Carbohydrate antigen 15-3 as a marker of disease severity in patients with chronic hypersensitivity pneumonitis* / Antígeno carboidrato 15-3 como marcador de gravidade da doença em pacientes com pneumonite de hipersensibilidade crônica

ABSTRACT Objective: Biomarkers associated with mucin 1, such as Krebs von den Lungen-6 and carbohydrate antigen (CA) 15-3, are increased in various interstitial lung diseases. Our aim was to determine whether CA 15-3 could be considered a biomarker of disease severity in patients with chronic hypersensitivity pneumonitis (cHP). Methods: This was a prospective observational study involving adult patients with cHP. Serum levels of CA 15-3 were measured and were correlated with variables related to disease severity and extension. HRCT scans were quantitatively analyzed using a computational platform and an image analysis tool (Computer Aided Lung Informatics for Pathology Evaluation and Rating). CA 15-3 levels were normalized by logarithmic transformation. Results: The sample comprised 41 patients. The mean age of the patients was 60.1 ± 11.6 years. The mean FVC in % of predicted was 70.3% ± 17.3%, and the median of the serum level of CA 15-3 was 48.1 U/mL. CA 15-3 levels inversely correlated with FVC in % of predicted (r = −0,30; p = 0,05), DLCO in % of predicted (r = −0,54; p < 0,01), and SpO2 at the end of a 4-min step test (r = −0,59; p < 0,01), but they directly correlated with total quantitative HRCT scores (r = 0,47; p = 0,004), especially regarding ground-glass opacities (r = 0.58; p < 0,001). Conclusions: CA 15-3 is likely to be a biomarker of disease severity of patients with cHP, particularly regarding gas exchange abnormalities.

RESUMO Objetivo: Biomarcadores associados à mucina-1, tais como Krebs von den Lungen-6 e carbohydrate antigen (CA, antígeno carboidrato) 15-3, encontram-se aumentados em diversas doenças pulmonares intersticiais. Nosso objetivo foi determinar se CA 15-3 poderia ser considerado um biomarcador de gravidade de doença em pacientes com pneumonite de hipersensibilidade crônica (PHc). Métodos: Estudo prospectivo observacional envolvendo pacientes adultos com PHc. Os níveis séricos de CA 15-3 foram medidos e correlacionados com variáveis relacionadas à gravidade e extensão da doença. As imagens de TCAR foram analisadas quantitativamente utilizando uma plataforma computacional e uma ferramenta de análise de imagem (Computer-Aided Lung Informatics for Pathology Evaluation and Rating). Os níveis de CA 15-3 foram normalizados por transformação logarítmica. Resultados: A amostra foi composta por 41 pacientes. A média de idade dos pacientes foi de 60,1 ± 11,6 anos. A média da CVF em % do previsto foi de 70,3% ± 17,3%, e a mediana do nível sérico de CA 15-3 foi de 48,1 U/mL. Os níveis de CA 15-3 se correlacionaram inversamente com CVF em % do previsto (r = −0,30; p = 0,05), DLCO em % do previsto (r = −0,54; p < 0,01) e SpO2 ao final de um teste de degrau de 4 minutos (r = −0,59; p < 0,01), mas se correlacionaram diretamente com a pontuação quantitativa total da TCAR (r = 0,47; p = 0,004), especialmente quanto a opacidades em vidro fosco (r = 0,58; p < 0,001). Conclusões: É provável que o CA 15-3 seja um biomarcador de gravidade de doença em pacientes com PHc, particularmente quanto a anormalidades nas trocas gasosas.

