Clasificación molecular del cáncer de mama: y su correlación clínica / Molecular classification of breast cancer: and this clinical correlation

La clasificación molecular del cáncer de mama ha definido grupos de riesgo y tratamientos diferentes, en este trabajo investigamos como se relacionaron estos grupos. Resultados de 320 pacientes vistas entre enero de 2007 y julio de 2009. En pacientes en las cuales se identifica un cáncer de mama en nuestra institución se realiza una evaluación inmunohistoquímica del tumor, con estos resultados se clasifican los tumores en cuatro subtipos: Luminal A y B, Her2neu y Basal Like. En la evaluación clínico-patológica se consideraron: método diagnóstico, edad, presentación clínica, tamaño del tumor, grado de diferenciación y tratamiento inicial. De 320 pacientes el tumor más frecuente fue Luminal A (60,63 por ciento), seguido por Basal Like (28,75 por ciento) Her2neu (9,06 por ciento) y Luminal B (1,56 por ciento). Los de peor pronóstico como los Basal Like y Her2neu, se consiguió mayor número de tumores palpables y menos diagnóstico subclínico por imágenes, mayor frecuencia en los grupos de menor edad, con mayor tamaño al examen físico y tumores más indiferenciados. Fue necesario iniciar tratamiento de quimioterapia de inducción como primera modalidad terapéutica en un 60,68 por ciento de los Basal Like y 62,06 por ciento de Her2neu, superior al 52,57 por ciento de los tumores Luminal A. La clasificación molecular permite identificar a los tumores con peor pronóstico. Las características histológicas también han identificado grupos de riesgo, pero con connotaciones terapéuticas muy generales. La clasificación molecular determina la posibilidad de suministrar tratamientos de quimioterapia más selectivos.

The molecular classification have defined risk groups and different treatments, the present study explores how these groups were related. 320 patients examinee between January 2007 and July 2009 all patients in which we identify breast cancer in our institution is conducting an assessment of immunohistochemistry according to these results are classified in four subtypes: Luminal A and B, Her2nNeu and Basal Like, also evaluating clinical-pathologic characteristic: Diagnostic method, age, clinical presentation, tumor size, degree of differentiation, initial treatment. In 320 patients the most frequent tumor was Luminal A with a 60.63 percent, followed by Basal Like (28.75 percent) Her2 Neu (9.06 percent) Luminal B (1.56 percent). In relation with worst prognosis of tumors were found more palpable tumors and less subclinical diagnostic by imaging, higher frequency in groups of younger women with larger tumors to physical examination and more undifferentiated. Tumors taking all these considerations needed to initiate treatment of induction chemotherapy as first therapeutic modality in 60.68 percent of the Basal and Like a Her2Neu of 62.06 percent, higher than 52.57 percent of the tumors more frequent Luminal A. The molecular classification of breast cancer let us identified tumors with worst prognosis. The histological features of the tumor have also identified risk groups, but with very broad therapeutic connotations, especially because it allows selection of treatments. On the other hand is only the molecular classification that determines the possibility to provide patients, selective chemotherapy treatments.

Rabbit antibodies for hormone receptors and HER2 evaluation in breast cancer / Anticorpos de coelho para avaliação de receptores hormonais e HER2 em câncer de mama

BACKGROUND: Novel rabbit monoclonal antibodies (RabMab) for estrogen (ER), progesterone (PR) receptors and HER2 evaluation by immunohistochemistry have recently been commercially released. We compared the RabMab anti-ER, anti-PR and anti-HER2 to mouse monoclonal antibodies (Mab) using tissue microarrays (TMA) of breast carcinomas. METHODS: Two TMA containing breast carcinomas were built. Sections were immunostained using anti-ER and anti-PR, Mab and RabMab. The sections stained for ER and PR were evaluated considering positive those tumors in which more than 1 percent of the tumor cell nuclei stained moderate or strong. For HER2, the immunostained sections were evaluated using the ASCO/CAP guidelines for HER2. Chromogenic in situ hybridization (CISH) was used as the gold standard for HER2 evaluation. CISH was evaluated using the Zymed HER2 CISH interpretation guidelines. RESULTS: RabMab against ER have similar staining patterns compared to the 6F11 (Mab), but stronger than 1D5 (Mab) from three different suppliers. The RabMab against PR provide stronger and sharper immunohistochemical signals compared to Mab. The detection of HER2 protein overexpression was more prevalent with the polyclonal antibodies and RabMab than with the Mab. These were more specific than the RabMab, which were more sensitive when compared to CISH. CONCLUSION: The novel RabMab against ER and PR showed higher intensity of staining than the Mab. The RabMab against HER2 is more sensitive than Mab, however, Mab presented more specificity than RabMab when compared to CISH for HER2 evaluation of breast carcinomas.

