente a otras provincias de la región central y del resto del país.

Background: The absence of documents on the history of the Allergology specialty in Sancti Spíritus province was confirmed, for this reason a documentary research is necessary which could influence in the formation of current and future generations. Objective: To describe the historical development of the specialty of Allergology in Sancti Spíritus province. Development: A qualitative research was carried out based on the theoretical methods, historical logic, analysis and synthesis, as well as the interview and the documentary analysis from 1978 to 2017 Conclusions: The specialty reached a high level of development and stability in care, teaching and research, having Departments of Allergology with a specialist and a nurse both trained in primary and secondary care which allowed providing high-quality specialized care to the allergic patient and his family, also maintaining the teaching collaboration to other provinces from the central region and the rest of the country.

Inmunoterapia con vacunas Valergen por vía sublingual en asmáticos de Cabaiguán, Sancti Spíritus / Immunotherapy with Valergen sublingual vaccines in asthmatics patients from Cabaiguan to Sancti Spiritus

Introducción: la inmunoterapia sublingual se abre paso en la práctica alergológica, numerosos estudios avalan su eficacia y seguridad. Objetivo: caracterizar los resultados con el uso de las vacunas Valergen vía sublingual, en pacientes asmáticos, del municipio Cabaiguán. Método: se realizó una investigación descriptiva-prospectiva, de enero del 2013 a diciembre del 2016 en pacientes con diagnóstico de asma bronquial intermitente, persistente leve y moderado. El universo quedó constituido por 467 pacientes. La muestra fue de 44 pacientes, de todas las edades y sexos que reunían esas condiciones, fueron atendidos en consulta durante todo el periodo de estudio y evaluado cada paciente al cumplir tres años de tratamiento con inmunoterapia. Los datos fueron obtenidos de las historias clínicas y del registro de vacunación del departamento de alergia. Resultados: predominaron los pacientes del sexo femenino, entre 5-14 años (34,1 por ciento), el Dermatofagoide pteronyssinus fue el ácaro de mayor sensibilidad y utilización (45,4 por ciento), a los 3 años de tratamiento predominaron los pacientes con un mejor control de sus síntomas (72,7 por ciento), no se presentaron eventos adversos (79,5 por ciento) en los pacientes, los presentados fueron clasificados como locales y/o sistémicos leves (20,5 por ciento). Conclusiones: la inmunoterapia sublingual para el asma bronquial demostró ser segura y clínicamente favorable en los pacientes estudiados(AU)

Introduction: sublingual immunotherapy makes its way into allergological practice and numerous studies confirm its effectiveness and safety. Objective: to characterize the results with the use of Valergen sublingual vaccines in asthmatic patients of Cabaiguan municipality. Method: a descriptive-prospective investigation was conducted from January 2013 to December 2016 in patients diagnosed with intermittent bronchial asthma, persistent, slow and moderate. The universe was constituted by 467 patients. The sample was of 44 patients, of all ages and sexes, who met these conditions, were seen in consultation during the studied period and evaluated each patient after three years of treatment with immunotherapy. The data were obtained from the clinical records and the vaccination record of the allergy department. Results: female patients between 5-14 years (34.1percent), and Dermatophagoide pteronyssinus was the mite with the highest sensitivity and use (45.4 percent), after 3 years of treatment, patients with a better control of their symptoms (72.7 percent), there were no adverse events (79.5percent) in the patients, those presented were classified as local and mild systemic (20.5 percent). Conclusions: sublingual immunotherapy for bronchial asthma proved to be safe and clinically favorable in the patients(AU)

Comportamiento de la sibilancia en niños menores de cinco años de la provincia Sancti Spíritus / Behavior of respiratory sounds in children less than five years of Sancti Spíritus

