RESUMEN
The aim of this systematic review was to establish the current status of the subject and find out what scientific evidence we have on the use of autologous plasma concentrates (APCs) and mesenchymal stem cells (MSCs) as complementary therapies at the management of Medication-related Osteonecrosis of the jaw (MRONJ). We performed a literature search of articles published between December 2019 to January 2020 in electronic databases, in accordance to PRISMA system. The variables analyzed were: the number of patients, age, sex, medical history, origin of MRONJ, imaging studies, treatment performed, and evolution of MRONJ. The articles included in the review were grouped into two groups (Group A "Therapy with APCs" and Group B "Therapy with APCs and MSCs"). Newcastle-Ottawa scale (NOS) was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of the 306 patients who were included, 297 belonged to Group A and 9 to Group B. In our sample, women predominated against men and no significant differences in age were observed. Osteoporosis was the most frequent underlying disease in both groups. The most common origin of MRONJ was oral surgery in group A. Conservative surgery was performed in all patients, but complementary treatment was applied in different ways in each group. The resolution of the pathology was achieved in 90% of cases in both groups without significant differences between them. The mean score of the reviewed studies at NOS was 4. There are currently no published scientific data that can sufficiently support the use of APCs and MSCs for the treatment of established MRONJs.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Células Madre Mesenquimatosas , Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Osteonecrosis de los Maxilares Asociada a Difosfonatos/terapia , Femenino , Humanos , Masculino , Trasplante AutólogoRESUMEN
We performed a systematic review of the literature about descending necrotising mediastinitis (DNM) of odontogenic origin. In parallel, a retrospective review of this pathology was carried out in an Oral and Maxillofacial Surgery Service of a reference hospital for a population of 1,100,000 inhabitants. The main objectives were to determine changes in mortality and prevalence of this serious complication. The systematic review included 51 articles with 89 patients and our study comprised seven patients. The period of time with the highest number of cases was between 2000-2009 (38 patients). The percentage of mortality observed was 20.2% in diffuse DNM and 4.9% in localised DNM. Thirty-one patients with DNM in our review were admitted for more than 41 days. Despite evidence of a decrease in DNM cases, publications have increased over the years, but it does not appear to be due to an increase in those of odontogenic origin. The survival of DNM has improved since 1998 and remained stable since then. Despite the low prevalence of this disease, multicentre control studies are needed to achieve better evidence about this entity.
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Mediastinitis , Drenaje , Humanos , Mediastinitis/epidemiología , Mediastinitis/etiología , Necrosis , Estudios RetrospectivosRESUMEN
PURPOSE: The aim of this study was to review the characteristics of 'implant presence-triggered osteonecrosis' (IPTO) in the literature and identify possible differences between IPTOs and 'implant surgery-triggered osteonecrosis' (ISTO). MATERIALS AND METHODS: Reviews using PubMed and the Cochrane Database of Systematic Reviews were performed from 2009-2018; the focus was on medication-related osteonecrosis of the jaw (MRONJ) and dental implants. In addition, the hospital records of all patients presented in our department with IPTO were retrospectively reviewed. In both studies, the following data were collected: the number of patients with ISTO or IPTO, age, gender, location, stage of MRONJ, number of implants involved in MRONJ, the elapsed time between the placement of the implants and the development of MRONJ, applied treatment and the presence of mandibular fractures and progress. RESULTS: The literature review provided 111 articles. Nine of the articles were selected for bibliographic review. The number of osteonecrosis cases was significantly higher in the IPTO group (74 cases) compared with the ISTO group (27 cases). The duration of the anti-resorptive treatment (oral and intravenous) was also longer in the IPTO group. In our centre, seven patients with IPTO were chosen; however, no patients with ISTO were selected. The significant differences between the patients in our series and the information collected in the literature for the IPTO group were the time of ingestion of alendronate, the elapsed time from the placement of the implants to the development of the MRONJ and the number of implants linked to the development of a complication. CONCLUSIONS: The use of antiresorptives causes osteonecrosis in patients with implants that are subjected to functional loading, and this occurs at a higher frequency than what is observed after implant placement surgery.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Implantes Dentales , Humanos , Estudios RetrospectivosRESUMEN
INTRODUCTION: The aim of the present study was to investigate the number of patients with Multiple Myeloma (MM) treated with intravenous Zoledronic Acid who presented an involvement of the jaws by Myeloma that mimicked an osteonecrosis. MATERIAL AND METHODS: A retrospective study was performed in a University Hospital reference for a population of 1.084.000 inhabitants. A 'case' Medication-Related Osteonecrosis of the jaw (MRONJ) was considered when the patient met diagnostic criteria established by the American Association of Oral and Maxillofacial Surgeons (AAOMS, 2014). We recorded data on the underlying disease, medications used, mode of Bisphosphonate administration (oral or intravenous), and timing of medication use. RESULTS: The sample size was 84 cases. 22 patients had MRONJ associated to MM treatment. Histopathological examination of pathological bone was characterized by the presence of necrotic osteitis in 82 patients. Only 2 patients with MRONJ suspicion were finally diagnosed as MM. These cases represented 9.09% of all patients with multiple myeloma initially labeled MRONJ in our hospital. CONCLUSION: The present study has shown that MM can be identified in jaw specimens of patients exposed to Bisphosphonates and clinically diagnosed as osteonecrosis. Biopsy examination should be considered in at least selected cases, for example, before surgical treatment in patients with MM and clinical stage 3 osteonecrosis (due to the detection of malignancy would alter the surgical strategy).