Dosagem sérica do marcador tumoral CA 15. 3 em cadelas portadoras de neoplasias mamárias pelo método de eletroquimioluminescência / Serum dosage of the tumor marker Ca 15. 3 in bitches presenting mammary neoplasia with the chemiluminescence method

The objective of the present study was to analyze the serum levels of the tumor marker Ca15.3 in healthy bitches and those with mammary neoplasms, correlating results with tumor type, clinical staging, time until presentation, and presence of ulceration and vascularization. For the study, 30 bitches with mammary tumors and 30 healthy bitches (control group) were selected. Histopathology was performed for identification of tumor type, and blood was collected for measurement of serum concentration of the marker via the chemiluminescence method using a commercial kit. A higher frequency of malignant neoplasms was observed (76.7%), with a higher quantity of carcinoma in mixed tumor (26.7%). Regarding serum concentration of the marker Ca15.3, there was no difference in serum values when comparing the means from bitches with neoplasia and healthy bitches, nor when comparing the other characteristics. The majority of results for serum concentration of Ca15.3, whether in bitches with neoplasia or in healthy bitches, was zero. It is concluded that the measurement of the marker Ca15.3 using the chemiluminescence method and commercial kits for humans did not offer significant results that would make this method or this marker a useful tool for patient monitoring and evaluation of the prognosis of bitches with mammary neoplasms.(AU)

Comparison of serum NEDD-9, CA 15-3, and CEA levels and PET metabolic parameters in breast cancer patients with 18 F-FDG PET / CT

SUMMARY OBJECTIVE Analyze the over expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) deregulated associated with a poor prognosis in various carcinomas. Our objective was to investigate the relationship between the levels of NEDD-9, CA 15-3, and CEA and PET (SUVmax, MTV40, TLG40) with the clinical parameters of patients with breast cancer (BC). METHODS One hundred and eleven patients (82 BC patients who underwent 18F-FDG PET/CT and 29 healthy controls) were evaluated. SUVmax, MTV, and TLG of the primary tumor were compared with the molecular and histopathological subtypes. 18F-FDG, MTV, and TLG were evaluated based on the clinical data, i.e., nodal involvement, distant metastasis, ER and PR status, Ki-67, serum levels of NEDD-9, CA15-3, and CEA. We compared the NEDD-9 in the BC and healthy control groups. RESULTS The mean ± SD of SUVmax in the 82 patients was 13.0 ± 8.6. A statistically significant relationship (p = 0.022) was found between the molecular subtypes and 18F-FDG uptake. The relationship between 18F-FDG uptake and TLG measured in patients <50 years, ER-PR negativity, and HER2 positivity were statistically significant (p=0.015, 0.007, 0.046, and 0.001, respectively). MTV40, TLG40, and CA 15-3 in metastatic patients were statistically significant (p=0.004, 0.005, and 0.003, respectively). NEDD-9 in the BC group was significantly higher than in the healthy group (p=0.017). There was a positive correlation between SUVmax and Ki67 and CA 15-3; MTV40 and CEA; CA 15-3, CEA, SUVmax, and MTV40; a negative correlation was found between CEA, TLG40, and age. CONCLUSION The use of SUVmax, MTV40, and TLG40 parameters with NEDD-9 and tumor markers has been shown to provide a high diagnostic, predictive, and prognostic value for the management of BC. This is considered to be the basis of interventions focused on the treatment objectives related to NEDD-9.