La sibilancia en niños preescolares se encuentra entre las principales causas de morbilidad atendida en las consultas de alergología y representa un importante número de ingresos hospitalarios. Objetivo: caracterizar el comportamiento de la sibilancia en niños menores de cinco años ingresados en el servicio de respiratorio del Hospital Pediátrico Docente Provincial José Martí Pérez de Sancti Spíritus, en el período noviembre de 2015 a noviembre de 2016. Método: se realizó un estudio descriptivo, transversal, el universo quedó constituido por 242 pacientes menores de cinco años ingresados por sibilancia en dicho servicio. Entre las variables que se estudiaron se encuentran: grupos de edad, sexo, antecedentes atópicos familiares, diagnóstico nosológico, fenotipo. Resultados: predominaron los lactantes, el sexo masculino, la residencia urbana, la bronquiolitis como diagnóstico al ingreso, el antecedente de atopia familiar fue más frecuente entre sus madres con diagnóstico de asma, los antecedentes atópico personal; la sibilancia persistente atópica tuvo mayor frecuencia; la inmunoglobulina E total estuvo elevada en un número frecuente de los casos. Conclusiones: el mayor número de casos en los pacientes incluidos tuvo riesgo de asma bronquial, con predominio de varones, historia familiar presente y personal de atopia, así como inmunoglobulina E sérica total elevada(AU)

Respiratory sounds in preschool children are the main causes of morbidity treated in allergy clinics and represent a significant number of hospital admissions. Objective: to characterize the behavior of wheezing in children less than five years admitted to the respiratory service of the Pediatric Teaching Provincial Hospital José Martí of Sancti Spíritus, from November 2015 to November 2016. Method: a study was descriptive, transversal; the universe was constituted by 242 patients less than five years admitted for wheezing in this service. Among the studied variables: age groups, sex, family atopic background, nosological diagnosis, and phenotype. Results: predominated infants, male sex, urban residence, bronchiolitis as diagnosis at admission, the history of family atopic was more frequent among mothers with a diagnosis of asthma, the personal atopic background; persistent atopic wheezing was more frequent; Total immunoglobulin E was elevated in a frequent number of cases. Conclusions: the highest number of cases in the included patients had a risk of bronchial asthma, with predominance of males, present family history and atopic family history as well as elevated total serum immunoglobulin E(AU)

Inmunoterapia con vacunas Valergen por vía sublingual en asmáticos de Cabaiguán, Sancti Spíritus / Imunoterapia com vacinas de Valerge por via sublingual em asmáticos de Cabaiguán, Sancti Spíritus / Immunotherapy with Valergen sublingual vaccines in asthmatics patients from Cabaiguan to Sancti Spiritus

Introducción: la inmunoterapia sublingual se abre paso en la práctica alergológica, numerosos estudios avalan su eficacia y seguridad. Objetivo: caracterizar los resultados con el uso de las vacunas Valergen vía sublingual, en pacientes asmáticos, del municipio Cabaiguán. Método: se realizó una investigación descriptiva-prospectiva, de enero del 2013 a diciembre del 2016 en pacientes con diagnóstico de asma bronquial intermitente, persistente leve y moderado. El universo quedó constituido por 467 pacientes. La muestra fue de 44 pacientes, de todas las edades y sexos que reunían esas condiciones, fueron atendidos en consulta durante todo el periodo de estudio y evaluado cada paciente al cumplir tres años de tratamiento con inmunoterapia. Los datos fueron obtenidos de las historias clínicas y del registro de vacunación del departamento de alergia. Resultados: predominaron los pacientes del sexo femenino, entre 5-14 años (34,1 por ciento), el Dermatofagoide pteronyssinus fue el ácaro de mayor sensibilidad y utilización (45,4 por ciento), a los 3 años de tratamiento predominaron los pacientes con un mejor control de sus síntomas (72,7 por ciento), no se presentaron eventos adversos (79,5 por ciento) en los pacientes, los presentados fueron clasificados como locales y/o sistémicos leves (20,5 por ciento). Conclusiones: la inmunoterapia sublingual para el asma bronquial demostró ser segura y clínicamente favorable en los pacientes estudiados(AU)

