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1.
Ann Surg Oncol ; 22(12): 3853-60, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25777085

RESUMO

BACKGROUND: When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion. METHODS: The SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed. RESULTS: From May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56-77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion. CONCLUSIONS: Underestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Excisão de Linfonodo , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Linfonodos/cirurgia , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Prospectivos , Receptor ErbB-2/análise , Análise Serial de Tecidos , Procedimentos Desnecessários , Adulto Jovem
2.
Pediatr Blood Cancer ; 61(2): 253-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23940114

RESUMO

PURPOSE: Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment. METHODS: This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment. RESULTS: At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5-23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6-46.8%) and 32% (95%CI: 12.9-52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT. CONCLUSION: In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Bleomicina/administração & dosagem , Criança , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Lactente , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Neoplasias Testiculares , Vimblastina/administração & dosagem , Adulto Jovem
3.
Breast Cancer Res Treat ; 131(2): 517-25, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22037787

RESUMO

The aim of this study was to prospectively evaluate the predictive value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG-PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV(max)). Pts were classified as non-responders (NR) when the decrease of SUV(max) in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV(max) decrease according to histological response was -52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Fluordesoxiglucose F18 , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Falha de Tratamento
4.
J Neurooncol ; 105(2): 309-15, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21547396

RESUMO

The incidence of leptomeningeal metastases (LM) in patients with breast cancer (BC) is increasing as a result of increased screening and improved patient survival. However, the median survival time after diagnosis of LM is between 5 weeks (without any treatment) and 5 months (for aggressively treated patients). In an attempt to identify clinicopathological risk factors for LM, we carried out a case-control study of 100 women with BC. Fifty patients with BC and LM were enrolled and an additional 50 patients with BC and no CNS metastases including leptomeningeal spread were selected as controls. Patients who had developed LM were selected between December 2006 and August 2008. The control group was matched for: age at diagnosis, year of diagnosis, and initiation of chemotherapy at BC diagnosis. The ILC type (P = 0.03), ER-negative (P = 0.01) and PR-negative status (P = 0.03), and initial M+ status at BC diagnosis (P = 0.008) tended to be more frequent in LM patients. These characteristics should lead to early appropriate assessments being performed in this targeted population when a neurological complaint appears, in order to detect LM as soon as possible.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Meníngeas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias Meníngeas/mortalidade , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida
5.
Breast Cancer Res Treat ; 121(1): 23-33, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19565332

RESUMO

Parvovirus H-1 (H-1 PV) preferentially replicates in malignant cells resulting in their death by cytolysis. It has often been considered a potential candidate for use in novel anticancer therapy. To evaluate its potential in a model of natural tumors, we assayed in vitro the effect exerted by H-1 PV on short-term cultures derived from breast tumor samples freshly excised from patients. Our results show that H-1 PV effectively kills tumor-derived cells, whereas normal tissue-derived cells showed no H-1 PV-induced cytopathic effects (CPE). We also determined that the H-1 PV sensitivity (up to 67% sensitive cultures) is related with the quantities of virus assayed. We further examined the expression and phosphorylation state of the parvoviral nonstructural protein 1 (NS1), known to be associated with parvoviruses-induced CPE. Both appear to be impaired in normal tissue-derived cells and resistant cultures. Finally, we show that H-1 PV sensitivity in cultures correlates significantly with higher tumor grades (Nottingham combined histologic grade 2 or 3). This report confirms that H-1 PV can efficiently induce CPE in primary breast tumor cells in vitro. It identifies tumor characteristics representing potential criteria for recruiting patients for clinical evaluation of H-1 PV antitumor effects.


Assuntos
Neoplasias da Mama/virologia , Parvovirus H-1 , Terapia Viral Oncolítica/métodos , Animais , Western Blotting , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Células Cultivadas , Feminino , Células HeLa , Humanos , Camundongos , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Breast J ; 16(5): 464-71, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20722651

RESUMO

The aim of this study was to compare the complete pathologic response (CPR) rate in 56 nonmetastatic inflammatory breast cancer patients according to the classification used and to look for a correlation between the CPR and overall survival. Initial biopsies and mastectomy specimens were reviewed by the same pathologist. The clinical response rate was 75%. A CPR was observed in 11 cases according to Sataloff, three according to Chevallier and five according to the NSABP. There was no correlation between the clinical and pathologic responses and none of them was predictive of relapse free survival or overall survival. We propose a standardization of the pathologic process of the mastectomy specimens so that a CPR has a clear definition across the institutions, with a good reproducibility whatever the classification used.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Inflamatórias Mamárias/tratamento farmacológico , Neoplasias Inflamatórias Mamárias/patologia , Recidiva Local de Neoplasia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Resultado do Tratamento
7.
Ann Pathol ; 30(5): 357-73, 2010 Oct.
Artigo em Francês | MEDLINE | ID: mdl-21055523

RESUMO

In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS' guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs).


