RESUMEN
Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.
RESUMEN
Diffuse large B-cell lymphoma (DLBCL), the most frequent non-Hodgkin's lymphoma subtype, is characterized by strong biological, morphological, and clinical heterogeneity, but patients are treated with immunochemotherapy in a relatively homogeneous way. Here, we have used a customized NanoString platform to analyze a series of 197 homogeneously treated DLBCL cases. The platform includes the most relevant genes or signatures known to be useful for predicting response to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) in DLBCL cases. We generated a risk score that combines the International Prognostic Index with cell of origin and double expression of MYC/BCL2, and stratified the series into three groups, yielding hazard ratios from 0.15 to 5.49 for overall survival, and from 0.17 to 5.04 for progression-free survival. Group differences were highly significant (p < 0.0001), and the scoring system was applicable to younger patients (<60 years of age) and patients with advanced or localized stages of the disease. Results were validated in an independent dataset from 166 DLBCL patients treated in two distinct clinical trials. This risk score combines clinical and biological data in a model that can be used to integrate biological variables into the prognostic models for DLBCL cases.
RESUMEN
BACKGROUND: Primary cardiac tumors are extremely rare; most are myxomas with a benign prognosis. However, primary sarcomas are highly aggressive and treatment options are limited. Radical surgery is often not feasible and conventional therapies provide only modest results. Due to the rare nature of primary cardiac tumors, there are no proper randomized studies to guide treatment. Their complexity requires alternative approaches in order to improve treatment efficacy. METHODS: We isolated DNA from 5 primary cardiac sarcomas; the quality of DNA from 3 of them was sufficient to perform high-resolution single nucleotide polymorphism (SNP) array analysis. RESULTS: In the present study, molecular karyotyping revealed numerous segmental chromosomal alterations and amplifications affecting actionable genes that may be involved in disease initiation and/or progression. These include chromosomal break flanking AKT2 in undifferentiated pleomorphic rhabdomyosarcoma, chromosomal break in promoter of TERT, and gain of CDK4 and amplification of MDM2 in inflammatory myofibroblastic tumor. We detected segmental break flanking MOS in high-grade myxofibrosarcoma. In addition, the high number of chromosomal aberrations in high-grade myxofibrosarcoma may cause multiple tumor-specific epitopes, supporting the study of immunotherapy treatment in this type of aggressive tumor. CONCLUSION: Our results provide a genetic rationale that supports an alternative, personalized therapeutic management of primary cardiac sarcomas.
RESUMEN
Alpha-methylacyl-CoA racemase (AMACR) expression has been demonstrated in several normal tissues and in diverse types of carcinoma. Our aim was to analyze the immunohistochemical expression of AMACR in the sequence-progression of colonic cancer. We studied 237 cases, including samples of normal mucosa of the colon, adenomas with different degrees of dysplasia, colonic carcinomas, lymph nodes and liver metastases of colonic carcinomas. A scale of intensity and percentage of expression was used to analyze the AMACR immunohistochemical profile. The expression was nearly absent in samples of normal mucosa, increased in both adenomas and carcinomas, decreased in lymph node metastases but was significantly increased in liver metastases.
Asunto(s)
Adenocarcinoma/enzimología , Proteínas de Neoplasias/análisis , Racemasas y Epimerasas/análisis , Adenoma/enzimología , Anciano , Anciano de 80 o más Años , Colon/enzimología , Pólipos del Colon/enzimología , Progresión de la Enfermedad , Femenino , Humanos , Mucosa Intestinal/enzimología , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , MuestreoRESUMEN
La expresión inmunohistoquímica de la alfa-metilacil-CoA racemasa (AMACR) ha sido demostrada en varios tejidos normales y en diferentes tipos de carcinomas. Nuestro objetivo fue analizar la expresión inmunohistoquímica de la AMACR en la secuencia-progresión del carcinoma de colon. Se estudiaron 237 casos, que incluían muestras de mucosa colónica normal, adenomas con distintos grados de displasia, carcinomas de colon, y metástasis ganglionares y hepáticas de carcinoma colónico. Para el análisis de la expresión inmunohistoquímica de la AMACR se utilizó una escala que valoraba la intensidad y el porcentaje de su expresión en el tejido. La expresión fue casi nula en las muestras de mucosa normal, se incrementó en los adenomas y carcinomas, disminuyó de forma significativa en las metástasis ganglionares, pero volvió a aumentar su expresión en las metástasis hepáticas (AU)
