RESUMEN
Calcium pyrophosphate dihydrate deposition (CPDD) is the accepted name for a disease that mainly occurs in elderly patients. This disease affects many joints in particular the knee joint. CPDD is extremely rare in the temporomandibular joint (TMJ) with only few cases reported in the English literature. Herein, we present a case of an 89 years old woman with a radiological diagnosis of chondrosarcoma of TMJ. Fine-needle aspiration cytology however showed crystals, multinucleated giant cells and macrophages which allowed a correct diagnosis of CPDD.
Asunto(s)
Condrocalcinosis/patología , Articulación Temporomandibular/patología , Anciano de 80 o más Años , Biopsia con Aguja Fina , Femenino , HumanosRESUMEN
BACKGROUND: This study aimed to identify biomarkers for estimating the overall and prostate cancer (PCa)-specific survival in PCa patients at diagnosis. METHODS: To explore the importance of embryonic stem cell (ESC) gene signatures, we identified 641 ESC gene predictors (ESCGPs) using published microarray data sets. ESCGPs were selected in a stepwise manner, and were combined with reported genes. Selected genes were analyzed by multiplex quantitative polymerase chain reaction using prostate fine-needle aspiration samples taken at diagnosis from a Swedish cohort of 189 PCa patients diagnosed between 1986 and 2001. Of these patients, there was overall and PCa-specific survival data available for 97.9%, and 77.9% were primarily treated by hormone therapy only. Univariate and multivariate Cox proportional hazard ratios and Kaplan-Meier plots were used for the survival analysis, and a k-nearest neighbor (kNN) algorithm for estimating overall survival. RESULTS: An expression signature of VGLL3, IGFBP3 and F3 was shown sufficient to categorize the patients into high-, intermediate- and low-risk subtypes. The median overall survival times of the subtypes were 3.23, 4.00 and 9.85 years, respectively. The difference corresponded to hazard ratios of 5.86 (95% confidence interval (CI): 2.91-11.78, P<0.001) for the high-risk subtype and 3.45 (95% CI: 1.79-6.66, P<0.001) for the intermediate-risk compared with the low-risk subtype. The kNN models that included the gene expression signature outperformed the one designed on clinical parameters alone. CONCLUSIONS: The expression signature can potentially be used to estimate overall survival time. When validated in future studies, it could be integrated in the routine clinical diagnostic and prognostic procedure of PCa for an optimal treatment decision based on the estimated survival benefit.
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Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/mortalidad , Transcriptoma , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Análisis por Conglomerados , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: The oestrogen receptor (ER) co-activator amplified in breast cancer 1 (AIB1) has been suggested as a treatment predictive and prognostic marker in breast cancer. Studies have however not been unanimous. PATIENTS AND METHODS: AIB1 protein expression was analysed by immunohistochemistry on tissue micro-arrays with tumour samples from 910 postmenopausal women randomised to tamoxifen treatment or no adjuvant treatment. Associations between AIB1 expression, clinical outcome in the two arms and other clinicopathological variables were examined. RESULTS: In patients with ER-positive breast cancer expressing low tumour levels of AIB1 (<75%), we found no significant difference in recurrence-free survival (RFS) or breast cancer-specific survival (BCS) between tamoxifen treated and untreated patients. In patients with high AIB1 expression (>75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26-0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21-0.69, P = 0.0015) with tamoxifen treatment. In the untreated arm, we found high expression of AIB1 to be significantly associated with lower RFS (HR 1.74, 95% CI 1.20-2.53, P = 0.0038). CONCLUSION: Our results suggest that high AIB1 is a predictive marker of good response to tamoxifen treatment in postmenopausal women and a prognostic marker of decreased RFS in systemically untreated patients.