RESUMO OBJETIVO Analisar a associação da superrexpressão das células NEDD-9 ao prognóstico negativo em vários tipos de carcinoma. Nosso objetivo foi investigar a relação entre os níveis de NEDD-9, CA 15-3 e CEA e PET (SUVmax, MTV40, TLG) e os parâmetros clínicos em pacientes com câncer de mama (CM). MÉTODOS Cento e onze pacientes (82 pacientes de CM submetidos a 18F-FDG PET/TC e 29 controles saudáveis) foram avaliados. SUVmax, MTV, e TLG do tumor primário foram comparados nos subtipos molecular e histopatológico. A captação de 18F-FDG, MTV, e TLG foi avaliada com base em dados clínicos (envolvimento nodal, metástase distante, status de ER e PR, Ki-67, níveis séricos de NEDD-9, CA15-3 e CEA). Foi comparada a NEDD-9 do grupo de CM e o controle saudável. RESULTADOS A média ± DP de SUVmax de 82 pacientes foi de 13,0 ± 8,6. Uma relação estatisticamente significativa (p=0,022) foi encontrada entre subtipos moleculares e captação de 18F-FDG. A relação entre captação de 18F-FDG e TLG medida em pacientes com idade <50 anos, ER-PR negativo e HER2 positivo foi estatisticamente significativa (p=0,015; 0,007; 0,046; e 0,001, respectivamente). MTV40, TLG40 e CA 15-3 em pacientes metastáticos foram estatisticamente significantes (p=0,004, 0,005 e 0,003, respectivamente). NEDD-9 no grupo BC foi significativamente maior do que no grupo saudável (p=0,017). Uma correlação positiva foi encontrada entre SUVmax e Ki67 e CA 15-3; MTV40 e CEA; CA 15-3, CEA, SUVmax e MTV40; uma correlação negativa foi encontrada entre CEA, TLG40 e idade. CONCLUSÃO O uso dos parâmetros SUVmax, MTV40 e TLG40 com NEDD-9 e marcadores tumorais demonstrou um alto valor diagnóstico, preditivo e prognóstico para o manejo do CM. Isso é considerado a base para intervenções focadas nos objetivos de tratamento relacionados às NEDD9.

Expresión de Ki67 y MUC-1 en el adenocarcinoma no especificado de otra manera (NOS) de glándulas salivales: su valor pronóstico / Ki67 and MUC-1 expression in adenocarcinoma not otherwise specified (NOS) of salivary glands: prognostic value

El adenocarcinoma NOS (no especificado de otra manera) es un tumor salival sin patrón especial poco mencionado en la literatura; su diagnóstico es un desafío porque estructuralmente no se identifica con otros carcinomas salivales más definidos. Por otro lado, Ki67 es un marcador de proliferación celular que brinda información pronóstica de las neoplasias. En cuanto a la mucina humana transmembrana MUC-1 se sobre-expresa en las neoplasias malignas perdiendo su localización exclusivamente apical. Presentamos dos casos de adenocarcinoma NOS diagnosticados con H/E y correlacionamos la expresión de Ki67 y la localización y sobreexpresión de MUC-1 con su grado histológico y pronóstico. Cortes histológicos de dos adenocarcinomas NOS de parótida en mujeres de 62 y 63 años respectivamente se colorearon con H/E e inmunomarcaron para Ki67 y MUC-1. En ambos tumores predominaban estructuras ductales, algunas quísticas, cordones celulares ramificados e islotes sólidos. Las formaciones glandulares presentaban células claras y algunas de aspecto oncocítico. Había importante atipia celular, comedonecrosis, invasión perineural, áreas hemorrágicas y compromiso de los márgenes quirúrgicos. La marcación nuclear con Ki67 fue importante; MUC-1 presentó una fuerte coloración en membranas y citoplasmas. Las dos lesiones se diagnosticaron como de alto grado de malignidad. Nuestros resultados demuestran que existe una importante proliferación marcada con Ki67 y una sobre-expresión de MUC-1 asociadas a atipia celular, infiltración perineural, necrosis y compromiso de márgenes quirúrgicos, factores asociados a un peor pronóstico. El reconocimiento de este tumor es trascendente para médicos y odontólogos ya que por la ausencia de rasgos distintivos que sí presentan otros carcinomas más específicos es fundamental el diagnóstico de exclusión.