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Mieloma Múltiple , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/epidemiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Difosfonatos/efectos adversos , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Ácido Zoledrónico/efectos adversosRESUMEN
INTRODUCTION: The objective of this study was to investigate the knowledge and capabilities of dentists and dental students in their last year of study in regard to risk factors of medication-related osteonecrosis of the jaw (MRONJ) in Spain. MATERIAL AND METHOD: We conducted a cross-sectional study consisting of a questionnaire survey in Asturias, Spain. The study was divided into three groups: dentists who worked for the public dental health care system (n=32), dentists who worked exclusively as private health care practitioners (n=136), and dental students in their last year (year five) of study (n=38). The quantitative differences in the scores obtained in the resolution of clinical cases between students and dentists were evaluated. Differences between dentists were evaluated depending on number of years in practice, activity (private or public care), and area of specialty. The study tracked the possible differences in the general knowledge of MRONJ among dentists and students and the participants' adherence to the dental clinic guidelines regarding the MRONJ. RESULTS: Students from year five reached a higher score than those dentists with private practice activity (P=0.01). Significant differences between the students and the public health care dentists were not recognized, nor between the latter and the private health care dentists. The lowest percentage of correct answers among participants was related to implant surgery in patients treated with oral aminobisphosphonates. The dentists with more than 20 years of professional experience obtained significantly lower-than-average scores in the resolution of the clinical cases based on clinical guidelines (P=0.01). We did not observe any differences in the average test scores obtained by dentists dependent on their area of expertise. CONCLUSIONS: Knowledge of side effects of antiresorptive drugs decreases with years of professional practice. Training efforts on MRONJ should focus especially on those dentists who practice privately, who have over 20 years of professional experience, and who perform implant surgery on patients at risk of MRONJ.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Actitud , Estudios Transversales , Odontólogos , Difosfonatos , Humanos , España , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The aim of this study was to evaluate the bioactivity of Fullcure compared to porous polyethylene implants (Medpor) in rats prior to custom-made scaffold support manufacturing for mandible segmental defects (MSD) reconstruction in sheep. METHODS: Twelve Fullcure and Medpor laminaes were implanted in the left and right dorsum respectively of six wistar rats. Toxicity was assessed by skin, kidney and liver histopathology three months post-implantation. Computed Tomography (CT) was carried out in order to assess radiological differences between implants. Fullcure containers were subsequently manufactured by CAD/CAM to hold scaffold cylinders for MSD reconstruction in sheep. RESULTS: No statistical differences were observed in tissue response between implants. Fullcure radiodensity was higher than Medpor (P<0.05). Fullcure manufactured support was successfully used for mandible repair in sheep. Nevertheless, the manufactured container did not accomplish the goal of guiding new bone formation according to the mandible shape. CONCLUSIONS: Fullcure showed similar biocompatibility and stronger radiodensity than Medpor. Despite its cheaper price and endless 3D-printing possibilities as scaffold holder for mandible reconstruction, further animal studies are needed to ensure Fullcure biocompatibility as implantable biomaterial.