OBJETIVOS: Novos anticorpos monoclonais de coelho (RabMab) para a avaliação imuno-histoquímica de receptores de estrógeno (RE), progesterona (RP) e HER2 foram lançados comercialmente. Comparamos os RabMab anti-RE, anti-RP e anti-HER2 com os anticorpos monoclonais de camundongo (Mab) utilizando tissue microarrays (TMA) de carcinomas de mama. MÉTODOS: Foram construídos dois TMAs de carcinomas de mama. As secções foram marcadas usando anti-RE, anti-RP e anti-HER2, Mab e RabMab através de imuno-histoquímica. As secções marcadas para RE e RP foram avaliadas considerando positivos aqueles tumores nos quais mais de 1 por cento dos núcleos coraram moderadamente ou forte. Para HER2, as secções foram avaliadas utilizando as recomendações da ASCO/CAP para HER2. Hibridização in situ cromogênica (CISH) foi usada como padrão-ouro para avaliação de HER2. CISH foi avaliado utilizando as recomendações da Zymed. RESULTADOS: Os RabMab anti-RE apresentam intensidade de coloração semelhante ao 6F11 (Mab), porém maior que o 1D5 (Mab) proveniente de três diferentes fabricantes. Os RabMab anti-RP apresentaram sinal imunoistoquímico mais forte e delimitado comparado aos Mab. A detecção da superexpressão da proteína HER2 foi mais prevalente entre os anticorpos policlonais e RabMab, que se mostraram mais sensíveis quando comparados com o CISH. CONCLUSÃO: Os novos RabMab anti-RE e RP proporcionaram maior intensidade de coloração que os Mab. O RabMab anti-HER2 apresentou maior sensibilidade que os Mab, porém os Mab apresentaram maior especificidade quando comparados com o CISH para a avaliação de HER2 em carcinomas de mama.

Gender and sex hormones influence the response to trauma and sepsis: potential therapeutic approaches

Several clinical and experimental studies have demonstrated gender dimorphism in immune and organ responsiveness and in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses have been shown to be depressed in males following trauma-hemorrhage, whereas they were aintained/enhanced in proestrus females. Furthermore, sex hormones have been shown to be responsible for this gender-specific immune response following adverse circulatory conditions. More specifically, studies indicate that androgens produce immunodepression following trauma-hemorrhage in males. In contrast, female sex steroids appear to exhibit immunoprotective properties following trauma and severe blood loss. With regard to the underlying mechanisms, receptors for sex hormones have been identified on various immune cells suggesting direct effects of these hormones on the immune cells. Alternatively, indirect effects of sex hormones, ie, modulation of cardiovascular responses or androgen- and estrogen-synthesizing enzymes, might contribute to gender-specific immune responses. Recent studies indicate that sex hormones, eg, dehydroepiandrosterone (DHEA), also modulate the function of peripheral blood mononuclear cells in surgical patients. Thus, the immunomodulatory properties of sex hormones/receptor antagonists/sex steroid synthesizing enzymes following trauma-hemorrhage suggests novel therapeutic strategies for the treatment of immunodepression in surgical patients.

Uma série de estudos clínicos e experimentais demonstram a existência de dimorfismo sexual das respostas imunológicas e orgânicas, bem como da suscetibilidade e morbidade em relação ao choque, ao trauma e à sepse. Respostas imunes celularmente mediadas apresentam-se deprimidas em machos em resposta ao binômio trauma-hemorragia, mas conservados/enaltecidos em fêmeas em proestro. Adicionalmente demonstra-se que os hormônios sexuais são responsáveis por esta dicomotomia de resposta sexualmente específica, em condições cardiovasculares adversas. Estudos específicos indicam que os andrógenos produzem imunodepressão pós-trauma hemorragia em machos. Em contraste, esteróides sexuais femininos parecem exibir propriedades imunoprotetoras após episódios de trauma com ou sem perda importante de sangue. No terreno dos mecanismos subjacentes, foram identificados receptores para hormônios sexuais em várias células do sistema imunológico, sugerindo a existência de efeitos diretos destes hormônios sobre tais células. Alternativamente, observam efeitos indiretos de hormônios sexuais tais como modulação das respostas cardiovasculares das enzimas sintetizadores de andrógeno e estrógeno, que podem contribuir para as estas respostas sexualmente diferenciadas. Estudos recentes indicam que os hormônios sexuais, como por exemplo a dehidroepiandrosterona também modulam a função de células mononucleares da série branca em pacientes cirúrgicos. Assim, as propriedades imunomodulatórias de hormônios sexuais/antagonistas de receptores/enzimas sintetizadores de esteróides após a ocorrência de trauma ou de hemorragia sugerem o caminho para novas estratégias terapêuticas para o tratamento de imunodepressão em pacientes cirúrgicos.