Adenocarcinoma NOS (not otherwise specified) is a no special pattern salivary tumor briefly mentioned in the literature; its diagnosis is a challenge because structurally it is not identified with other more definite salivary carcinomas. On the other hand, Ki67 is a marker of cellular proliferation that provides prognostic information of neoplasms. As for human transmembrane mucin, MUC-1 is overexpressed in malignant neoplasms, losing their exclusively apical location. We present two cases of adenocarcinoma NOS diagnosed with H/E and correlate the expression of Ki67 and the location and over-expression of MUC-1 with its histological grade and prognosis. Histological sections of two NOS adenocarcinomas of parotid in women of 62 and 63 ages respectively were stained with H/E and immunolabelled for Ki67 and MUC-1. Both are predominated by ductal structures, some cystic, branched cell cords and solid islets. The glandular formations presented clear cells and some of oncocytic appearance. There was important cellular atypia, comedonecrosis, perineural growth, haemorrhagic areas and compromise of surgical margins. Nuclear marking with Ki67 was important; MUC-1 presented a strong staining in membranes and cytoplasms. They were diagnosed as high-grade malignancy. Our results show that there is an important proliferation marked with Ki67 and overexpression of MUC-1 associated with cellular atypia, perineural growth, necrosis and compromise of surgical margins, factorsassociated with a poor prognosis. The recognition of this tumor is transcendent for physicians and dentists since, due to the absence of distinctive features that other more specific carcinomas present, the diagnosis of exclusion is essential.

Biomarcadores mamarios en procesos metastásicos en mujeres ecuatorianas / Breast biomarkers in metastatic processes in Ecuadorian women

Resumen Introducción: Los biomarcadores tumorales CA 15-3 y CEA son predictores de metástasis en el cáncer de mama; no obstante, existe división de criterios de las ventajas de determinarlos de forma individual o conjunta. Objetivo: Evaluar la asociación de los biomarcadores tumorales CA 15-3 y CEA, por separado y en conjunto, en relación a la enfermedad metastásica en mujeres ecuatorianas con cáncer de mama. Métodos: Se realizó un estudio de prevalencia, en base a la información obtenida de las historias clínicas de 90 mujeres con cáncer de mama. Se identificaron los marcadores (CA 15-3, CEA y el conjunto de los dos (CA 15-3 ­ CEA) y se buscó la asociación con presencia o no de metástasis mediante prueba exacta de Fisher e índice Kappa de Cohen. Además, se determinó la sensibilidad, especificidad y valores predictivos positivos y negativos de cada marcador tumoral y en conjunto. Resultados: La prevalencia de carcinoma ductal invasivo en etapas localmente avanzadas de IIB a IIIC fue 77.8%. El sistema óseo y pulmonar fueron lugares frecuentes de invasión. De manera individual y conjunta existe una relación estadísticamente significativa (P <0.05) entre el valor de los biomarcadores y la presencia de procesos metastásicos, siendo CA15-3 y CA15-3-CEA los de mayor concordancia. CA15-3 presentó sensibilidad (S) 55% y especificidad (E) 91%. CEA tuvo (S) 30%; (E) 96%. En conjunto presentaron (S) 40%; (E) 100%. Conclusiones: La presencia de metástasis y mayor carga tumoral se correlacionan con la positividad de los biomarcadores tumorales CA 15-3-CEA, lo cual refuerza la utilidad clínica de evaluar los dos biomarcadores en conjunto.

Background: CA 15-3 and CEA tumor markers are metastasis predictors in breast cancer; however, criteria of the advantages in determining them in an individual or joint way are still not consensual. Objective: To evaluate the association of CA 15-3 and CEA tumor markers, in individual or joint way, in Ecuadorian patients diagnosed with metastatic breast cancer. Methods: A prevalence study was carried out, based on the information obtained from the medical records of 90 women with breast cancer. The markers CA 15-3, CEA were identified individually and together (CA 15-3 - CEA) and the association between the presence or absence of metastasis was established by using Fisher's exact test and Cohen's Kappa index. In addition, the sensitivity, specificity, positive and negative predictive values of each tumor marker as individual element and as a whole were determined Results: The prevalence of invasive ductal carcinoma in locally advanced stages from IIB to IIIC was 77.8%. The bone and lung system were frequent sites of cancer spread. There was a statistically significant relation (p<0.05) between the individual or whole biomarkers values and the presence of metastatic processes, being CA 15-3 and CA 15-3-CEA the ones with the highest concordance. CA 15-3 presented 55% sensitivity and 91% specificity. CEA presented 30% sensitivity and 96% specificity. As a whole, those have 40% sensitivity and 100% specificity. Conclusions: A higher tumor burden and metastatic development correlate with CA15-3-CEA biomarker positivity as a set, reinforcing the clinical benefit of evaluating both biomarkers simultaneously