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Reconstrucción Mandibular , Animales , Diseño Asistido por Computadora , Mandíbula , Ratones , Impresión Tridimensional , Prótesis e Implantes , Ratas , OvinosRESUMEN
No disponible
Asunto(s)
Neurociencias/historia , Neurociencias/métodos , Bacteriología/educación , Bacteriología/ética , Bacteriología/historia , Neurofisiología/historia , Neurofisiología/métodos , Premio NobelRESUMEN
We present the case of a 44 year-old patient, without significant previous medical history, who presented a systemic infection due to Eikenella corrodens following a dental extraction in the context of an agranulocytosis of pharmacological origin due to carbimazole. During admission he was treated with broad-spectrum antibiotics and G-CSF 5 µg/kg/day, undergoing a favorable evolution and receiving hospital discharge on the seventh day. Invasive infections due to Eikenella corrodens that develop bacteriaemia are less than 20%, and are generally secondary to the drainage of previous abscesses and are usually isolated together with other microorganisms; while finding a monomicrobial primary bacteriaemia without the prior existence of endocarditis is exceptional. This is the first case of systemic infection due to this bacteria secondary to dental manipulation, where the state of transitory immunosuppression in which the patient found himself at that time was determinant in causing the disseminated infection.
Asunto(s)
Bacteriemia/microbiología , Eikenella corrodens , Infecciones por Bacterias Gramnegativas/microbiología , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/microbiología , Adulto , Humanos , MasculinoRESUMEN
A patient, without significant previous medical history, who started with diplopia and left palpebral ptosis as the first manifestation of hypophysary metastases of a widely disseminated and previously undetected cancer of pulmonary origin. Together with a histological study of the lesions, the diagnosis was made with specific image tests of the hypophysary area, which detected a neoformation in the sella turca that was invading the left cavernous sinus with erosion of the verso of the sellar, together with the presence of pulmonary nodules and numerous adenopathies. An hypogonadotropic hypogonadism was detected as the only hormonal alteration due to the infiltration of the anterior hypophysis due to the osseous metastases at the base of the cranium. The patient, in spite of receiving several weeks of radiotherapy, suffered a progressive neurological deterioration and died after a few weeks.
Asunto(s)
Adenocarcinoma/complicaciones , Adenocarcinoma/secundario , Blefaroptosis/etiología , Diplopía/etiología , Neoplasias Pulmonares/patología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/secundario , Adenocarcinoma/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/diagnósticoRESUMEN
Se expone el caso de un paciente de 44 años, sin antecedentes de interés, que presentó una infección sistémica por Eikenella corrodens posterior a una extracción dentaria en el contexto de una agranulocitosis de origen farmacológico por carbimazol. Durante el ingreso fue tratado con antibióticos de amplio espectro y G-CSF 5 microg/kg/día con una evolución favorable y alta hospitalaria en el séptimo día. Las infecciones invasivas por Eikenella corrodens, que desarrollan bacteriemia son menos del 20%, generalmente son secundarias a drenaje de abscesos previos y suele aislarse junto a otros microorganismos, siendo excepcional el hallazgo de una bacteriemia primaria monomicrobiana sin la existencia previa de endocarditis. Es el primer caso de infección sistémica por esta bacteria secundaria a manipulación dental, en el que fue determinante el estado de inmunosupresión transitorio en el que se encontraba el paciente en ese momento para causar la infección diseminada(AU)
We present the case of a 44 year-old patient, without significant previous medical history, who presented asystemic infection due to Eikenella corrodens following a dental extraction in the context of an agranulocitosis of pharmacological origin due to carbimazole. During admission he was treated with broad-spectrum antibiotics and G-CSF 5 microg/kg/day, undergoing a favorable evolution and receiving hospital discharge on the seventh day. Invasive infections due to Eikenella corrodens that develop bacteriaemia are less than 20%, and are generally secondary to the drainage of previous abscesses and are usually isolated together with other microorganisms; while finding a monomicrobial primary bacteriaemia without the prior existence of endocarditis is exceptional. This is the first case of systemic infection due to this bacteria secondary to dental manipulation, where the state of transitory immunosuppression in which the patient found himself at that time was determinant in causing the disseminated infection(AU)
Asunto(s)
Humanos , Masculino , Adulto , Bacteriemia/microbiología , Eikenella corrodens/aislamiento & purificación , Periodontitis/complicaciones , Agranulocitosis/complicaciones , Extracción Dental/efectos adversos , Carbimazol/uso terapéuticoRESUMEN