Alpha-methylacyl-CoA racemase (AMACR) expression has been demonstrated in several normal tissues and in diverse types of carcinoma. Our aim was to analyze the immunohistochemical expression of AMACR in the sequence-progression of colonic cancer. We studied 237 cases, including samples of normal mucosa of the colon, adenomas with different degrees of dysplasia, colonic carcinomas, lymph nodes and liver metastases of colonic carcinomas. A scale of intensity and percentage of expression was used to analyze the AMACR immunohistochemical profile. The expression was nearly absent in samples of normal mucosa, increased in both adenomas and carcinomas, decreased in lymph node metastases but was significantly increased in liver metastases (AU)
Asunto(s)
Humanos , Masculino , Femenino , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/patología , Carcinoma/diagnóstico , Carcinoma/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Inmunohistoquímica/métodos , Inmunohistoquímica , Alanina Racemasa/análisis , 28599 , Metástasis de la Neoplasia/patología , Racemasas y Epimerasas/análisisRESUMEN
Galectin-1 (GAL-1) is frequently expressed in osteosarcomas. Although a valuable diagnostic marker to differentiate between chondroblastic osteosarcomas and conventional chondrosarcomas, it has not been tested in the Ewing sarcoma family of tumors (ESFTs). We studied by immunohistochemistry GAL-1 expression in 43 osteosarcomas, 23 chondrosarcomas, and 217 genetically confirmed ESFTs using a tissue microarray. GAL-1 was expressed in 78 % of osteosarcomas, 33 % of chondrosarcomas, and 8 % of ESFTs. Osteoblastic and small cell osteosarcoma subtypes expressed GAL-1 in a high percentage of cells when compared with the other histological subtypes, whereas two chondroblastic osteosarcomas were negative. GAL-1 was mainly expressed in high-grade chondrosarcomas (grade III). ESFTs were rarely positive (8 %), and this was not related to the histological subtype nor to the clinical outcome. Although GAL-1 expression distinguishes chondroblastic osteosarcomas from conventional chondrosarcomas and is usually negative in conventional chondrosarcomas, the final diagnosis needs to incorporate histopathology since some chondroblastic osteosarcomas fail to express GAL-1, while high-grade chondrosarcomas are GAL-1 positive. Since GAL-1 is frequently expressed in osteogenic tumors, including small cell osteosarcoma, but rarely positive in ESFTs, its expression seems a valuable tool for distinguishing between these lesions. GAL-1 immunoexpression is not indicative of prognosis in ESFT.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/diagnóstico , Galectina 1/metabolismo , Sarcoma de Ewing/diagnóstico , Sarcoma de Células Pequeñas/diagnóstico , Neoplasias Óseas/metabolismo , Recuento de Células , Condroblastoma/diagnóstico , Condroblastoma/metabolismo , Condrosarcoma/diagnóstico , Condrosarcoma/metabolismo , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Pronóstico , Estudios Retrospectivos , Sarcoma de Ewing/metabolismo , Sarcoma de Células Pequeñas/metabolismoRESUMEN
BACKGROUND: Osteosarcomas (OS) are aggressive neoplasms with a wide range of morphologic patterns. MATERIALS AND METHODS: OS cases (primary and xenotransplanted) with paraffin blocks available were collected and included in tissue microarrays (TMAs). A morphologic evaluation including the different passages in mice was carried out according to the new WHO criteria. In addition, TMAs were analyzed with a wide panel of immunohistochemical (IHC) markers (osteonectin, osteocalcin,cytokeratin, S100, Sox-9, Ki-67, Bcl-2, p53, p16, survivin, CD99, and caveolin-1). RESULTS: A total of 61 cases were collected. The distribution of the cases according to the histopathologic pattern was: 38 osteogenic OS, 8 primary chondrogenic OS, 2 primary telangiectatic OS, 6 parosteal OS, 2 primary small cell OS, 2 primary poorly differentiated OS, 1 primary dedifferentiated OS, and 3 primary pleomorphic MFH-like OS. The tumor morphology in xenotransplants was similar to the primary or metastatic tumor of origin and was generally maintained over the passages. The IHC results were heterogeneous and osteonectin and osteocalcin were the most expressed in original tumor and xenografts. S100 and Sox-9 were expressed in chondrogenic areas. Caveolin and survivin showed significant IHC variation between the subsequent passages. p16 displayed heterogenic expression. p53 expression increased over the passages, and Ki-67 expression was not associated with a more undifferentiated pattern, but increased over the passages. CONCLUSIONS: An accurate morphologic evaluation using TMAs in original tumor is essential for the OS diagnosis; hence there is no IHC marker that alone distinguishes the OS subtypes. Xenografts in OS allow the study of tumor progression in this type of aggressive neoplasm.