Cáncer de mama bilateral, ¿una sola enfermedad? Concordancia de receptores hormonales / Bilateral breast cancer, a single disease? Concordance of hormonal receptors

Introducción El incremento del diagnóstico de cáncer de mama en estadios tempranos conduce a un mejor pronóstico y, por ende, a una mayor expectativa de vida, situación que posibilitaría el desarrollo de un segundo tumor contralateral. Las mujeres con cáncer de mama tienen tres a cuatro veces mayor riesgo de desarrollar un cáncer en la mama contralateral. La patogénesis de la bilateralidad no está del todo clara; las correlaciones en el subtipo histológico, el grado tumoral y el estado de los Receptores Hormonales entre los dos tumores se han considerado indicativos de que se originan de una sola célula (teoría de origen monoclonal) con diseminación metastásica secundaria hacia la mama opuesta. Por otro lado, su discordancia llevaría a considerarla una lesión independiente del tumor primario (teoría de origen multiclonal). Dependiendo del tiempo de aparición entre un tumor y el otro, suelen ser de tipo sincrónico (cmbs) y metacrónico (cmbm). Objetivo Nuestro objetivo es describir las características clínico-patológicas y la concordancia de los Receptores Hormonales entre ambos tumores. Material y método Se llevó a cabo un estudio de corte transversal y retrospectivo en dos centros, el Hospital General de Agudos Dr. Ignacio Pirovano (hgaip) y Consultorio de práctica privada (pp) en el periodo comprendido entre el 1º de agosto de 2006 y el 1º de diciembre de 2014. Los datos fueron recabados de la base de datos del Registro de Cáncer de Mama (rcm) de la Sociedad Argentina de Mastología de ambas sedes. Resultados Identificamos 1.282 pacientes con cáncer de mama tratadas en hgadip (958) y pp (324) en dicho período. Encontramos 50 casos de cáncer de mama bilateral (3,9%), de los cuales 38 (2,96%) fueron de tipo metacrónico y 12 (0,94%) de tipo sincrónico. La edad media de presentación fue similar en ambos grupos (p=0,43): 52 años para el cmbm y 54 años para el cmbs. El 29% y el 41,6 % de las pacientes tenían antecedentes familiares de cáncer de mama en los cmbm y cmbs respectivamente (p=0,43). El primer tumor metacrónico fue palpable en el 71% de las pacientes y el segundo tumor metacrónico en el 7,9% (p<0,05). En cuanto a los sincrónicos, en todos los casos se presentaron como tumor palpable en una de las mamas y en un 58% como tumor no palpable en la mama contralateral. En el primer tumor metacrónico fue más utilizada la cuadrantectomía (44,7%) y el vaciamiento axilar (55,3 %); en cambio, en el segundo tumor metacrónico, se realizó la biopsia radioquirúrgica (60,5%) y el ganglio centinela (84,2%) (p<0,05). Para los sincrónicos, la cirugía más utilizada en el tumor dominante fue la mastectomía (41,7%) y la biopsia radioquirúrgica (33%) en el tumor contralateral; el ganglio centinela fue realizado en el 41,7% de las pacientes tanto en el tumor sincrónico dominante como en el