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Neoplasias de la Mama/tratamiento farmacológico , Coactivador 3 de Receptor Nuclear/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Tamoxifeno/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Posmenopausia , Resultado del TratamientoRESUMEN
STUDY QUESTION: What are the diagnostic benefits of using ultrasound in patients with a clinical suspicion of acute salpingitis and signs of pelvic inflammatory disease (PID)? SUMMARY ANSWER: In patients with a clinical suspicion of acute salpingitis, the absence of bilateral adnexal masses at ultrasound decreases the odds of mild-to-severe acute salpingitis about five times, while the presence of bilateral adnexal masses increases the odds about five times. WHAT IS KNOWN ALREADY: PID is difficult to diagnose because the symptoms are often subtle and mild. The diagnosis is usually based on clinical findings, and these are unspecific. The sensitivity and specificity of ultrasound with regard to salpingitis have been reported in one study (n = 30) of appropriate design, where most patients had severe salpingitis (i.e. pyosalpinx) or tubo-ovarian abscess. STUDY DESIGN, SIZE, DURATION: This diagnostic test study included 52 patients fulfilling the clinical criteria of PID. Patients were recruited between October 1999 and August 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients underwent a standardized transvaginal gray scale and Doppler ultrasound examination by one experienced sonologist (index test) before diagnostic laparoscopy by a laparoscopist blinded to the ultrasound results. The final diagnosis was determined by laparoscopy, histology of the endometrium and other histology where relevant (reference standard). MAIN RESULTS AND THE ROLE OF CHANCE: Of the 52 patients, 23 (44%) had a final diagnosis unrelated to genital infection, while the other 29 had cervicitis (n = 3), endometritis (n = 9) or salpingitis (n = 17; mild n = 4, moderate n = 8, severe, i.e. pyosalpinx n = 5). Bilateral adnexal masses and bilateral masses lying adjacent to the ovary were seen more often on ultrasound in patients with salpingitis than with other diagnoses (bilateral adnexal masses: 82 versus 17%, i.e. 14/17 versus 6/35, P = 0.000, positive likelihood ratio 4.8, negative likelihood ratio 0.22; bilateral masses adjacent to ovary: 65 versus 17%, i.e.11/17 versus 6/35, P = 0.001, positive likelihood ratio 3.8, negative likelihood ratio 0.42). In cases of salpingitis, the masses lying adjacent to the ovaries were on average 2-3 cm in diameter, solid (n = 14), unilocular cystic (n = 4), multilocular cystic (n = 3) or multilocular solid (n = 1), with thick walls and well vascularized at colour Doppler. In no case were the cogwheel sign or incomplete septae seen. All 13 cases of moderate or severe salpingitis were diagnosed with ultrasound (detection rate 100%, 95% confidence interval 78-100%) compared with 1 of 4 cases of mild salpingitis. Three of six cases of appendicitis, and two of two ovarian cysts were correctly diagnosed with ultrasound, and one case of adnexal torsion was suspected and then verified at laparoscopy. LIMITATIONS, REASONS FOR CAUTION: The sample size is small. This is explained by difficulties with patient recruitment. There are few cases of mild salpingitis, which means that we cannot estimate with any precision the ability of ultrasound to detect very early salpingitis. The proportion of cases with salpingitis of different grade affects the sensitivity and specificity of ultrasound, and the sensitivity and specificity that we report here are applicable only to patient populations similar to ours. WIDER IMPLICATIONS OF THE FINDINGS: The information provided by transvaginal ultrasound is likely to be of help when deciding whether or not to proceed with diagnostic laparoscopy in patients with symptoms and signs suggesting PID and, if laparoscopy is not performed, to select treatment and plan follow-up.
Asunto(s)
Salpingitis/diagnóstico por imagen , Enfermedad Aguda , Femenino , Humanos , Enfermedad Inflamatoria Pélvica/diagnóstico por imagen , Estudios Prospectivos , UltrasonografíaRESUMEN
Immunocytology is today accepted as an indispensable adjunct to cytomorphology. It has led to a dramatic increase in diagnostic accuracy and also allowed the identification of markers both for prognosis and targeted therapies. Most commercially available antibodies will perform in a reproducible and reliable way provided that the cytological specimen has been prepared and fixed properly. In this review various aspects of immunocytochemistry such as preparation of cytological specimens, fixation and choice of antibodies will be discussed. The specificity of the most commonly used antibodies is summarized and staining panels for various tumours are suggested. In addition, the use of markers for targeted therapy and theranostics is discussed, as well as a brief section on the identification of infectious agents.