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Osteosarcoma/metabolismo , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Estudios de Factibilidad , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Desnudos , Análisis por Micromatrices/métodos , Osteocalcina/metabolismo , Osteonectina/metabolismo , Osteosarcoma/patología , Trasplante HeterólogoRESUMEN
Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor that usually occurs in skin and retroperitoneum of infants and young children. We present a case of a newborn with a rapid tumor growth and a life-threatening Kasabach-Merritt syndrome with a progressive remission after treatment with vincristine and ticlopidine.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Trastornos de la Coagulación Sanguínea/complicaciones , Fibrinolíticos/administración & dosificación , Hemangioendotelioma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Ticlopidina/administración & dosificación , Vincristina/administración & dosificación , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Hemangioendotelioma/complicaciones , Humanos , Lactante , Masculino , Neoplasias Cutáneas/complicacionesRESUMEN
Unlike melanoma, clear cell sarcoma harbors either a t(12;22)(q13;q12) recurrent translocation, resulting in an EWSR1/ATF1 chimeric gene, or less commonly a t(2;22)(q34;q12) translocation fusing EWSR1 and CREB1. Few studies have examined the prevalence of all chimeric types and variants to assess the usage of ancillary genetic testing in routine diagnosis. We investigated rearrangement prevalence in 17 clear cell sarcomas, two positive control cell lines, and two melanomas (negative controls). Fluorescence in situ hybridization (FISH) analysis using the LSI EWSR1 break-apart probe and a reverse transcription polymerase chain reaction (RT-PCR) assay optimized for formalin-fixed paraffin-embedded tissue to detect all four reported EWSR1/ATF1 clear cell sarcoma chimeric types and the EWSR1/CREB1 variant was performed. All 15 cases available for testing by FISH were positive for EWSR1 rearrangement including two cases with insufficient RNA for RT-PCR. Thirteen of 15 cases successfully tested by RT-PCR harbored a type 1 chimeric transcript (EWSR1 exon 8/ATF1 exon 4), of which five tumors simultaneously carried a type 2 chimeric transcript (EWSR1 exon 7/ATF1 exon 5). One case carried a type 2 transcript alone and one case contained an EWSR1/CREB1 transcript. Both control cases were positive by both techniques with one case carrying both types 1 and 2 chimeric transcripts and the other types 2 and 3 (EWSR1 exon 10/ATF1 exon 5). Consequently, both techniques are equally effective in assessing for an EWSR1 rearrangement and are useful ancillary diagnostic tests for clear cell sarcoma. They also reinforce the prevalence of this translocation in these tumors. In addition, EWSR1-CREB1 was identified in a clear cell sarcoma of soft tissue providing further evidence that this chimeric variant is not exclusive to gastrointestinal clear cell sarcomas and should be included in RT-PCR assays of soft tissue clear cell sarcomas.
Asunto(s)
Proteína de Unión a CREB/genética , Proteínas de Unión a Calmodulina/genética , Proteínas de Fusión Oncogénica/genética , Proteínas de Unión al ARN/genética , Sarcoma de Células Claras/genética , Neoplasias de los Tejidos Blandos/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteína EWS de Unión a ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
A 52 year-old male patient diagnosed of ankylosing spondylitis presented with an iron deficiency anemia after a ten-month treatment of methotrexate. He did not respond to treatment with oral iron not a proton pump inhibitor and an upper endoscopy was performed. The histological study of the duodenal biopsies showed villus atrophy. After removing the methotrexate, administering intramuscular iron and undertaking a gluten-free diet, the histological and analytical alterations progressively resolved.