contralateral. El tipo histológico predominante fue el carcinoma ductal invasor tipo nos: 57,9% en el primer tumor metacrónico, 65,8% en el segundo tumor metacrónico, 91,6% en el tumor sincrónico dominante y 41,6% en el tumor sincrónico contralateral. Se observó carcinoma ductal in situ (cdis) asociado: en el 36,8 % en el primer tumor metacrónico, en el 44,7% en el segundo tumor metacrónico, en el 25% en el tumor sincrónico dominante y en el 50% del sincrónico contralateral. El grado histológico (gh) predominante fue gh1 en el cmbm y gh3 en el cmbs. Los tratamientos adyuvantes más utilizados en el primer tumor metacrónico fueron la radioterapia en el 79%, la quimioterapia en el 68,4% y el tamoxifeno en el 60,5%; en el segundo tumor metacrónico el uso de la radioterapia fue casi similar (81,5%), disminuyó la utilización de quimioterapia adyuvante y de tamoxifeno, ambos a un 42,1%, y el uso de Inhibidores de Aromatasa se incrementó al 52,6%. El 58,3% de las pacientes con cmbs requirió radioterapia y el 75% quimioterapia adyuvante y tamoxifeno. El 86,8% de los primeros tumores metacrónicos fue positivo para re y rp, el 10,6% fue negativo para ambos y el 2,6% fue re positivo y rp negativo. En el segundo tumor metacrónico, el 92,1% fue positivo para re y rp, el 5,2% fue negativo para ambos y solo el 2,6% se presentó como re positivo y rp negativo. En el análisis de concordancia, se observaron 32 pares metacrónicos concordantes positivos para re, 2 pares metacrónicos discordantes positivo/negativo y 4 pares metacrónicos discordantes negativo/positivo. La relación fue similar para los re: 30 pares metacrónicos concordantes positivos, 3 pares metacrónicos discordantes positivo/negativo y 5 pares metacrónicos discordantes negativo/positivo. Se observó que el 58,4% de los tumores sincrónicos dominantes expresó re y rp positivos, y el resto (41,6%) fue negativo para ambos; en el tumor sincrónico contralateral, fue casi similar: el 66,7% de los casos expresó re y rp positivos y el 33,3% fue negativo para ambos. Se observaron 7 pares sincrónicos concordantes positivos para re y rp, 4 pares sincrónicos concordantes negativos para ambos y solo un par sincrónico discordante negativo/positivo. Conclusiones La gran mayoría de las pacientes fue diagnosticada con cáncer de mama bilateral como lesión subclínica en la mama contralateral por mamografía tanto en los metacrónicos como en los sincrónicos. No se ha demostrado que el riesgo disminuya a lo largo del tiempo, por lo que se destaca la importancia del seguimiento a largo plazo como pilar fundamental para la detección temprana del cbmm que probablemente tenga un impacto favorable en la supervivencia. La concordancia en la expresión de re y rp para el cmbm fue alta (79%) y para el cmbs fue aún mayor (92%), lo que podría reflejar un efecto del microambiente hormonal que influya tanto para la iniciación como para el desarrollo de estas lesiones de forma simultánea e independiente del origen único o multiclonal