Presencia de receptores de estrógeno, progesterona y CBG en el tracto genital de ovejas y perras: estudio inmmunocitoquímico comparativo / Presence of estrogen and progesterone receptors and CBG in the female tract of sheep and dogs: comparative immunochemistry study

Los receptores esteroidales sexuales del tracto genital de la hembra tienen importancia ya que a través de ellos actúan las hormonas responsables de su desarrollo y de sus cambios morfofuncionales. Dado que en su mecanismo de control uno de los factores a tenerse en cuenta son las posibles diferencias entre las distintas especies, los objetivos de nuestro estudio fueron comparar en dos especies distintas la ovina (O) (n=6) y la canina (P) (n=6) la presencia de receptores de estrógenos (RE), progesterona (RP) y de CBG en ovario, tuba uterina y útero de hembras prepúberes (O:n=3; P:n=·3) y adultas (O:n=3; P:n=3). Se realizaron tinción con H-E e inmunocitoquimica según técnica de Stenberger. Los resultados revelaron: en ambas especies en animales durante el ciclo estral inmunorreactividad (IR) positiva marcada para estrógenos en útero, oviducto y ovario siendo comparativamente los RE más numerosos en oviducto de perra que en oveja. En ambos animales en anestro, la IR para RE fue negativa o leve en útero, no evidenciándose su presencia en otros órganos. Los RP variaron según el estadio del ciclo, no mostrando diferencias destacables entre las especies. En las hembras prepúberes de oveja fueron detectados RE Y RP, mientras que en perras éstos no fueron evidenciados. La CBG mostró IR positiva en el tracto de ambos animales durante el ciclo y fue negativa en prepúberes para ambas especies. Se concluye que existen diferencias, especialmente en hembras prepúberes, donde la presencia de RE y RP es detectable en ovejas no así en perras, siendo además, la presencia de RE comparativamente más marcada en tuba uterina de perra en ciclo que en oveja en el mismo estadio.

The sexual steroid receptors of the genital tract of the female has importance since on them the hormones responsible for their development and morphofuncional changes act. Due that in their control mechanism one of the factors to be kept in mind is the possible differences among the diverse species. The objective of our study was to compare in two different species sheep (O) ( n=6) and canine (P) ( n=6) the presence of receptors of estrogens (RE), progesterone (RP) and the presence of CBG in ovary, oviduct and uterus of female prepúberes (O:n=3; Pn=·3) and mature: (O:n=3; Pn=·3) We use H-E tint and and inmunocito chemistry according to technique of Stenberger. The results revealed: in both species of animals during the estral cycle: Inmunorreactivity (RI) positive marked for estrogens in uterus, oviduct and ovary being comparatively much more numerous RE in dog oviduct that in sheep. In both animals in anestro RE was negative or light in uterus, without evidenced of their presence in other organs. The RP varied according to the stage of the cycle not showing remarkables differences among the species. In the prepuber female sheep RE and RP were detected while in dogs they were not evidenced. The CBG showed positivity in the tract of both animals during the cycle and it was negative in both prepuber species We concludes that differences exist especially in prepuber female where the presence of RE and RP are detectable in sheep and no detectable in dogs, being further the comparatively presence of RE in dog oviduct in cycle more marked that in sheep in the same stage.

Cáncer de la vesícula biliar: expresión inmunohistoquímica de la proteína relacionada con receptor estrogénico (p29) y de la proteína inducida por estrógeno (pS2) / Cáncer of gallbladder: immunohistochemical expression of estrogen receptor related protein (p29) and estrogen induced protein (pS2)

The high frequency of gallblader cancer in women suggest a role for estrogens in its development. The aim of this study was to study the immunohistochemical expression in of p29 estrogen receptor associated protein and pS2 estrogen induced protein in 111 pathological samples of gallbladder carcinoma, coming from 88 women and 23 men, 30 metastases of gallbladder cancer, coming from 25 women and 5 men and in 25 non-tumoral gallbladders. In the latter, p29 protein was positive in 12 samples (48 percent) and pS2 in 15 cases (60 percent). p29 was positive in 40 percent and pS2 in 32 percent of tumors. p29 expressed with higher frequency in metastases than in primary tumors (57 and 31 percent respectively, p<0.02). Early tumors had a significantly lower expression of p29 than advanced tumors or than metastases. Both proteins expressed in 18 percent of samples (synchronic expression) whereas one of both proteins did so in 60 percent of cases (asynchronic expression). We conclude that most gallbladder cancer samples express proteins associated to estrogen receptor or induced by estrogens