Introduction: sublingual immunotherapy makes its way into allergological practice and numerous studies confirm its effectiveness and safety. Objective: to characterize the results with the use of Valergen sublingual vaccines in asthmatic patients of Cabaiguan municipality. Method: a descriptive-prospective investigation was conducted from January 2013 to December 2016 in patients diagnosed with intermittent bronchial asthma, persistent, slow and moderate. The universe was constituted by 467 patients. The sample was of 44 patients, of all ages and sexes, who met these conditions, were seen in consultation during the studied period and evaluated each patient after three years of treatment with immunotherapy. The data were obtained from the clinical records and the vaccination record of the allergy department. Results: female patients between 5-14 years (34.1 percent), and Dermatophagoide pteronyssinus was the mite with the highest sensitivity and use (45.4 percent), after 3 years of treatment, patients with a better control of their symptoms (72.7 percent), there were no adverse events (79.5 percent) in the patients, those presented were classified as local and mild systemic (20.5 percent). Conclusions: sublingual immunotherapy for bronchial asthma proved to be safe and clinically favorable in the patients(AU)

Introdução: a imunoterapia sublingual faz parte da prática alergológica, e numerosos estudos confirmam sua eficácia e segurança. Objetivo: caracterizar os resultados com o uso de vacinas sublinguais de Valergen, em pacientes asmáticos, do município de Cabaiguán. Método: inquérito descritivo-prospectivo foi realizado no período de janeiro de 2013 a dezembro de 2016 em pacientes com diagnóstico de asma brônquica intermitente, persistente leve e moderada. O universo foi constituído por 467 pacientes. A amostra foi de 44 pacientes, de todas as idades e sexos que preencheram essas condições, foram atendidos em consulta durante todo o período do estudo e avaliaram cada paciente após três anos de tratamento com imunoterapia. Os dados foram obtidos a partir dos registros clínicos e do registro de vacinação do departamento de alergia. Resultados: predominaram pacientes do sexo feminino, entre 5-14 anos (34,1 por cento), Dermatophagoide pteronyssinus foi o ácaro com maior sensibilidade e utilização (45,4 por cento), após 3 anos de tratamento, pacientes com melhor controle de seus sintomas (72,7 por cento), não houve eventos adversos (79,5 por cento) nos pacientes, aqueles apresentados foram classificados como sistêmicos locais e / ou leves (20,5 por cento). Conclusões: a imunoterapia sublingual para asma brônquica mostrou-se segura e clinicamente favorável nos pacientes estudados(AU)

Comportamiento de la sibilancia en niños menores de cinco años de la provincia Sancti Spíritus / Behavior of respiratory sounds in children less than five years of Sancti Spíritus

Introducción: la sibilancia en niños preescolares se encuentra entre las principales causas de morbilidad atendida en las consultas de alergología y representa un importante número de ingresos hospitalarios. Objetivo: caracterizar el comportamiento de la sibilancia en niños menores de cinco años ingresados en el servicio de respiratorio del Hospital Pediátrico Docente Provincial "José Martí Pérez" de Sancti Spíritus, en el período noviembre de 2015 a noviembre de 2016. Método: se realizó un estudio descriptivo, transversal, el universo quedó constituido por 242 pacientes menores de cinco años ingresados por sibilancia en dicho servicio. Entre las variables que se estudiaron se encuentran: grupos de edad, sexo, antecedentes atópicos familiares, diagnóstico nosológico, fenotipo. Resultados: predominaron los lactantes, el sexo masculino, la residencia urbana, la bronquiolitis como diagnóstico al ingreso, el antecedente de atopia familiar fue más frecuente entre sus madres con diagnóstico de asma, los antecedentes atópico personal; la sibilancia persistente atópica tuvo mayor frecuencia; la inmunoglobulina E total estuvo elevada en un número frecuente de los casos. Conclusiones: el mayor número de casos en los pacientes incluidos tuvo riesgo de asma bronquial, con predominio de varones, historia familiar presente y personal de atopia, así como inmunoglobulina E sérica total elevada(AU)