Introduction The increase of the diagnosis in the early stages of breast cancer leads to a better prognosis and therefore a longer life expectancy, a situation that would allow the development of a second contralateral tumor. Women with breast cancer have three to four times greater risk of developing cancer in the contralateral breast. The pathogenesis of bilateral breast cancer is not entirely clear; correlations in the histologic subtype, tumor grade and Hormonal Receptor status between the two tumors have been considered as an indicative of single cell origin (Monoclonal origin theory) with secondary metastatic spread to the opposite breast; the discordance of those parameters would consider an independent lesion of the primary tumor (theory of multiclonal origin). They are named synchronous and metachronous depending on the time of onset. Objective Our study aims to describe the clinical-pathological characteristics and the concordance of the Hormonal Receptor status. Materials and method A cross-sectional and retrospective study was carried out at two centers, "Hospital General de Agudos Dr. Ignacio Pirovano" (hgaip) and private practice (pp) in the period from August 1, 2006 to January 1, December 2014. The data were collected from the database of "Registro de Cancer de Mama" (rcm) of the Argentine Society of Mastology (sam) from both centers. Results We identified 1,282 breast cancer patients treated in hgadip (958) and pp (324). We found 50 cases with bilateral breast cancer (cmb) (3.9%); 38 patients (2.96%) were metachronous and 12 patients (0.94%) synchronous. The mean age of presentation was similar in both groups (p = 0.43): 52 years old for cmbm and 54 in the cmbs group. The 29% and 41.6% of the patients had a breast cancer family history in the cmbm and cmbs respectively (p=0.43). The first metachronous tumor was clinically palpable in 71% of the patients and in the second one in 7.9% (p <0.05). In synchronous tumors, all cases were clinically palpable in one side of the breast and in 58% were subclinical in the contralateral side. In the first metachronous tumor, the quadrantectomy (44.7%) and the lymphadenectomy (55.3%) were more commonly used; on the other hand, in the second metachronuos tumor, the radio-surgical biopsy (60.5%) and sentinel lymph node (84.2%) were more executed (p <0.05). For the synchronous, the dominant tumor had more frequently a mastectomy (41.7%) and in the contralateral tumor the radio-surgical biopsy was executed in 33%; sentinel lymph node was performed in 41.7% in both synchronous tumors. The predominant histological type was the invasive ductal carcinoma nos type: 57.9% of the first metachronous tumor, 65.8% of the second metachronous tumor, 91.6% of the dominant synchronous tumor and 41.6% of the contralateral synchronic tumor. Ductal carcinoma in situ (dcis) was associated in 36.8% in the first metachronous tumor, 44.7% in the second metachronous tumor, 25% in the dominant synchronous tumor and 50% in the contralateral synchronic tumor. The predominant histological grade (gh) was gh1 in cmbm and gh3 in cmbs. The adjuvant treatments used for the first tumor were radiotherapy in 79%, chemotherapy in 68.4% and Tamoxifen in 60.5%. For the second metachronous tumor, the use of radiotherapy was almost similar with 81.58%, and the use of adjuvant chemotherapy and Tamoxifen decreased both at 42.11%; the use of Inhibitors of Aromatase increased to 52.6%.The 86.8% of the first metachronous tumors were er and pr positive, the 10.5% were both negative, the 2.6% were er positive and pr negative. In the second metachronous tumor, the 92.1% were er and pr positive, 5.2% were both negative and 2.6% were er positive and pr negative. In the concordance analysis, we observed 32 concordant metachronous pairs of er positive, 2 discordant metachronous pairs of positive / negative and 4 discordant metachronous pairs of negative / positive. We had similar results for pr, with 30 concordant metachronous positive pairs, 3 discordant metachronous pairs of positive / negative and 5 discordant metachronous pairs of negative / positive. The 58.4% of the dominant synchronous tumors expressed er and pr positive and in the rest (41.6%) were both negative. In the contralateral synchronous tumor it was observed that 66.7% of the cases expressed er and pr positive and 33.3% were negative for both. We found 7 concordant synchronous pairs of er and pr positive, 4 concordant synchronous pairs negative for both and only 1discordant synchronous pair negative / positive Conclusions In a big amount of the patients, the contralateral breast cancer was diagnosed as a subclinical lesion by mammography in the metachronous and synchronous tumors. It has not been demonstrated that the risk decreases over the time, which highlights the importance of long-term follow-up for early detection of cmbm that probably has more favorable impact on survival. The concordance of er and pr expression for cmbm was high (79%) and for cmbs was even higher (92%), that may reflect a particular hormonal environment effect that influences both initiation and development of these lesions simultaneously and independently of single or multiclonal origin