La diabetes MODY-5 es un tipo de diabetes monogenica infrecuente, causada por mutación en el gen del factor de transcripción nuclear hepático 1-beta (HNF-1¦Â). Esta mutación puede ser de tipo puntual o bien corresponder a delecciones grandes, y a su vez, puede aparecer de novo por mutación espontanea o bien ser transmitida de forma hereditaria con caracter autosomicodominante. Está asociada con un alto riesgo de complicaciones microvasculares de aparición temprana en las personas afectas, así como con alteraciones renales características del tipo quistes y anomalías del tracto genital, que estan presentes incluso antes del nacimiento. Por ello, está justificado hacer pruebas de detección para las mutaciones de HNF-1 en diabíticos no obesos, sobre todo, cuando existen alteraciones renales o genitales asociadas, sin tener en cuenta losantecedentes familiares (AU)
MODY-5 diabetes is an infrequent type of monogenic diabetes, caused by mutation in the gene of the nuclear hepatic transcription factor 1-beta (HNF-1¦Â).This mutation can be of a momentary type or it might correspond to big deletions, and, in its turn, it can appear due to spontaneous de novo mutation or it can be transmitted by hereditary with an autosomal dominant character. It is associated with a high risk of microvascular complications that appear early in affected people, as well as with characteristic renal alterations of the cyst type, and anomalies of the genital tract, which are present even before birth. That is why it is justified to carry out detection tests for HNF-1¦Â mutations in non-obese diabetics, above all when there are associated renal or genital alterations, without consideration of family antecedents (AU)
Asunto(s)
Humanos , Femenino , Adulto , Diabetes Mellitus/genética , Factor Nuclear 1-beta del Hepatocito/genética , Microvasos/fisiopatología , Anomalías Urogenitales/epidemiologíaRESUMEN
AIMS: This study aimed to investigate the expression of matrix metalloproteases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ (DCIS). METHODS: We used inmunohistochemistry to compare the expression of MMPs and TIMPs in tumor or stromal cells for 50 pure DCIS and 12 DCIS with microinvasive foci. RESULTS: Score values for collagenase-1 (MMP-1), membrane type 1 MMP (MMP-14), and TIMP-1, were significantly higher in pure DCIS than in DCIS with microinvasive foci, whereas stromalysin-3 (MMP-11) expression was significantly higher in DCIS with microinvasive foci. Both fibroblasts and mononuclear inflammatory cells (MICs) surrounding pure DCIS showed more frequently expression of MMP-1, MMP-14, and TIMP-3, whereas MMP-11 expression was more frequent in MICs of microinvasive tumors. MICs of microinvasive foci more frequently showed the expression of gelatinase A (MMP-2), MMP-11, collagenase-3 (MMP-13), and TIMP-1, than MICs surrounding pure DCIS; whereas peri-ductal MICs and fibroblasts from pure DCIS expressed TIMP-3 more commonly than these cells at microinvasive foci. CONCLUSIONS: There are significant differences in the expression of MMPs and TIMPs, so in tumor cells and stromal cells, between pure DCIS and DCIS with microinvasive foci. Therefore, these staining patterns might display potential applications as biological markers, such as in evaluating microinvasion in resection specimens of breast tumors.
Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Metaloproteasas/biosíntesis , Células del Estroma/metabolismo , Inhibidores Tisulares de Metaloproteinasas/biosíntesis , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/enzimología , Carcinoma Intraductal no Infiltrante/cirugía , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Metaloproteasas/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/patología , Células del Estroma/enzimología , Células del Estroma/patología , Análisis de Matrices Tisulares , Inhibidores Tisulares de Metaloproteinasas/metabolismoRESUMEN
PURPOSE: Metalloproteases (MMPs) and their tissue inhibitors of metalloproteases (TIMPs) are involved in several key aspects of tumoral growth, invasion and metastasis. The purpose of this study was to characterize on how the different histological types of breast cancer differ in the expression of several components of this enzymatic system. METHODS: An immunohistochemical study was performed in 50 ductal, 23 lobular, 14 mucinous, 7 tubular, 4 papillary and 5 medullary invasive carcinomas, using tissue arrays and specific antibodies against 7 MMPs and 3 tisullar TIMPs. Staining results were categorized by means of a specific software program (score values). RESULTS: Carcinomas of the ductal type showed higher score values for MMPs and TIMPs than the other histological types; whereas mucinous carcinomas had lower scores values for expressions of the majority of these proteins. Stromal fibroblasts were more frequently positive for MMP-1, -7 and -13 and TIMP-1 and -3, when present in carcinomas of the ductal type than in other histological types of breast carcinomas. Stromal mononuclear inflammatory cells were more frequently positive for MMP-1 and TIMP-3, but more often negative for MMP-7, -9 and -11, when located in carcinomas of the ductal type than in other histological types of breast carcinomas. CONCLUSIONS: We found variations in MMP/TIMP expressions among the different histological subtypes of breast carcinomas suggesting differences in their tumor pathophysiology.
Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Metaloproteasas/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Carcinoma Medular/metabolismo , Carcinoma Medular/patología , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Matrices TisularesRESUMEN
BACKGROUND: Several studies have suggested the significance of some metalloproteases in the malignant behaviour of hepatocellular carcinoma. AIMS: To evaluate the liver expression of MMPs and their tissular inhibitors in patients with HCC. METHODS: An immunohistochemical study using tissue microarrays on samples obtained from 30 HCC patients, with antibodies against MMPs (1, 2, 7, 9, 11, 13 and 14) and TIMPs (1, 2 and 3) was performed. Results were correlated with various clinico-pathological findings and with overall survival. RESULTS: MMP-1 is mainly expressed by stromal cells, and MMP-13, TIMP-1 and TIMP-2 by inflammatory cells. A positive correlation between MMP-1 expression and larger size tumours (p<0.01) was found. Increased TIMP-2 expression was associated with higher preoperative serum levels of alpha-fetoprotein (p<0.01). Unsupervised hierarchical clustering for total score values designated two groups, one of them characterised by high MMPs and TIMPs expressions, including 21 cases (70%) for tumour cell clustering, 5 cases for fibroblasts (16.6%) and 6 cases for inflammatory cells (20%). All patients showing elevated MMPs and TIMPs expression in stromal cells presented a poor prognosis (p<0.05). CONCLUSIONS: High liver MMPs and TIMPs expressions in peritumour stromal cells are related to a poorer prognosis in HCC.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Anciano , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Hígado/citología , Hígado/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Células del Estroma/metabolismo , Análisis de SupervivenciaRESUMEN
An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs -1, -2, -7, -9, -11, -13, -14, and TIMPs -1, -2 and -3. More than 5,000 determinations on cancer specimens from 124 patients with invasive breast cancer were performed at the center of the tumor and the invasive front. Immunostaining for MMPs/TIMPs by fibroblasts was evaluated. To identify specific groups of tumors with distinct expression profiles, the data obtained from both fibroblast populations were analyzed by unsupervised hierarchical cluster analysis. Intratumor stromal fibroblasts more frequently showed expression of MMP-2, -7, and -14, and TIMP-3, but less frequently of MMP-9 than fibroblasts at the invasive front. Multivariate analysis showed that a high profile of MMPs and TIMPs staining in both fibroblast populations was the most potent predictor factor of distant metastases, whereas a low staining profile in fibroblasts was associated with a low risk of metastases.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Fibroblastos/enzimología , Metaloproteinasas de la Matriz/biosíntesis , Inhibidores Tisulares de Metaloproteinasas/biosíntesis , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Análisis por Conglomerados , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Invasividad Neoplásica/patología , Pronóstico , Células del Estroma/enzimología , Análisis de Matrices TisularesRESUMEN
AIMS: To analyse the expression of metalloproteinases (MMPs) and their inhibitors (TIMPs) in ductal carcinoma in situ of the breast (DCIS). METHODS AND RESULTS: An immunohistochemical study was performed in 56 patients with pure DCIS, in 39 with DCIS adjacent to invasive carcinoma (IDC) and 63 patients with T1 IDC, using tissue microarrays and specific antibodies against MMPs and TIMPs. Immunohistochemical results were categorized using a specific software program. The data were analysed by unsupervised hierarchical cluster analysis by each cellular type. IDC showed a higher expression rate of MMP-7 and TIMP-1 than pure DCIS, as well as a higher expression rate of MMP-9 and TIMP-3 than the DCIS component of mixed cases, whereas pure DCIS showed a higher rate of expression of MMP-9 and -11 and TIMP-3 than in the DCIS component of mixed cases. Pure DCIS with a periductal inflammatory infiltrate showed significantly higher MMP-2, -14 and TIMP-1. Dendograms identified two cluster groups with distinct MMP/TIMP expression profiles in neoplastic cells and fibroblastic or mononuclear inflammatory cells surrounding the neoplastic ducts of pure DCIS. CONCLUSIONS: The results indicate the distinct variability in MMP/TIMP expression by DCIS, which may be of potential biological and clinical interest in breast cancer.