Introduction: respiratory sounds in preschool children are the main causes of morbidity treated in allergy clinics and represent a significant number of hospital admissions. Objective: to characterize the behavior of wheezing in children less than five years admitted to the respiratory service of the Pediatric Teaching Provincial Hospital "José Martí" of Sancti Spíritus, from November 2015 to November 2016. Method: a study was descriptive, transversal; the universe was constituted by 242 patients less than five years admitted for wheezing in this service. Among the studied variables: age groups, sex, family atopic background, nosological diagnosis, and phenotype. Results: predominated infants, male sex, urban residence, bronchiolitis as diagnosis at admission, the history of family atopic was more frequent among mothers with a diagnosis of asthma, the personal atopic background; persistent atopic wheezing was more frequent; Total immunoglobulin E was elevated in a frequent number of cases. Conclusions: the highest number of cases in the included patients had a risk of bronchial asthma, with predominance of males, present family history and atopic family history as well as elevated total serum immunoglobulin E(AU)

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.

Biotensegrity of the extracellular matrix: physiology, dynamic mechanical balance, and implications in oncology and mechanotherapy.

Cells have the capacity to convert mechanical stimuli into chemical changes. This process is based on the tensegrity principle, a mechanism of tensional integrity. To date, this principle has been demonstrated to act in physiological processes such as mechanotransduction and mechanosensing at different scales (from cell sensing through integrins to molecular mechanical interventions or even localized massage). The process involves intra- and extracellular components, including the participation of extracellular matrix (ECM) and microtubules that act as compression structures, and actin filaments which act as tension structures. The nucleus itself has its own tensegrity system which is implicated in cell proliferation, differentiation, and apoptosis. Despite present advances, only the tip of the iceberg has so far been uncovered regarding the role of ECM compounds in influencing biotensegrity in pathological processes. Groups of cells, together with the surrounding ground substance, are subject to different and specific forces that certainly influence biological processes. In this paper, we review the current knowledge on the role of ECM elements in determining biotensegrity in malignant processes and describe their implication in therapeutic response, resistance to chemo- and radiotherapy, and subsequent tumor progression. Original data based on the study of neuroblastic tumors will be provided.

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.

Role of immune escape mechanisms in Hodgkin's lymphoma development and progression: a whole new world with therapeutic implications.

Hodgkin's lymphoma represents one of the most frequent lymphoproliferative syndromes, especially in young population. Although HL is considered one of the most curable tumors, a sizeable fraction of patients recur after successful upfront treatment or, less commonly, are primarily resistant. This work tries to summarize the data on clinical, histological, pathological, and biological factors in HL, with special emphasis on the improvement of prognosis and their impact on therapeutical strategies. The recent advances in our understanding of HL biology and immunology show that infiltrated immune cells and cytokines in the tumoral microenvironment may play different functions that seem tightly related with clinical outcomes. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of HL microenvironment. This new knowledge will probably translate into a change in the antineoplastic treatments in HL in the next future and hopefully will increase the curability rates of this disease.

Digital image analysis in breast cancer: an example of an automated methodology and the effects of image compression.

In the current practice of pathology, the evaluation of immunohistochemical (IHC) markers represents an essential tool. The manual quantification of these markers is still laborious and subjective, and the use of computerized systems for digital image (DI) analysis has not yet resolved the problems of nuclear aggregates (clusters). Furthermore, the volume of DI storage continues to be an important problem in computer-assisted pathology. In the present study we have developed an automated procedure to quantify IHC nuclear markers in DI with a high level of clusters. Furthermore the effects of JPEG compression in the image analysis were evaluated. The results indicated that there was an agreement with the results of both methods (automated vs. manual) in almost 90% of the analyzed images. On the other hand, automated count differences increase as the compression level increase, but only in images with a high number of stained nuclei (>nuclei/image) or with high area cluster (>25µm2). Some corrector factors were developed in order to correct this count differences. In conclusion, the proposed automated procedure is an objective, faster than manual counting and reproducible method that has more than 90% of similarity with manual count. Moreover, the results demonstrate that with correction factors, it is possible to carry out unbiased automated quantifications on IHC nuclear markers in compressed DIs.