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Biomarcadores de Tumor/análisis , Inmunohistoquímica/métodos , Neoplasias/patología , Anticuerpos/química , Anticuerpos/inmunología , Biomarcadores de Tumor/química , Epítopos/inmunología , Humanos , Estándares de Referencia , Manejo de Especímenes , Coloración y Etiquetado , Fijación del TejidoRESUMEN
BACKGROUND: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. METHODS: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomised prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modelling. RESULTS: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorised as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorised as low risk with an 8.3% 10-year distant recurrence risk. CONCLUSION: Retrospective analysis of this randomised, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.
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Neoplasias de la Mama/diagnóstico , Proteínas de Homeodominio/análisis , Receptores de Interleucina/análisis , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Detección Precoz del Cáncer , Femenino , Humanos , Metástasis de la Neoplasia , Neoplasias Hormono-Dependientes/diagnóstico , Posmenopausia , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Interleucina-17 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Suecia , Tamoxifeno/uso terapéuticoRESUMEN
BACKGROUND: Triple-negative breast cancer (TNBC) lacking expression of steroid receptors and human epidermal growth factor receptor 2, having chemotherapy as the only therapeutic option, is characterised by early relapses and poor outcome. We investigated intratumoural (i.t.) levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF) and survival in patients with TNBC compared with non-TNBC. PATIENTS AND METHODS: VEGF levels were determined by an enzyme immunosorbent assay in a retrospective series consisting of 679 consecutive primary breast cancer patients. RESULTS: Eighty-seven patients (13%) were classified as TNBC and had significantly higher VEGF levels; median value in TNBC was 8.2 pg/microg DNA compared with 2.7 pg/microg DNA in non-TNBC (P < 0.001). Patients with TNBC had statistically significant shorter recurrence-free survival [hazard ratio (HR) = 1.8; P = 0.0023], breast cancer-corrected survival (HR = 2.2; P = 0.004) and overall survival (HR = 1.8; P = 0.005) compared with non-TNBC. Patients with TNBC relapsed earlier than non-TNBC; mean time from diagnosis to first relapse was 18.8 and 30.7 months, respectively. The time between first relapse and death was also shorter in TNBC: 7.5 months versus 17.5 months in non-TNBC (P = 0.087). CONCLUSIONS: Our results show that TNBC have higher i.t. VEGF levels compared with non-TNBC. Ongoing clinical trials will answer if therapy directed towards angiogenesis may be an alternative way to improve outcome in this poor prognosis group.
Asunto(s)
Neoplasias de la Mama/genética , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neovascularización Patológica/genética , Receptor ErbB-2/análisis , Receptor ErbB-2/genética , Receptores de Estrógenos/análisis , Receptores de Estrógenos/genética , Receptores de Progesterona/análisis , Receptores de Progesterona/genética , Análisis de Supervivencia , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/análisis , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: To investigate the possible correlation between expression of HER2 and vascular endothelial growth factor (VEGF), and to determine the predictive value of these factors in patients receiving adjuvant endocrine therapy including the group with a breast cancer (BC) positive for both oestrogen receptor (ER) and progesterone receptor (PgR). MATERIAL AND METHODS: By enzyme immuno-sorbent assays (ELISA) tumour levels of HER2 and VEGF proteins were determined in 679 consecutive primary BC patients, median age 63 years, median follow-up time 92 months. A total of 404 patients received adjuvant endocrine therapy, mainly tamoxifen, out of them 295 had an ER and PgR positive BC. In 160 patients, HER2 status was also determined by immunohistochemistry (IHC) using the monoclonal antibody CB11. RESULTS: Overexpression of HER2 by IHC was found in 15% of the patients. Overexpression of HER2 by ELISA correlated with HER2 by IHC (P < 0.001) and a higher VEGF expression (P = 0.004). Patients receiving adjuvant endocrine therapy with high VEGF (RFS P = 0.0087, BCCS P = 0.0012) or over-expressing HER2 (RFS P = 0.0116, BCCS P = 0.0036) had significantly shorter survival. Factors retaining statistical significance in multivariate analyses for recurrence-free survival (RFS) were nodal status (P < 0.001), tumour size (P = 0.005) and VEGF (P = 0.032) and for breast cancer corrected survival (BCCS) nodal status (P < 0.001), tumour size (P = 0.001), ER status (P = 0.022), and VEGF (P = 0.016). Both factors were significantly correlated with survival in the group with a BC positive for both ER and PgR; VEGF (RFS P = 0.0177, BCCS P = 0.0321) and HER2 (RFS P = 0.0143, BCCS P = 0.0311). In multivariate analyses, nodal status (P < 0.001) and VEGF (P = 0.021) were independent factors for RFS. Nodal status (P < 0.001) and tumour size (P = 0.016) retained independent factors for BCCS. Combined analysis identified a high-risk group (HER2 positive and high VEGF) with significantly reduced survival. CONCLUSION: The results from this retrospective analysis suggest that overexpression of HER2 and higher VEGF expression may add information on patient's outcome after adjuvant endocrine therapy in ER and PgR positive BC.