Asunto(s)
Antirreumáticos/efectos adversos , Enfermedad Celíaca/inducido químicamente , Metotrexato/efectos adversos , Antirreumáticos/uso terapéutico , Atrofia , Biopsia , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Duodeno/patología , Endoscopía Gastrointestinal , Humanos , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Espondilitis Anquilosante/tratamiento farmacológico , SíndromeRESUMEN
BACKGROUND: Chondrosarcoma (Chs) is the third most frequent primary malignant tumour of bone and can be primary or secondary, the latter results mainly from the malignant transformation of a benign pre-existing tumour. METHODS: All the cases diagnosed as Chs (primary tumours, recurrences and/or metastasis and xenotransplanted Chs) from the files of our Department were collected. Only cases with paraffin blocks available were selected (Total 32 cases). Six Tissue Microarrays (TMAs) were performed and all the cases and biopsies were distributed into the following groups: a) only paraffin block available from primary and/or metastatic tumours (3 TMAs), b) paraffin block available from primary and/or metastatic tumours as well as from the corresponding Nude mice xenotransplant (2 TMAs), c) only paraffin block available from xenotransplanted Chs (1 TMA). A reclassification of all the cases was performed; in addition, conventional hematoxylin-eosin as well as immunohistochemistry staining (S100, SOX-9, Ki-67, BCL-2, p53, p16, CK, CD99, Survivin and Caveolin) was analyzed in all the TMA. RESULTS: The distribution of the cases according to the histopathological pattern and the location of tumours were as follows: fourteen Grade I Chs (all primaries), two primary Grade II Chs, ten Grade III Chs (all primaries), five dedifferentiated Chs (four primaries and one primary with metastasis), and two Chs from cell cultures (Ch grade III). One recurrent extraskeletal myxoid Chs was included as a control in the TMA. Although there was heterogeneity in immunohistochemistry results of the different material analyzed, S100, SOX-9, Caveolin and Survivin were more expressed. The number of passages in xenotransplants fluctuated between 1 and 13. Curiously, in Grade I Chs, these implanted tumours hardly grew, and the number of passages did not exceed one. CONCLUSION: The study of Chs by means of TMA techniques is very important because it will improve the assessment of different antibodies applied in the immunohistochemical assays. Xenotransplanted tumours in TMA improve knowledge concerning the variability in the morphological pattern shown by these tumours during the evolution in nudes.
RESUMEN
BACKGROUND: Tissue microarrays (TMAs) are used to study genomics and proteomics in several tumour tissue samples. Cell lines (CC) are of great importance in the study of the genetic changes in tumours, and some reveal several aspects of tumour oncogenesis. There are few published reports on Ewing's tumours with TMAs including original tumours (OT) and corresponding CC. METHODS: We have performed four TMAs, from 3 OT and the corresponding CC of successive in vivo and in vitro tumour passages. Xenotransplant CC in nude mice from OT (XT/OT) was made. Subsequently multiple XT were performed and in vitro XT cell line (CC/XT) was obtained. In vivo re-inoculation of CC/XT (XT/CC) was planned. TMAs with the successive tumour passages that grew in nude mice (XT/OT and XT/CC) were analyzed by morphologic pattern (Hematoxilin/eosin), immunohistochemical staining (CD99, FLI1, p16, p53, ki-67), fluorescent in situ hybridization-FISH-(EWSR1 break apart, p16 and p53 status) and gene fusion types. RESULTS: Heterogeneous results of the p16, p53 and ki67 in OT, XT/OT, CC/XT and XT/CC were observed. The three cell lines revealed EWS/FLI1 rearrangements. p16 gene was deleted only in one case. The deletion was detected by FISH and confirmed by PCR assays. A p53 alteration was found in the second case with monosomy and subsequently polysomic status of chromosome 17 during the evolution of CC. The PCR study revealed p53 mutation. The third case showed hypermethylation in the promoter of p16. The growth of the tumour in nude mice was more accelerated when the inoculation was performed from the CC/XT, increasing progressively over the passages. The third case did not reveal tumour growth in nude mice after the re-inoculation of CC/XT. CONCLUSION: The study of several cores from original tumours and successive tumour passages in TMAs facilitated the analysis of the genetic alteration and protein expression in Ewing's tumours.
RESUMEN
Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumor characterized by a nodular growth pattern with eosinophilic cells usually in a reticular pattern and abundant myxoid stroma. In contrast to other myxoid sarcomas, the majority of extraskeletal myxoid chondrosarcomas harbor a balanced translocation, t(9;22)(q22;q12), that fuses EWSR1 with NR4A3 (also known as CHN). Other less common translocations involving NR4A3 have also been described. We examined the diagnostic utility of fluorescence in situ hybridization for extraskeletal myxoid chondrosarcoma using the LSI EWSR1 break-apart probe (Abbott Molecular/Vysis, Des Plaines, IL, USA). Sixteen cases of extraskeletal myxoid chondrosarcoma with formalin-fixed paraffin-embedded tissue available were retrieved (1991-2007). The mean age at time of presentation was 57 years (range, 30-78). The male to female ratio was 7:1. All cases where either consistent with or highly suggestive of the diagnosis, with most of the primary tumors occurring in the thigh, inguinal or gluteal region. Fifteen of 16 cases were analyzable, of which 14 (93%) were positive for the rearrangement of the EWSR1 locus. In this study, the vast majority of extraskeletal myxoid chondrosarcomas are associated with a rearrangement at the EWSR1 locus (22q12). Fluorescence in situ hybridization is useful to support the diagnosis of extraskeletal myxoid chondrosarcomas and may help to differentiate it from mimics such as other myxoid sarcomas, particularly in limited biopsies.