Avaliação comparativa de dosagem do marcador tumoral CA 15-3 em cadelas hígidas ou com neoplasia mamária / Comparative evaluation of tumor marker CA 15-3 dosage in dogs, healthy or with breast cancer

O antígeno CA 15-3 é uma proteína presente no soro utilizado no acompanhamento de mulheres com câncer de mama, essencialmente na detecção de metástases. Os objetivos deste estudo foram avaliar a efetividade e a viabilidade da utilização do marcador tumoral CA 15-3 em cadelas, comparando-se os valores do marcador entre cadelas sem e com neoplasia mamária, avaliando-se alterações nos valores do marcador após a mastectomia, e suas correlações entre o tipo histológico. Foi realizada a quantificação sérica do marcador tumoral CA 15-3 (teste de eletroquimioluminescência), em vinte cadelas hígidas (grupo controle) e vinte cadelas com neoplasia mamária (grupo teste). Os animais com neoplasia tiveram a dosagem do marcador realizada antes e 10 dias após a mastectomia. Ainda, foi realiza a citologia vaginal no momento da mastectomia e foram estabelecidos três grupos de acordo com a fase estral de cada cadela, Diestro, Proestro e Anestro. As massas tumorais foram encaminhadas para exame histopatológico. A avaliação dos dados de citologia vaginal entre os grupos Diestro, Proestro e Anestro pelo teste de ANOVA não demonstrou diferença estatística significativa entre os valores encontrados. E na análise para a comparação dos valores do marcador tumoral com os tipos histológicos de neoplasias, divididas em dois grupos, benignas e malignas, utilizando o teste de Mann-Whitney Rank Sum Test, o teste não demonstrou diferença estatística significativa visto que p>0,05. Os valores encontrados do marcador no grupo controle foram uma média de 0,19+0,39 U/mL, no grupo pré-mastectomia 1,56+0,39 U/mL e pós-mastectomia 0,66+0,27 U/mL. Em análise estatística com a comparação de grupo pré e pós-mastectomia, e do grupo controle com o grupo pré e pós-mastectomia observou-se significância com p< 0,005. Assim, observou-se diferença nos valores do marcador antes e depois da remoção cirúrgica da neoplasia, sugerindo seu possível uso como controle de crescimento tumoral pós-mastectomia individual. Porém há muita variação dos resultados nos diferentes métodos existentes, e não há ainda um padrão dos valores de referência para cada método, sendo necessários mais estudos sobre o uso dos marcadores.(AU)

The CA 15-3 antigen is a protein present in the serum, used to monitor women with breast cancer, mainly in metastatic disease detection. The objective of this study was to evaluate the effectiveness and feasibility of the CA 15-3 tumor marker in dogs, comparing the marker values between dogs with or without breast cancer, to estimate changes in marker values after mastectomy, and their correlation between the histological types. Serum quantification of the tumor marker CA 15-3 (electrochemiluminescence test) was performed in twenty healthy bitches and twenty others with mammary neoplasia. Bitches with cancer had the content of the tracer performed before and 10 days after mastectomy. The vaginal cytology was performed at the moment of the mastectomy, dividing the animals into three different groups (diestrus, proestrus and anestrus). All the mammary tumors were examined histopathologically. The evaluation of the vaginal cytology data of the groups Diestro, Proestro and Anestro by the ANOVA test did not show a statistically significant difference between the values ​​found. In the analysis histological types of tumor marker values of neoplasms, divided into two groups, benign and malignant, using the Mann-Whitney Rank Sum Test, there was no statistical significant difference at p>0.05. The values of the marker in the control group had an average of 0.19+0.39 U/mL, of the pre-mastectomy group 1.56+0.39 U/mL, and of the post-mastectomy group 0.66+0.27 U/mL. The statistic was performed comparing groups pre- and post-mastectomy, and the control group with group pre- and post-mastectomy with a statistical significance p< 0.005 in both tests. There was a difference of marker values ​​before and after surgical removal of the neoplasia, suggesting its possible use in post-mastectomy tumor control. But exist variation of results with the different existing methods, and there will be still a standard reference value for each method.(AU)