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidad , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Ensayo de Inmunoadsorción Enzimática , Femenino , Goserelina/uso terapéutico , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Tasa de Supervivencia , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Progestins as well as estrogens have a role in breast cell proliferation and the development of breast cancer. Here, the effect of mifepristone on cell proliferation in human breast tissue in vivo was studied in premenopausal women. METHODS: A group of 30 women, scheduled for surgical treatment of leiomyomas, were randomized to either 50 mg mifepristone or placebo every other day, for 3 months. Fine needle aspiration biopsies were obtained at baseline and after 3 months. Immunocytochemical analysis of Ki-67 was performed to reflect breast epithelial cell proliferation. Samples from 14 women were included in the final analyses. RESULTS: The Ki-67 index was significantly reduced after mifepristone treatment compared with baseline (P = 0.012). Furthermore, less individual variation in the Ki-67 index was seen in the mifepristone group. Treatment with mifepristone did not affect cortisol levels, whereas an increase in serum testosterone was noted. Breast symptoms like soreness and swelling were reduced, whereas the incidence of flushes increased. CONCLUSIONS: The ability of mifepristone to block breast epithelial cell proliferation in premenopausal women may prove beneficial when used for contraceptive purposes or for other gynaecological indications. Future studies should address a possible antiproliferative effect in the post-menopausal breast tissue during hormone replacement therapy. Our results implicate a possible protective effect of mifepristone on the breast epithelium. ClinicalTrials.gov NCT00579475.
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Mama/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Antagonistas de Hormonas/farmacología , Mifepristona/farmacología , Biopsia con Aguja Fina , Mama/citología , Mama/patología , Método Doble Ciego , Femenino , Hormonas Esteroides Gonadales/sangre , Antagonistas de Hormonas/efectos adversos , Humanos , Antígeno Ki-67/análisis , Ciclo Menstrual/efectos de los fármacos , Mifepristona/efectos adversos , PremenopausiaRESUMEN
BACKGROUND: The mammary stroma is important for modulating epithelial breast cell response to sex steroid hormones. Proteoglycans, such as syndecan-1, promote the integration of cellular signals. MATERIALS AND METHODS: The immunohistochemical expression of syndecan-1 and of the androgen receptor (AR) was analyzed in paired samples of cancer and adjacent normal tissue from postmenopausal women. RESULTS: Normal and cancer tissue showed dramatic differences in the expression of syndecan-1. In malignant breast stroma, mean values were more than 10-fold higher than in normal tissue (p<0.001). There was also a marked redistribution from the epithelium to the stroma. The expression of AR was on average 2-fold higher in cancerous than in normal tissue (p<0.01). CONCLUSION: Breast cancer patients have very different prognoses. Syndecan-1 and the AR may be new molecular markers relevant to clinical outcome. The redistribution from the epithelium and the dramatic increase of syndecan-1 in cancerous stroma may be related to the natural history of the disease.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Neoplasias de la Mama/metabolismo , Mama/metabolismo , Posmenopausia/metabolismo , Sindecano-1/biosíntesis , Anciano , Células Epiteliales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Receptores Androgénicos/biosíntesis , Células del Estroma/metabolismoRESUMEN
The 11q13 region is amplified in approximately 15% of all breast tumors. Situated in this region are the cyclin D1 gene (CCND1) and the p-21-activated kinase 1 (PAK1) gene. Both genes encode proteins shown to activate the estrogen receptor (ER), leading to transcription of CCND1 and other ER-responsive genes. Here, we investigate the prognostic and treatment predictive role of CCND1 and PAK1 gene amplification in postmenopausal breast cancer patients randomized to tamoxifen treatment or no adjuvant treatment. Amplification of CCND1 and PAK1, assessed by real-time PCR, was observed in 12.5 and 9.3%, respectively. Amplification of PAK1 was seen in 37% of the CCND1-amplified tumors, indicating coamplification (P<0.001). In ER-positive patients, amplification of at least one of the genes indicated a reduced recurrence-free survival (P=0.025). When response to tamoxifen treatment was analysed, patients with PAK1 amplification showed decreased benefit from the drug (ER+; relative risk ratio (RR)=1.62; 95% confidence interval (CI), 0.47-5.55) compared to patients without amplification (ER+; RR=0.53; 95% CI, 0.32-0.88). This was not evident for CCND1 amplification. We show that PAK1 may be a predictor of tamoxifen resistance and furthermore, we do not discard PAK1 as a potential candidate oncogene in the 11q13 amplicon. In addition, we show that high pak1 protein levels may predict tamoxifen insensitivity.
Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Ciclinas/genética , Resistencia a Antineoplásicos , Recurrencia Local de Neoplasia/diagnóstico , Tamoxifeno/uso terapéutico , Quinasas p21 Activadas/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Ciclina D , Ciclinas/metabolismo , Ciclofosfamida/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Amplificación de Genes , Humanos , Metotrexato/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Posmenopausia , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Quinasas p21 Activadas/metabolismoRESUMEN
Postmenopausal hormone therapy (HT) may increase breast cancer risk and influence tumor characteristics. We investigated 321 postmenopausal women aged 50-65 years, with breast cancer, diagnosed and treated at Radiumhemmet, Karolinska Hospital, during 1993-1997. In women using HT (n =90) estrogen receptor concentration (ER) at diagnosis were lower than in non-users (n =135) (1.17 vs 1.70 fmol/microg; p <0.05). HT users also had a tendency to less multifocal (5 vs 12%) (p <0.05) and metastatic disease (5% vs 2%) however this was not statistically significant. The estrogen receptor expression is always considered in the judgement on hormone dependency and the clinical decision on adjuvant endocrine therapy. A suppression of ER during HT could tentatively influence the treatment decisions in breast cancer patients and maybe disregard patients from endocrine treatment.
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Neoplasias de la Mama/metabolismo , Terapia de Reemplazo de Estrógeno/efectos adversos , Receptores de Estrógenos/antagonistas & inhibidores , Neoplasias de la Mama/patología , Regulación hacia Abajo , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia , Receptores de Estrógenos/análisisRESUMEN
BACKGROUND: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome. PATIENTS AND METHODS: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH). RESULTS: Q-PCR and RNA-EP offered similar sensitivity (90% versus 77%), specificity (93% versus 95%), and negative (99% versus 98%) and positive (63% versus 61%) predictive values for HER2 determinations. Analyses of relapse-free survival (RFS) and overall survival on the basis of 5 and 10 years of follow-up indicated equivalent hazard ratios for all three techniques. In contrast to IHC/CISH, both Q-PCR and RNA-EP analyses of HER2 also gave statistically significant results regarding RFS and breast cancer-corrected survival after 10 years of follow-up. CONCLUSION: The use of RNA-EP and Q-PCR to analyze HER2 in frozen and formalin-fixed breast cancer samples may be an alternate approach to IHC in combination with FISH/CISH.
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Genes erbB-2 , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN/análisis , Receptor ErbB-2/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Pronóstico , Recurrencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Análisis de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE: To analyze the expression of Syndecan-1 in dense and non-dense human breast tissue. METHODS: Specimens of histologically normal tissue were obtained from postmenopausal women undergoing surgery for breast cancer. Each tissue block was subject to radiological examination and pair-wise samples of dense and non-dense tissue were collected. Semi-quantitative assessment of immunohistochemical staining intensity for Syndecan-1 and estrogen receptor subtypes was performed. RESULTS: The expression of Syndecan-1 in all tissue compartments was significantly higher in dense than in non-dense specimens. The strongest staining was recorded in stromal tissue. There was a strong correlation between epithelial estrogen receptor alpha and stromal cell Syndecan-1 expression in dense tissue (rs = 0.7; p = 0.02). This association was absent in non-dense tissue. CONCLUSION: An increase of Syndecan-1 in all tissue compartments and a redistribution from epithelium to stroma may be a characteristic feature for dense breast tissue.