Nonhepatosplenic γδ T-cell lymphomas represent a spectrum of aggressive cytotoxic T-cell lymphomas with a mainly extranodal presentation.

γδ T cells represent a minor T-cell subset that is mainly distributed in mucosal surfaces. Two distinct lymphomas derived from these cells have been recognized: hepatosplenic γδ T-cell lymphoma (HSTL) and primary cutaneous γδ T-cell lymphoma (PCGD-TCL). However, whether other anatomic sites may also be involved and whether they represent a spectrum of the same disease are not well studied. The lack of T-cell receptor (TCR)ß expression has been used to infer a γδ origin when other methods are not available. We studied 35 T-cell tumors suspected to be γδ TCL using monoclonal antibodies reactive with TCR δ or γ in paraffin sections. We were able to confirm γδ chain expression in 22 of 35 cases. We identified 8 PCGD-TCLs, 6 HSTLs, and 8 γδ TCLs without hepatosplenic or cutaneous involvement involving mainly extranodal sites. Two such cases were classified as enteropathy-associated T-cell lymphoma, type II. The other γδ TCL presented in the intestine, lung, tongue, orbit, and lymph node. In addition, we observed 13 cases with mainly extranodal involvement that lacked any TCR expression ("TCR silent"). In all cases, a natural killer cell origin was excluded. In conclusion, the lack of TCRß expression does not always predict γδ-T-cell derivation, as TCR silent cases may be found. The recognition of γδ TCL presenting in extranodal sites other than skin and liver/spleen expands the clinical spectrum of these tumors. However, non-HSTL γδ TCL do not seem to represent a single entity. The relationship of these tumors with either HSTL or PCGD-TCL requires further study.

Improved demonstration of immunohistochemical prognostic markers for survival in follicular lymphoma cells.

Follicular lymphoma (FL) is one of the most common forms of the low-grade non-Hodgkin's lymphoma in adults, with a characteristic translocation, t(14;18)(q32;q21) that deregulates the expression of the BCL2 gene. The clinical course of FL patients is variable, whereby a subset of patients survive for long periods even without relapses, whereas the majority have frequent relapses with shorter survival. We have analyzed a series of 186 FLs, studying the correlation between clinical outcome and the tumor cell expression of a set of immunohistochemical markers, using an automated procedure for tissue microarrays to reduce the subjectivity of scoring. The results identified several markers associated with differences in overall survival (OS) in univariate analyses, such as Cyclin E, Mdm2, CD10, p21, IgD, Bcl-xL, CD30, and E2F6. Cases with a higher level of expression of Cyclin E, Mdm2, p21, IgD, Bcl-xL, CD30, and E2F6 were associated with a significantly shorter OS. On the other hand, strong CD10 expression was linked to a significantly better outcome. A Cox model was then constructed, integrating the Follicular Lymphoma International Prognostic Index (FLIPI) score and a restricted selection of three immunohistochemical markers: Cyclin E, Mdm2, and CD10 expression. A potentially useful finding is that the integrated FLIPI plus immunohistochemical model can be used to identify a subset of 26 patients (almost 20% of the total series), with a survival probability of 100% at 5 years. This not only confirms that a group of FL cases may have a very good clinical course, but also indicates that this group can be identified using this integrated clinical and immunohistochemical approach.

Tumor microenvironment and immune effects of antineoplastic therapy in lymphoproliferative syndromes.

Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending on surrounding lymphoid infiltrates, lymphomas may have different prognosis. Moreover, recent evidences have emerged that confer a significant impact of main lymphoma's treatment over microenvironment, with clinical consequences. In this review, we summarize these concepts from a pathological and clinical perspective. Also, the state of the art of lymphoma's anti-idiotype vaccine development is revised, highlighting the situations where this strategy has proven to be successful and eventual clues to obtain better results in the future.

Morbilidad por Síndrome Metabólico en adultos mayores de cinco consultorios / Morbility by metabolic syndrome in elderly patients from five family doctors

La prevalencia actual del Síndrome Metabólico (SM) está aumentando en varios países de diferentes latitudes, convirtiéndose dichas regiones en un problema de salud relevante. De particular interés es la asociación del SM, con el riesgo elevado de mortalidad prematura por enfermedad de las arterias coronarias y cerebrovasculares en ambos sexos y con la incidencia de DM2 en adultos mayores.Objetivo de este trabajo fue caracterizar la morbilidad por Síndrome Metabólico en los adultos mayores, en consultorios seleccionados del Área de Salud Norte de la ciudad de Sancti-Spíritus. Se realizó una investigación descriptiva, observacional y transversal en una muestra probabilística de 116 adultos de 60 y más años de edad, para caracterizar el Síndrome Metabólico en cinco consultorios del área de salud Norte en la ciudad de Sancti-Spíritus, entre noviembre del 2007 y noviembre del 2008.Las variables estudiadas fueron morbilidad, los antecedentes personales y familiares de factores de riesgo y de enfermedades crónicas no trasmisibles, los datos fueron recogidos en un formulario, el análisis estadístico incluyó cálculo de porcentajes, estimación de parámetros y las pruebas de diferencia de proporciones (x2). La prevalencia de Síndrome Metabólico de 40,5 por ciento, principalmente del grupo clínico B (19,8 por ciento), su estratificación mostró predominio entre 65-69 años de edad (47,6 por ciento), sexo femenino (53,2 por ciento), los de piel blanca, con 95,7 por ciento y la escolaridad para la categoría baja (55,3 por ciento). Los antecedentes patológicos personales, para enfermedades crónicas no transmisibles registrados, fueron la hipertensión arterial, con 63,8 por ciento y la diabetes mellitus tipo 2, con 19,1 por ciento, en los antecedentes familiares fueron la cardiopatía isquémica y la enfermedad cerebrovascular, con igual comportamiento (57,4 por ciento) (AU)

Introduction: Nowadays the prevalence of metabolic síndrome (MS) has increased in many countries from different latitudes, becoming a health rpobelm in tose areas. It is particularly interesting the association of MS with the increased risk of premature death by disease of coronary arteries and cerebrovascular diseases, in both genders and with the incidence of DM2 in the elderly.Objectives: To characterize morbility by metabolic syndrome in the elderly in the doctor´s offices selected from the North Health area in the city of sancti Spiritus.Material and method: A descriptive observational and trasversal investigation was done in a probabilistic sample of 116 adults aged 60 or more to characterize the metabolic syndrome in five doctors offices from the north health area of Sancti spiritus city, between November 2007 and November 2008.The variables under study were morbility, sociodemographic, personal and familial antecedents with respect to risk factors and non- transmissible chronic diseases. The data were collected in a form and the statistics analysis included the calculation of percentages, the appraisal of parameters and the test of proportion differences (x2)(AU)Results: the prevalence of the metabolic syndrome of 40,5 por center, mainly in the clinical group B (19,8 por center). Its stratification showed the predominance of the age between 65- 69 years (47,6 por center), the female gender (53,2 por center), the wite race with 95,7 por center and the school level for a low category (55,3 por center).The pathologic antecedents for non- transmissible diseases were hypertension, with 63,8 por center and diabetes mellitus type 2 with 19,1por center. In the familial antecedents it was found out that both ischemic cardiopathies and cerebrovsacular disease had the same behaviour (57,4 por center)(AU)