MUC-1 expression in pleomorphic adenomas using two human milk fat globule protein membrane antibodies (HMFG-1 and HMFG-2)

Pleomorphic adenoma (PA) is the most common salivary gland tumor and its microscopic features and histogenesis are a matter of debate. Human milk fat globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland tumors. Objective The aim of this study was to assess the immunoexpression of the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs, contrasting these results with those from normal salivary gland tissue. Material and Methods Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG-2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin method was used. Results Positivity to HMFG-1 and HMFG-2 MoAbs was found in ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls and intraductal mucous material. Two kinds of myoepithelial cells were identified: classic myoepithelial cells around ducts were negative to both MoAbs, and modified myoepithelial cells were positive to both MoAbs. This last cellular group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal epithelial cells using both HMFG antibodies. Intraductal mucous secretion was also HMFG-1 and HMFG-2 positive. Conclusions Our results showed there are two kinds of myoepithelial cells in PA. The first cellular group is represented by the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The second one is HMFG-negative and represented by the neoplastic myoepithelial cells located around the ducts. .

Lesiones gástricas en pacientes infectados con Helicobacter pylori: expresión de RAGE (receptor de productos de glicosilización avanzada) y otros inmunomarcadores / Expression of RAGE in Helicobacter pylori infested gastric biopsies

Background: Inflammation is a common phenomenon present in gastric mucosa of patients infected with H. pylori. Activation of the RAGE/multiligand axis is thought to be a relevant factor in cancer-mediated inflammation. RAGE is a membrane receptor, belonging to the immunoglobulin family, and the over-expression of RAGE has been associated with increased invasiveness and metastasis generation in different types of cancer, including gastric cancer. Furthermore recent experiences show that the use of its soluble form (sRAGE) or silencing of the gene coding for this receptor could provide therapeutic benefits in cancer. Aim: To evaluate the immunohistochemical expression of RAGE, MUC-1, β-Catenin free and phosphorylated, Cyclin-D1 and GSK3 in gastric biopsy specimens infected with H. pylori. Material and Methods: Immunohistochemical analysis was carried out in gastric biopsies from 138 patients: 55 with inflammatory injury (no atrophic gastritis), 42 with pre-cancerous conditions (atrophy or intestinal metaplasia) and 41 with dysplastic lesions or in situ adenocarcinoma. Results: There was a high rate of positive RAGE expression in the three groups of biopsies. Biopsies with dysplasia or in situ carcinoma had a significantly higher percentage of RAGE expression than the other groups of biopsies. Conclusions: The increased RAGE expression reported in both dysplasia and incipient cancer support the role of the multiligand/RAGE axis in gastric carcinogenesis.

Immunopathological features developing in the mosquito midgut after feeding on anopheles gambiae mucin-1 / interleukin-12 cDNA immunized mice / Desarrollo de características inmunopatológicas en el intestino medio del mosquito después de alimentarse de ratones inmunizados con mucina-1 / interleucina-12 ADNc de anopheles gambiae