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Neoplasias de la Mama/diagnóstico por imagen , Mama/química , Mamografía , Posmenopausia , Sindecano-1/análisis , Mama/patología , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , Epitelio/química , Receptor alfa de Estrógeno/análisis , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Células del Estroma/química , Distribución TisularRESUMEN
Female sex steroids are implied in breast cancer development. The estrogen (ER) and progesterone (PR) receptor subtypes may have different roles to modulate the cellular response. Paired samples of cancer and adjacent normal tissue were collected from postmenopausal women at surgery for ductal breast cancer. The expression of ERa, ERss, PRA and PRB was quantified by immunostaining and digitized image analysis. We found ERss to be significantly reduced in breast cancer tissue (35% vs 50%; p?=?0.001) and there was also a decrease of the ERss/ERa ratio. Among women using hormones at the time of diagnosis tumor tissue showed higher values for both PRB and PRA, as compared to women without such treatment. The results extend previous animal data to be valid also in women. There is evidence that loss of ERss expression may relate to estrogen dependent tumor progression. Increased PR expression could possibly relate to breast cancer risk during combined estrogen/progestogen treatment.
Asunto(s)
Carcinoma Ductal de Mama/genética , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Regulación Neoplásica de la Expresión Génica , Posmenopausia , Receptores de Progesterona/genética , Anciano , Anciano de 80 o más Años , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Progresión de la Enfermedad , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Inmunohistoquímica , Persona de Mediana Edad , Proyectos Piloto , Receptores de Progesterona/metabolismoRESUMEN
OBJECTIVE: To use the fine-needle aspiration (FNA) biopsy technique to compare the effects of tibolone, conventional hormone replacement therapy (HRT) and placebo on breast cell proliferation in postmenopausal women. METHODS: A total of 91 women were randomized to receive either estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo for 6 months in a prospective double-blind trial. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. RESULTS: From the 83 women who completed the study, a total of 166 FNA biopsies were obtained, and 118 of these aspirates (71%) were evaluable for MIB-1 content. Women with assessable biopsies were younger, had a lower body mass index, and had higher levels of sex hormone binding globulin and insulin-like growth factor-I than women in whom the cell yield was insufficient. During treatment with E2/NETA, there was an increase in proliferation (percentage of MIB-1) from a mean value of 2.2 to 6.4% after 6 months (p < 0.01). No significant changes were recorded during treatment with tibolone or placebo. There was a negative association between proliferation and serum levels of total (r(s) = -0.29, p < 0.05) and free (rs = -0.31, p < 0.03) testosterone. CONCLUSIONS: Tibolone seems to have little influence on breast cell proliferation.
Asunto(s)
Mama/citología , Mama/efectos de los fármacos , Moduladores de los Receptores de Estrógeno/farmacología , Terapia de Reemplazo de Estrógeno , Noretindrona/análogos & derivados , Norpregnenos/farmacología , Anciano , Anticuerpos Monoclonales , Biopsia con Aguja , División Celular/efectos de los fármacos , Anticonceptivos Sintéticos Orales/farmacología , Método Doble Ciego , Estradiol/farmacología , Femenino , Humanos , Antígeno Ki-67 , Persona de Mediana Edad , Noretindrona/farmacología , Acetato de Noretindrona , Estudios ProspectivosRESUMEN
Given the promise of rich biological information in microarray data we will expect an increasing demand for a robust, practical and well-tested methodology to provide patient prognosis based on gene expression data. In standard settings, with few clinical predictors, such a methodology has been provided by the Cox proportional hazard model, but no corresponding methodology is available to deal with the full set of genes in microarray data. Furthermore, we want the procedure to be able to deal with the general survival data that include censored information. Conceptually such a procedure can be constructed quite easily, but its implementation will never be straightforward due to computational problems. We have developed an approach that relies on an extension of the Cox proportional likelihood that allows random effects parameters. In this approach, we use the full set of genes in the analysis and deal with survival data in the most general way. We describe the development of the model and the steps in the implementation, including a fast computational formula based on a subsampling of the risk set and the singular value decomposition. Finally, we illustrate the methodology using a data set obtained from a cohort of breast cancer patients.