Assuntos
Neoplasias da Mama/química , Neoplasias da Mama/patologia , Receptor ErbB-2/análise , França , Humanos , Imuno-Histoquímica/normas , Hibridização In Situ/normas , Controle de Qualidade , Registros
8.
Radiother Oncol ; 90(1): 23-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18692927

RESUMO

PURPOSE: The MammoSite is a device that was developed with the goal of making breast-conserving surgery (BCT) more widely available. Our objective was to evaluate the MammoSite device performances after an open cavity placement procedure and quality of life in highly selected patients with early-stage breast cancer. METHODS AND MATERIALS: From March 2003 to March 2005, 43 patients with T1 breast cancer were enrolled in a phase II study. The median age was 72 years. Twenty-five (58%) patients were treated with high-dose rate brachytherapy using the MammoSite applicator to deliver 34Gy in 10 fractions. The main disqualifying factor was pathologic sentinel node involvement (10/43; 23%). There were no device malfunctions, migration or rupture of the balloon. RESULTS: After a median follow-up of 13 months, there were no local recurrences and one contralateral lobular carcinoma. Seventeen (68%), 13 (52%), 8 (32%), 5 (20%) and 2 (8%) patients had erythema, seroma, inflammation, hematoma and sever infection, respectively. Only 2 patients developed telangiectasia. At 1 year the rate of "good to excellent" cosmetic results was 84%. Significant changes in QoL were observed for emotional and social well-being between 3 and 12 months. At 24 months, only emotional well-being subscore changes were statistically significant (p=0.015). CONCLUSIONS: Our data in patients older than 60 years support the previously published data. Histologic features were the main disqualifying criteria. With higher skin spacing levels we observed very low incidence of telangiectasia. QoL evaluation indicates that baseline scores were satisfactory. Changes concerned emotional and social well-being.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Cateterismo , Qualidade de Vida , Idoso , Braquiterapia/efeitos adversos , Braquiterapia/instrumentação , Neoplasias da Mama/patologia , Fracionamento da Dose de Radiação , Estética , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Satisfação do Paciente , Biópsia de Linfonodo Sentinela , Estatísticas não Paramétricas , Resultado do Tratamento
9.
Clin Cancer Res ; 12(7 Pt 1): 2088-94, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16609020

RESUMO

PURPOSE: Leptin and obesity are clearly related, and obesity is associated with an increased risk of breast cancer. We therefore measured the expression of leptin and its two main receptor isoforms, OBR-L and OBR-S, in 322 breast cancers. We analyzed their relations with the classical prognostic factors and with survival to establish their links with breast cancer. EXPERIMENTAL DESIGN: The expression of leptin and its receptors was quantified by real-time reverse transcription-PCR, using TaqMan fluorogenic probes and an ABI PRISM 7700 sequence detector system (Applied Biosystems, Courtaboeuf, France). TATA box binding protein was used to normalize expression. The human breast cancer cell, SK-BR-3, expressing the three targets, was chosen as the calibrator sample (i.e., target expression = 1). RESULTS: All the tumors expressed both receptors, and 318 of 322 expressed leptin. These three variables correlated positively with each other and with estradiol and progesterone receptors, whereas they correlated negatively with histoprognostic grading and tumor diameter. OBR-L/OBR-S expression was inversely correlated with progesterone receptors. Patients with elevated OBR-S expression had longer relapse-free survival (P = 0.008), whereas high OBR-L/OBR-S was associated with a shorter relapse-free survival (P = 0.05). In Cox multivariate analyses, OBR-S maintained its prognostic value (P = 0.02; relative risk, 0.51). CONCLUSIONS: This study shows that (a) almost all of the breast cancers coexpress leptin and its two main isoforms of receptors, suggesting that the human epithelial breast cancer cells respond to leptin acting via an autocrine pathway; (b) high expression levels of leptin and leptin receptors are biological markers of a more differentiated phenotype; and that (c) OBR-S is an independent prognostic factor.