Asunto(s)
Proteínas de Unión a Calmodulina/genética , Condrosarcoma/diagnóstico , Proteínas de Unión al ARN/genética , Neoplasias de los Tejidos Blandos/diagnóstico , Adulto , Anciano , Condrosarcoma/genética , Condrosarcoma/secundario , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 9 , ADN de Neoplasias/genética , Diagnóstico Diferencial , Extremidades , Femenino , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Proteína EWS de Unión a ARN , Sarcoma/diagnóstico , Neoplasias de los Tejidos Blandos/genética , Translocación GenéticaRESUMEN
Liver pseudocysts are a very rare complication in acute pancreatitis with only a few cases previously described. The lack of experience and literature on this condition leads to difficulties in the differential diagnosis and management. We report herein a case of acute pancreatitis who developed multiple intrahepatic pseudocysts. After complete imaging evaluation, the diagnosis was still unclear and the patient was operated on. The presence of liver lesions in patients with acute pancreatitis should raise the possibility of intrahepatic pseudocysts.
Asunto(s)
Quistes/diagnóstico , Hepatopatías/diagnóstico , Pancreatitis/complicaciones , Enfermedad Aguda , Anciano , Quistes/etiología , Quistes/cirugía , Diagnóstico Diferencial , Humanos , Hepatopatías/etiología , Hepatopatías/cirugía , Imagen por Resonancia Magnética , Masculino , Pancreatitis/patología , Pancreatitis/cirugía , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: We aimed to evaluate the expression of the human anterior gradient-2 (AGR2) in breast cancer on RNA and protein level and to correlate it with clinicopathologic data, including patient survival. EXPERIMENTAL DESIGN: AGR2 mRNA expression was assessed by reverse transcription-PCR in 25 breast cancer samples and normal tissues. A polyclonal rabbit AGR antiserum was used for immunohistochemistry on 155 clinicopathologically characterized cases. Statistical analyses were applied to test for prognostic and diagnostic associations. RESULTS: Immunohistochemical detection of AGR2 was statistically significantly associated with positive estrogen receptor status and lower tumor grade. AGR2-positive tumors showed significantly longer overall survival times in univariate analyses. For the subgroup of nodal-negative tumors, an independent prognostic value of AGR2 was found. CONCLUSIONS: The expression of AGR2 in breast cancer is strongly associated with markers of tumor differentiation (estrogen receptor positivity, lower tumor grade). A prognostic effect of AGR2 for overall survival could be shown, which became independently significant for the group of nodal-negative tumors.
Asunto(s)
Neoplasias de la Mama/patología , Regulación Neoplásica de la Expresión Génica , Proteínas/genética , Mama/química , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mucoproteínas , Análisis Multivariante , Invasividad Neoplásica , Proteínas Oncogénicas , Pronóstico , Proteínas/análisis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de SupervivenciaRESUMEN
PURPOSE: CD24 is expressed in hematological malignancies as well as in a large variety of solid tumors including breast cancer. We aimed to evaluate CD24 protein expression in breast cancer and to correlate to clinicopathological data including patient survival. EXPERIMENTAL DESIGN: Primary breast carcinomas (201) with a mean clinical follow-up time of 53 months were immunostained using a monoclonal CD24 antibody (Ab-2, clone 24C02). The staining was evaluated as negative versus positive for statistical analysis. RESULTS: In invasive breast carcinomas, CD24 expression was observed in 84.6% of cases. In univariate survival analyses, a significant association of CD24 expression with shortened patient overall survival (5-year survival rate 91.9% versus 83.8%; P = 0.031; log rank test) and disease-free survival (5-year progression rate 88.3% versus 57.0%; P = 0.0008) was demonstrated. In multivariate analyses CD24, tumor grading and nodal status were significant prognostic parameters for shortened disease-free survival. CONCLUSIONS: Our data suggest that CD24 expression in primary breast cancer as detected by immunohistochemistry might be a new marker for a more aggressive breast cancer biology.