Asunto(s)
Interpretación Estadística de Datos , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Modelos de Riesgos Proporcionales , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , PronósticoRESUMEN
PURPOSE: To assess the value of fine-needle aspiration cytology in the diagnostic work-up of lipomatous tumors of the extremities and trunk, and to identify specific radiological features that could aid in the preoperative evaluation. MATERIAL AND METHODS: 175 patients with subfascial lipomatous tumors who had undergone preoperative magnetic resonance imaging or computed tomography and fine-needle aspiration cytology were studied. The percentage of fat within the lesion was visually graded from the images as: none, 1-75%, 75-95%, or 95-100%. The histological and cytological diagnoses were compared and in discordant cases the radiological images were re-reviewed. RESULTS: There was cytological and histological concordance in 96% of lipomas and in 85% of atypical lipomatous tumors (ALT) and liposarcomas. Most discordant cases exhibited 1-75% fat. Radiological review suggested that cytological sampling problems due to tumor heterogeneity were the main cause of diagnostic difficulties. The majority of tumors with less than 75% fat were liposarcomas, and in no liposarcoma was the fat content higher than 75%. Both ALT and lipoma were found in the 95-100% group. CONCLUSION: Cytology can be highly accurate in the diagnosis of lipomatous tumors, including ALT; however, critical comparison with the radiological findings increases diagnostic security. In tumors with fat content visually assessed as less than 75% of the tumor volume, liposarcoma is the most likely diagnosis and a cytological diagnosis of ALT or lipoma should be questioned. In lesions with 75-95% fat, liposarcoma is unlikely, but FNAC is still indicated for safety. In lesions with 95-100% fat, FNAC is only indicated if the differentiation between lipoma and ALT influences the treatment strategy.
Asunto(s)
Lipoma/diagnóstico por imagen , Lipoma/patología , Liposarcoma/diagnóstico por imagen , Liposarcoma/patología , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To determine the prevalence and histology of adnexal cysts in autopsy material from postmenopausal women. METHODS: The study included 104 adnexa from 52 consecutive women with a mean age of 79 (range, 64-96) years, who underwent autopsy and died from causes other than gynecological cancer or intraperitoneal cancer of extragenital origin. The adnexa were removed, put in sterile saline in separate plastic containers and examined sonographically using an 8-MHz transvaginal transducer. Each lesion detected at ultrasound examination was measured with calipers on the frozen ultrasound image and was classified according to its ultrasound morphology. The adnexa were then put in 4% formaldehyde solution and sent for histological examination. RESULTS: At ultrasound examination, 56% (29/52) of the women had adnexal lesions, cysts being detected in 54% (28/52) and solid lesions in 12% (6/52). At least one adnexal cyst with a largest diameter of 2-10 mm, > 10 mm, > 20 mm, > 30 mm and > 40 mm, respectively, was found in 33% (17/52), 21% (11/52), 12% (6/52), 8% (4/52) and 4% (2/52) of the women. The largest lesion measured 65 mm in diameter. At ultrasound examination we found 36 intra-ovarian cysts (26 inclusion cysts, three cystically degenerated corpora albicantia, five simple cysts, one serous cystadenoma and one 3-mm cyst not confirmed by the pathologist), 19 extra-ovarian cysts (all simple cysts according to the pathologist), five solid intra-ovarian lesions (two fibromas, one cystadenofibroma, one Brenner tumor and one case of dystrophic calcification), and one solid extra-ovarian lesion (fibroma). In addition, the pathologist detected one 20-mm solid corpus albicans, eight extra-ovarian simple cysts of 1-8 mm, and 77 intra-ovarian inclusion cysts of 1-4 mm. CONCLUSION: Small (< or = 50 mm) benign adnexal cysts and small benign solid tumors are so common in postmenopausal women that their presence may be regarded as normal. Our results support conservative management of adnexal lesions with benign ultrasound morphology incidentally detected at ultrasound examination in postmenopausal women.