Assuntos
Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Leptina/genética , RNA Mensageiro/biossíntese , Receptores de Superfície Celular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Receptores para Leptina , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida
10.
Oncol Lett ; 12(2): 1422-1428, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27446447

RESUMO

Tumor blood vessels participate in the immune response against cancer cells and we previously used pre-clinical models to demonstrate that egfl7 (VE-statin) promotes tumor cell evasion from the immune system by repressing endothelial cell activation, preventing immune cells from entering the tumor mass. In the present study, the expression levels of egfl7 and that of ICAM-1 as a marker of endothelium activation, were evaluated in peritumoral vessels of human breast cancer samples. Breast cancer samples (174 invasive and 30 in situ) from 204 patients treated in 2005 were immunostained for CD31, ICAM-1 and stained for egfl7 using in situ hybridization. The expression levels of ICAM-1 and egfl7 were assessed in peritumoral areas using semi-quantitative scales. There was a strong and significant inverse correlation between the expression of ICAM-1 and that of egfl7 in CD31+ blood vessels. When the ICAM-1 score increased, the egfl7 score reduced significantly (P=0.004), and vice-versa (Cuzick's test for trend across ordered groups). In order to determine which gene influenced the other gene between egfl7 and ICAM-1, the expression levels of either gene were modulated in endothelial cells. Egfl7 regulated ICAM-1 expression while ICAM-1 had no effects on egfl7 expression in the same conditions. Altogether, these results provide further results that egfl7 serves a regulatory role in endothelial cell activation in relation to immune infiltration and that it is a potential therapeutic target to consider for improving anticancer immunotherapies.

11.
Am J Clin Oncol ; 25(6): 561-4, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12477998

RESUMO

Twenty-seven patients with recurrent soft-tissue sarcoma (STS) entered a multicenter study to determine the efficacy of the combination paclitaxel 200 mg/m and epirubicin 75 mg/m administered every 21 days. Patient characteristics included the following: 14 women and 13 men, median age of 52 years, 12 patients had local recurrence and 20 had metastasis. Eighteen patients had previously received chemotherapy for recurrent disease. The main grade III to IV hematologic toxicities were neutropenia (70%), anemia (3.7%), and thrombocytopenia (7.4%). Febrile neutropenia occurred in 5 patients (18.5%). Severe nonhematologic toxicities were rare. Two patients had a partial response (7.4%; 95% CI: 2.6-12.2%), with a median response duration of 3 and 5 months. Six patients had stable disease (22.2%), and 19 had progressive disease (70.5%). The median overall survival from study inclusion was 8 months. This study suggests the association paclitaxel-epirubicin does not increase the known activity of anthracycline in recurrent STS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Terapia de Salvação , Sarcoma/secundário , Análise de Sobrevida
12.
Bull Cancer ; 90(2): 177-80, 2003 Feb.
Artigo em Francês | MEDLINE | ID: mdl-12660136

RESUMO

OBJECTIVE: To perform sentinel node with local anaesthesia in the breast carcinoma without frozen section. So we used definitive histological and immunohistochemical results of sentinel node the day of conserving surgery with complete axillary lymph node dissection under general anaesthesia in case of involved nodes. METHODS: Patients with a stage TNM > T1 or N1, a multicentric breast cancer, a neoadjuvant chemotherapy, an allergy, an obesity or no detection of hot sentinel node were excluded. Patients in ambulatory surgery had scintigraphy 3 hours after injection of radiotracer. If we had a hot sentinel node, we applied Emla 5% cream on the areolar and axillary site and gave midazolam. We performed an intradermal injection of 2 ml of xylocaine with adrenaline above cancer and in the subareolar site in case of non-palpable cancer. With the same needle, we injected 2 ml of blue dye. We injected so 2 ml of xylocaine with adrenaline in the axillary hot spot. We completed local anaesthesia with 16 ml of xylocaine with adrenaline step by step on the route that intraoperative gamma probe showed us. RESULTS: We performed 17 patients (52.6 years [38-62]; body mass index = 23.7 [20-34.1], size of tumour = 10.8 mm [1-25]). We detected 100% of sentinel node. We had a secondary haematoma which was evacuated. CONCLUSION: Perform sentinel node under local anaesthesia is possible for patients with no obesity but radio tracer is absolutely necessary.


Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Adulto , Anestésicos Locais , Axila , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos
13.
Bull Cancer ; 90(10): 887-95, 2003 Oct.
Artigo em Francês | MEDLINE | ID: mdl-14706917

RESUMO

Little is known about epidemiology of adults soft tissue and visceral sarcomas (ASTS). The frequency of previous cancers and associated genetic diseases has been analyzed out of 493 ASTS, treated between 1997 and 2002 at Oscar Lambret Cancer Center. Median age is 51, sex ratio is close to 1. Liposarcomas and malignant fibrous histiocytofibromas are the two main types (respectively 104 and 86 cases). Upper and lower limbs are the two main locations (respectively 176 and 75 cases). Fifteen patients had associated genetic disease, including 12 cases of Recklinghausen diseases. 7 out of those 15 patients have neurosarcoma. 30 patients have previous cancers, including 7 breast cancers, 3 lymphomas and 3 chronic lymphocytic leukemias. Four out of those 30 patients have two different previous cancers. 13 patients have radiation-induced sarcomas, after an average 10-year-period, and an average dose of 53 Gy. Undifferenciated sarcomas are the main histologic type (8/13), followed by angiosarcomas (2/13). Radiation-induced sarcomas are located in the chest wall (7/13), in pelvis (2/13) and head and neck (2/13). Those sarcomas are high grade (10 grade III tumours). ASTS epidemiology is complex with different risk factors depending on histologic type.


Assuntos
Doenças Genéticas Inatas/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Sarcoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Doenças Genéticas Inatas/complicações , Histiocitoma Fibroso Benigno/epidemiologia , Humanos , Lipossarcoma/epidemiologia , Masculino , Pessoa de Meia-Idade , Sarcoma/genética , Sarcoma/patologia
14.
Int J Oncol ; 42(4): 1367-75, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23404186

RESUMO

Egfl7 (VE-statin) is specifically expressed by endothelial cells of normal tissues but its expression is deregulated in human cancers. Analysis of expression of Egfl7 protein and transcripts in 211 human breast cancer samples shows that Egfl7 is strongly expressed by breast tumor cells. Egfl7 expression is significantly higher in invasive ductal than in invasive lobular carcinoma. Expression of Egfl7 transcripts is also higher in lower SBR grade lesions and in lesions which are not associated with lymph node invasion. Within the invasive ductal carcinoma sub-population, expression of Egfl7 transcripts is correlated with the SBR score and with the ER+ status. High transcript and Egfl7 protein levels significantly correlate with the absence of axillary lymph node invasion. In lymph nodes, the levels of Egfl7 are correlated with the histological type of the primary lesions; they are higher in ductal than in lobular carcinoma. Egfl7 expression is thus associated with better prognosis factors and with the absence of lymph node invasion in human breast cancer lesions.


Assuntos
Neoplasias da Mama Masculina/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Lobular/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Células 3T3 , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Axila/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama Masculina/patologia , Proteínas de Ligação ao Cálcio , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/secundário , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/secundário , Carcinoma Lobular/mortalidade , Carcinoma Lobular/secundário , Células Cultivadas , Intervalo Livre de Doença , Família de Proteínas EGF , Fatores de Crescimento Endotelial/genética , Feminino , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Especificidade de Órgãos
15.
In Vivo ; 26(6): 1079-86, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23160697

RESUMO

BACKGROUND: Melanoma has the highest rate of spread to the leptomeninges and the incidence of melanoma has been steadily rising. This article describes recent experience at the Lille University Hospital, between 2007 and 2011 and discusses the possibilities for treatment of leptomeningeal metastasis. PATIENTS AND METHODS: Nine patients were diagnosed with leptomeningeal metastasis of melanoma. The standard criteria were used for the diagnosis. The treatment consisted of a combination of intrathecal chemotherapy, systemic chemotherapy and best supportive care. RESULTS: The overall median survival from the time of leptomeningeal metastasis diagnosis was eight weeks (range=1-168 weeks). In two cases, the median overall survival was 104 weeks. For these patients, there was a clear benefit in intrathecal chemotherapy combined with systemic treatment. No complication was observed. CONCLUSION: Despite a poor prognosis, treatment of melanoma leptomeningeal metastasis is needed in order to improve the quality of life, neurological progression-free survival and overall survival of patients.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Melanoma , Neoplasias Meníngeas , Intervalo Livre de Doença , Feminino , Humanos , Lipossomos/administração & dosagem , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/secundário , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Tiotepa/administração & dosagem
16.
Cancer Res ; 71(23): 7176-86, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22037871

RESUMO

Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-γ, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-γ. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control.