The mosquito midgut is the organ into which the blood meal passes and in which, within a peritrophic membrane secreted by the epithelium, the blood is retained during digestion and absorption. The mosquito midgut is lined with an actin filled microvilli that are exposed to the harsh environment of the gut lumen such as food particle abrasion, digestive hydrolases and attack by pathogens and parasites that are taken in by the blood meal. These microvilli are protected them these effects by the peritrophic matrix, the glycocalyx and the mucin proteins that line their epithelial surfaces. Immunization of BALB/c mice with AgMUC1/IL-12 cDNA has been shown to kill mosquitoes when fed on these mice. Mucin is one of the proteins produced in the mosquito midgut after a blood meal. The fine structure of the mosquito midgut epithelium interacting with immune factors such as antibodies or immune cells is of special significance for interpreting early events in the interaction between the mosquito midgut lining and the specific immune components present in the blood of AgMUC1/IL-12 cDNA immunized BALB/c mice. Following bright light microscopy, scanning electron and transmission electron microscopic observations of the features seen in mosquito midgut sections from An. gambiae mosquitoes fed on BALB/c mice immunized with AgMUC1/IL-12 cDNA, the most likely immune mechanisms responsible for mosquito killing could be cell mediated, most likely antibody dependent cellular cytotoxicity. Both necrotic and apoptotic processes that could be the cause of mosquito death were seen to take place in the cells lining the midgut epithelium.

El intestino medio es el órgano al cual pasa la sangre consumida por el mosquito y donde, mediante una membrana peritrófica secretada por el epitelio, esta sangre es mantenida durante la digestión y absorción. El intestino del mosquito está revestido por microvellosidades llenas de actina que son expuestas a las complejas condiciones en torno a la luz intestinal, tales como la abrasión producida por partículas de alimentos, hidrolasas digestivas y el ataque de patógenos y parásitos que son tomados en la sangre consumida. Estas microvellosidades se protegen de estos efectos mediante la matriz peritrófica, el glicocálix y las proteínas de mucina que revisten las superficies epiteliales. La inmunización con AgMUC1/IL-12 ADNc en ratones BALB/c ha demostrado ser útil para matar los mosquitos cuando se alimentan de estos ratones. La mucina es una de las proteínas producidas en el intestino medio del mosquito después de consumir sangre. La fina estructura del epitelio del intestino interactúa con factores inmunes tales como anticuerpos o células inmunes es de especial importancia para interpretar los eventos tempranos en la interacción entre el revestimiento del intestino medio y los componentes inmunológicos específicos presentes en la sangre de ratones BALB/c inmunizados con AgMUC1/IL-12 cDNA. Después de observar mediante microscopías de luz, electrónica de barrido y de transmisión las características de secciones del intestino medio del mosquito Anopheles gambiae alimentado de ratones BALB/c inmunizados con AgMUC1/IL-12 cDNA, mecanismos inmunes mediados por citotoxicidad celular dependiente de anticuerpos (ADCC) podrían ser los responsables de matar a los mosquitos. Los procesos necróticos y apoptóticos que pueden ser la causa de la muerte del mosquito tienen lugar en las células que recubren el epitelio del intestino medio.

Hepatocyte antigen expression in subtypes of intestinal metaplasia of the stomach / Expresión del antígeno del hepatocito en los subtipos de metaplasia intestinal del estómago

OBJECTIVE: Recently, hepatocyte antigen (Hep) was introduced as a sensitive and reliable marker of intestinal metaplasia (IM). However, the distribution of Hep expression in subtypes of IM was not described. METHODS: We examined the expression of Hep in 58 cases of chronic gastritis associated with IM by immunohistochemical staining. Cases were classified as: 19 of IM Type I (complete) cases, 16 cases of IM Type II (incomplete) and 23 cases of IM Type III (incomplete). The distribution of Hep expression was classified into four groups according to the intensity of Hep expressing metaplastic cells: negative, low, moderate and high. We also compared expression of Hep with that of MUC-1, MUC-2 and MUC-5AC. RESULTS: Hep expression showed granular cytoplasmic staining and was specifically identified in columnar cells, but not in goblet cells. There was no significant difference between Hep expression and subtypes of IM (p > 0.005). However, the difference between the distribution of Hep expression among three subtypes of IM was significant (p < 0.001). No relationship was observed among the expression of Hep, MUC-1, MUC-2 and MUC-5AC. CONCLUSION: Results of the present study revealed that the distribution of Hep expression is high in the majority of the complete type (Type I) IM cases, moderate in the majority of the incomplete Type II IM cases and low in all of the incomplete Type III IM cases and suggest that besides its role as a sensitive marker in IM, the evaluation of the distribution of Hep expression might be useful in the classification of IM.