CXCR4/CXCL12 expression in the salivary gland and its significance in primary Sj?gren's syndrome / 中华风湿病学杂志

Objective To investigate the expression of CXCR4 and CXCL12 in the labial gland of patients with primary Sj?gren's syndrome (pSS), and to explore their role in the pathogenesis of pSS. Methods The expression of CXCR4 and CXCL12 in labial gland tissues was detected by immunohistochemistry in 32 cases of newly diagnosed pSS and 30 cases of oral mucosa cysts or trauma patients. The expression level, intensity and location were analyzed and compared statistically. χ2 test and Spearman correlation analysis were used for statistical analysis. Results The positive rate of CXCR4 in the test group was 91%(n=29), which was significantly higher than that in the control group (33%, n=10, χ2=21.77, P=0.001). The positive rate of CXCL12 in the test group was 97%(n=31), which was significantly higher than that in the control group 40%(n=12), and the difference was statistically significant ( χ2=23.57, P=0.001). Conclusion CXCR4 and CXCL12 are highly expressed in labial gland of pSS patients, this suggests that they participate in the pathological process of pSS local inflammatory response and play an important role in pSS pathogenesis.

Changes of Leptin and Janus Protein Tyrosine Kinase 2/Activating Transcriptor 3 Signal Transduction Pathways in Experimental Rats of Heart Failure With Cachexia / 中国循环杂志

Objective: To investigate the changes of serum levels of leptin in chronic heart failure (CHF) rats with cachexia and to study its mechanism via leptin receptor expression and leptin signal transduction pathways. Methods: There were 15/60 male SD rats were randomly used as Control group. CHF model was established in rest 45 rats by isoproterenol hydrochloride (ISO) injection as CHF group, n=36;9 rats died. According to body weight changes and echocardiography examination, CHF rats were further divided into 2 groups:cCHF group, the rats with cachexia, n=16 and ncCHF group, the rats with non-cachexia, n=20. Serum levels of leptin and protein levels of janus activating kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3) were examined by ELISA;the expressions of leptin receptor in the myocardial and adipose tissues were observed by immunohistochemistry;mRNA expressions of JAK2, STAT3 and SOCS3 in adipose tissue were detected by RT-PCR. Results: Serum levels of leptin, JAK2, STAT3 and the expressions of JAK2, STAT3 in adipose tissue were higher in both ncCHF and cCHF groups than Control group, P0.05. Serum levels of leptin, SOCS3 and mRNA expression of SOCS3 in cCHF group were lower than ncCHF group, P Conclusions: Increased serum level of leptin was involved in HF occurrence, leptin receptor expression and JAK2/STAT3 signal transduction pathways might be related to CHF combining cachexia in experimental rats.

Conceptos actuaees sobre mecanismos reguladores de la pubertad / Current concepts regarding mechanisms regulating puberty

El inicio de la pubertad depende de la activación del eje hipotálamo-hipofisiario-gonadal. Existe una red glial y neuronal que interactúa por medio de moléculas de adhesión, factores de crecimiento, aminoácidos, péptidos y derivados lipídicos, que permiten integrar en el hipotálamo la información del estado metabólico del individuo con la que proviene del medio ambiente determinando el comienzo y mantenimiento de la etapa reproductiva. En los últimos años se ha ampliado la comprensión de los factores que intervienen en la pubertad, aunque no se han dilucido todos los mecanismos participantes. Este artículo revisa algunos de los procesos celulares y moleculares más importantes en la regulación de la secreción pulsátil de GnRH, con mayor énfasis en los conocimientos más recientes.

The onset of puberty depends on activating the hypothalamic-pituitary-gonadal axis. A glial and neuronal network interacts by means of adhesion molecules, growth factors, amino acids, peptides and lipid derivates, leading to information about an individual's metabolic state becoming integrated with that from the environment in the hypothalamus and thereby determining the start of the reproductive stage and its maintenance. Understanding about the factors intervening in puberty has become greater during the last few years, even though all the participating mechanisms have not yet been elucidated. This article reviews some of the most important cellular and molecular processes in regulating pulsatile gonadotropin-releasing hormone (GnRH) secretion, placing greater emphasis on the most recent knowledge.

Expression of Y1 receptor during osteogenic differentiation of bone marrow mesenchymal stem cells / 中华创伤杂志

Objective To compare the expression changes of neuropeptide Y (NPY) receptor Y1 in different stages of osteoblast differentiation of rat bone marrow mesenchymal stem cells (BMSCs).Methods The rBMSCs were isolated in vitro from Sprague-Dawley (SD) rats using whole bone marrow adherence method and cultured. Then, the rBMSCs were divided into osteoblast-induced group and noninduced group. In different periods of culture at 1, 2 and 3 weeks, identification of the osteoblasts was performed by using immunocytochemistry and Western blot. Expressions of mRNA and protein of Y1 receptor were detected by real time reserve transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Results RT-PCR demonstrated that osteoblast-induced group had a lower expression of Y1 receptor than non-induced group at the same time point and the expression of Y1 receptor was increased in a time-dependent manner in both groups. Western blot demonstrated higher expression of Y1 receptor in osteoblast-induced group compared with non-induced group at the same time point and a decreased expression of Y1 receptor in a time-dependent manner in both groups. Conclusions During the process of osteoblastic differentiation of rat BMSCs, the expressions of mRNA and protein of NPY Y1 receptor show different trends, when NPY may mediate the inhibition of osteoblastic differentiation of BMSCs through Y1 receptor pathway.