Asunto(s)
Neoplasias de la Mama/enzimología , Carcinoma Intraductal no Infiltrante/enzimología , Metaloproteinasas de la Matriz/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Femenino , Humanos , Inmunohistoquímica , Análisis de Matrices TisularesRESUMEN
OBJECTIVES: Gene expression analysis has identified several breast cancer subtypes, including luminal, epidermal growth factor receptor-2 positive (HER2+), and basal-like. To determine if our proposed molecular taxonomy correlates with biological and clinical behavior. This is based on four biological markers: estrogen and progesterone receptors (ER and PR, respectively), HER2 and the epidermal growth factor receptor-1 (HER1), all of them being determined by quantitative assays. STUDY DESIGN: The biological parameters were examined by enzyme immunoassay, radioligand-binding assay or ELISA, in tumors from 787 patients with invasive breast cancer. Patients were prospectively evaluated over a median follow-up period of 50 months. Subtype definitions were as follows: luminal (ER+), HER2+ (HER2+, ER-, PgR-) and basal-like (HER2-, ER-, PgR-). In addition, we divided basal tumors into two groups based on their HER1 status. RESULTS: A 55.8% of tumors were of luminal type, 11.9% basal-like HER1+, 10.7 basal-like HER1-, and the remainder 21.6% HER2+. Both HER2+ and basal-like subtypes were more frequent in younger and premenopausal women, showing a higher percentage of cases of poorly differentiated tumors and higher S-phase fraction, when compared with those of luminal subtype. Multivariate analysis demonstrated that the subtype of tumor was related to both relapse and overall survival, being those of luminal subtype associated with the best prognosis. CONCLUSIONS: Through the classification of breast tumors in four groups, according to their ER, PgR, HER2 and HER1 status, it is possible to obtain a major division of breast tumors associated with significant differences in biological features and clinical behavior.
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Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Receptor ErbB-2/genética , Neoplasias de la Mama/genética , Receptores ErbB/genética , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Análisis de SupervivenciaRESUMEN
An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5-9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.
Asunto(s)
Neoplasias de la Mama/enzimología , Carcinoma Ductal/enzimología , Carcinoma Ductal/secundario , Leucocitos Mononucleares/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Biomarcadores de Tumor/metabolismo , Western Blotting , Neoplasias de la Mama/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Leucocitos Mononucleares/inmunología , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Tasa de Supervivencia , Análisis de Matrices Tisulares/métodosRESUMEN
AIMS: To evaluate the expression of androgen receptors (AR) and two androgen-induced proteins [apolipoprotein D (ApoD) and pepsinogen C (PepC)] in ductal carcinoma in situ (DCIS) of the breast. METHODS AND RESULTS: AR, ApoD and PepC expression was examined in 28 cases of pure DCIS and in 31 cases of DCIS adjacent to invasive carcinoma of the breast using immunohistochemical methods and then correlated with the architectural subtype, the degree of differentiation and the ostrogen receptor (ER)/progesterone receptor (PgR)/HER-2 status. We found no significant differences between pure DCIS and DCIS adjacent to invasive breast cancer regarding the percentage of positive cases for ApoD (64.3% versus 54.8%), PepC (42.9% versus 48.4%), ER (64.3% versus 58.1%), PgR (60.7% versus 58.1%) and HER-2 (39.3% versus 67.7%). However, there was a significantly higher percentage of AR+ DCIS among those adjacent to invasive carcinomas of the breast than among pure DCIS lesions (93.5% versus 60.9%) (P = 0.009). AR expression did not correlate with architectural subtype, degree of differentiation, or ER/PgR/HER-2/ApoD/PepC status, in cases of pure DCIS, nor in DCIS adjacent to invasive carcinoma of the breast. CONCLUSIONS: AR expression may represent an independent predictive factor in DCIS of the breast.