Assuntos
Células Endoteliais/imunologia , Fatores de Crescimento Endotelial/imunologia , Proteínas/imunologia , Evasão Tumoral/imunologia , Animais , Proteínas de Ligação ao Cálcio , Adesão Celular/genética , Adesão Celular/imunologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Células Cultivadas , Progressão da Doença , Família de Proteínas EGF , Células Endoteliais/patologia , Fatores de Crescimento Endotelial/genética , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Interferon gama/genética , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-12/metabolismo , Células Jurkat , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos SCID , Metástase Neoplásica/genética , Metástase Neoplásica/imunologia , Metástase Neoplásica/patologia , Proteínas/genética , Evasão Tumoral/genética , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/imunologia
17.
Neuro Oncol ; 12(12): 1318-25, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20716594

RESUMO

Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.


Assuntos
Neoplasias Encefálicas/terapia , Germinoma/terapia , Recidiva Local de Neoplasia/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/patologia , Carboplatina/administração & dosagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Germinoma/patologia , Humanos , Ifosfamida/administração & dosagem , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida , Resultado do Tratamento
18.
J Clin Oncol ; 27(17): 2809-15, 2009 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-19380452

RESUMO

PURPOSE The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/metabolismo , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Docetaxel , Epirubicina/uso terapêutico , Feminino , Humanos , Antígeno Ki-67/genética , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Receptores de Estrogênio/metabolismo , Resultado do Tratamento
19.
Gynecol Oncol ; 103(3): 1091-4, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16890275

RESUMO

OBJECTIVE: Cervical carcinomas mainly spread via lymphatics, stepwise from pelvic to aortic and scalenic lymph nodes. Metastatic nodes are the major prognostic factor in this disease. When scalenic nodes are involved, cervical cancer is considered to be disseminated. Since there is a major discrepancy in reported percentages of metastatic scalene nodes in the literature (0 to 50%), we proceeded to systematic pretreatment scalene node biopsy and then evaluated the validity of this procedure. METHODS: From January 1998 to May 2003, 72 patients with locally advanced cervical carcinoma and no suspicious paraaortic or scalenic nodes (respectively on magnetic resonance imaging and clinically) had a systematic surgical pretreatment lymph node evaluation (retroperitoneal laparoscopic infrarenal paraaortic lymph node dissection and left scalenic lymph node biopsy). Scalene biopsy was examined using hematoxylin/eosin stain and immunohistochemistry (KL1 antibodies). RESULTS: Among the 72 patients, 20 were stage IB2, 4 were IIA, 14 were IIB, 4 were IIIA, 27 were IIIB, 1 was IVA and 2 had a recurrent cervical carcinoma. Fourteen women had histologically confirmed paraaortic metastases (11 macroscopic, 3 microscopic). No metastatic involvement of the scalene nodes was detected. Fifteen patients developed a recurrence within 12 months (3 to 19 months). None of the patients developed scalenic recurrence. CONCLUSION: Left scalene node biopsy does not appear to be mandatory in routine pretherapeutic lymph node evaluation of patients with advanced cervical carcinoma and no clinical suspicious nodes. It may be useful to prove disseminated disease in patients with suspicious clinical nodes or hot spots on PET-scan, if fine needle biopsy is unconclusive.


Assuntos
Excisão de Linfonodo/métodos , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adulto , Idoso , Aorta Abdominal/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Pescoço/patologia , Estadiamento de Neoplasias , Reprodutibilidade dos Testes
20.
Bull Cancer ; 92(11): 983-7, 2005 Nov.
Artigo em Francês | MEDLINE | ID: mdl-16316832

RESUMO

Between February 2001 and March 2003, 542 sentinel lymph node procedures were performed for localised breast carcinoma (T0-T1, N0, M0) without any previous treatment. Frozen sections were performed in 515 cases and they did not reveal metastases in 446 cases. Fifty-two micrometastases < 2 mm and 18 macrometastases were reported by definitive histopathological exam. Axillary clearance was performed in 50/70 patients (38 with micrometastases and 12 for macrometastases). Modalities of histopathological procedure are discussed and particularly number and interval of serial slides with or without immunochemistry ; 81.8% (36/44) of micrometastases were detected on the two first serial sections. Decisional value of axillary clearance performed in case of micrometastases is also evaluated.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico , Biópsia de Linfonodo Sentinela , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Axila , Neoplasias da Mama/cirurgia , Reações Falso-Negativas , Feminino , Secções Congeladas , Humanos , Imuno-Histoquímica , Excisão de Linfonodo , Metástase Linfática/patologia , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Coloração e Rotulagem
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