Expression of tumor necrosis factor-related apoptosis-induce ligand receptors in bladder transitional cell cancer / 中华泌尿外科杂志

Objective To investigate the expression of tumor necrosis factor-related apoptosis-induce ligand (TRAIL) receptors in bla dder transitional cell cancer. Methods TRAIL receptors m RNA were tested by means of RT-PCR and Northern Blot in bladder transitional ce ll cancer tissue. Results The expression of death recept or 4 (DR4) and death receptor 5 (DR5) have been certificated in bladder transiti onal cell cancer and normal bladder tissue,decoy receptor 1 (DcR1) expressed onl y in normal bladder tissue. Conclusions TRAIL gene may p lay an important role in the apoptosis of bladder transitional cell cancer.

Expression of vitamin D receptor in rectal carcinoma and mucosa adjacent to carcinoma / 中国普通外科杂志

Objective To evaluate the expression of vitamin D receptor (VDR) in rectal cancer and mucosa adjacent to cancer. Methods The VDR expression of tumor tissue,mucos a 2cm apart from tumor and normal mucosa was detected by imunohistochemistry, mi crospectrophotometer and computer image analysis in 21 cases of rectal carcinoma . Results The VDR expression in rec tal tumor (2.4?0.7) significantly decreased compared to that of the norma l mucosa (6.0?0.6)(P

Expression of nerve growth factor and brain-derived neurotrophic factor in the dorsal root ganglion and the spinal dorsal horn following peripheral inflammatory hyperalgesia in rats / 中华麻醉学杂志

Objective To investigate the changes in the expression of nerve growth factor (NGF) and brain-derived neurotrophic (BDNF) in the dorsal root ganglion (DRG) and spinal dorsal horn following peripheral inflammatory hyperalgesia induced by formalin injected into the plantar region of the right hindpaw in rats. Methods Twenty-four adult SD rats weighing 250-400 g were studied. Peripheral inflammatory hyperalgesia was induced by an intraplantar injection of 5% formalin into right hindpaw. The animals were randomly divided into 4 groups (n=6 in each group), group A:control; group B:2 h after formalin injection; group C:24 h after formalin injection and group D: 48 h after formalin injection. Pain response was recorded. The expression of NGF and BDNF in the inflamed skin, DRG and spinal dorsal horn was detected using immuno-histochemistry technique and image analysis method. Results There were significant bi-phasic nociceptive responses induced by intraplantar injection of formalin in rats. The expression of NGF started to increase 2 h after injection, in the inflamed skin, ipsilateral DRG and dorsal horn neurons and reached the peak level at 24 h after injection. The expression of BDNF in ipsilateral DRG and dorsal horn neurons was unchanged 2 h after injection and started to increase at 24 h after injection. There was a positive correlateion between the expression of NGF and BDNF in ipsilateral DRG neurons.Conclusion NGF is not only an important transmitter in the peripheral mechanicsm of inflammatory pain but also involved in central sensitization through facilitating expression of BDNF in dorsal horn neurons.

Gene Mutation of RANTES and CCR5 in Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To evaluate the gene mutation of RANTES and CCR5 in SLE and its significance. Methods One hundred and forty-six definitive SLE patients and 159 controls were collected. SNPs of RANTES promoter and polymorphism of CCR5 were performed by PCR or PCR/RFLP assay, and further confirmed by direct DNA sequencing. Results The frequence of RANTES-403G/G compounded with 28C/C and CCR5/CCR5 was significantly different between SLE and control groups (72.6% vs 58.5%, P 0.05). Conclusions These results indicate that the two SNPs are linkage disequilibrium. Interaction of two SNPs in RANTES and CCR5 is related with SLE. RANTES-403G/G compounded with 28C/C and CCR5/CCR5 may be one of risk factors of SLE. RANTES-403A is probably related with renal damage of SLE.