OBJETIVO: El antígeno del hepatocito (Hep) se introdujo recientemente como un marcador sensible y confiable de la metaplasia intestinal (MI). Sin embargo, no se describe la distribución de la expresión de Hep en los subtipos de MI. MÉTODOS: Se examinó la expresión de Hep en 58 casos de gastritis crónica asociados con MI mediante tinción inmunohistoquímica. Los casos fueron clasificados como: 19 casos de tipo MI (completo), 16 casos de tipo MI II (incompleto), y 23 casos de tipo MI III (incompleto). La distribución de la expresión del Hep se clasificó en cuatro grupos según la intensidad de Hep, que expresa las células metaplásticas: negativa, baja, moderada y alta. También se comparó la expresión de Hep con la de MUC-1, MUC-2 y MUC-5AC. RESULTADOS: La expresión de Hep mostró tinción citoplasmática granular, específicamente identificada en las células columnares, pero no en las células caliciformes. No hubo ninguna diferencia significativa entre la expresión de Hep y los subtipos de MI (p > 0.005). Sin embargo, la diferencia entre la distribución de la expresión del Hep entre tres subtipos de MI fue significativa (p < 0.001). No se observó relación alguna entre la expresión de Hep, MUC-1, MUC-2 y MUC-5AC. CONCLUSIÓN: Los resultados del presente estudio revelaron que la distribución de la expresión de Hep es alta en la mayoría de los casos MI de tipo completo (tipo I), moderada en la mayoría de los casos MI de tipo II, y baja en todos los casos MI de tipo III incompleto. Los resultados sugieren que además de su papel como marcador sensible en MI, la evaluación de la distribución de expresión del Hep podría ser útil en la clasificación de MI.

Metástasis óseas múltiples de cáncer de mama: papel del CA 15.3 y respuesta a la hormonoterapia / Bone metastasis of breast carcinoma: role of tumoral marker CA 15.3 and hormonal therapy response

Las metástasis óseas suponen el 65-75 por ciento de casos de cáncer de mama avanzado. Los marcadores tumorales (CA 15.3, CEA) son útiles en el seguimiento de las pacientes y en la valoración de la respuesta al tratamiento. En el cáncer de mama metastásico de bajo grado, el tratamiento hormonal es la opción terapéutica más acertada debido a la baja toxicidad y alta probabilidad de respuesta generalmente de larga duración a la que se asocia. Se presenta el caso de una paciente con cáncer de mama tratado con cirugía, quimioterapia y radioterapia, asintomática durante el seguimiento y en la que metástasis óseas múltiples son detectadas a partir de una elevación del marcador CA 15.3. La hormonoterapia es el tratamiento pautado inicialmente con buena respuesta y tolerancia. Dicho tratamiento logra estabilizar las lesiones óseas durante 7 años y es precisamente al suspenderlo cuando aparecen nuevas lesiones también a nivel óseo detectadas de nuevo ante un incremento del marcador CA 15.3. La terapia hormonal pautada de nuevo vuelve a conseguir estabilizar las lesiones.

Bone metastases are involved in a 65-75 percent of advanced metastatic breast cancer cases. Tumoral markers (CEA, CA 15.3) are useful in the follow-up and evaluation of response to treatment. Hormonal therapy is the optimal treatment option in low grade metastatic breast cancer due to low toxicity and general long term good response. We present a breast cancer case treated with surgery, chemotherapy and radiotherapy. The patient was asymptomatic during the follow-up and multiple bone metastases were diagnosed as a result of an increased CA 15.3 marker found. Hormone therapy was the recommended initial treatment with good response and tolerance. Bone lesions remained stabilized for 7 years but after treatment suspension new bone lesions appeared. CA 15.3 marker had increased again. Reintroduction of hormonal therapy achieved again the stabilization of the lesions.