Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.
Background: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Methods: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference’s nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area…
Prognostic Impact of let-7e MicroRNA and Its Target Genes in Localized High-Risk Intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study
MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were co…
Chemokine Expression Is Involved in the Vascular Neogenesis of Ewing Sarcoma: A Preliminary Analysis of the Early Stages of Angiogenesis in a Xenograft Model.
Background Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). Methods The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm–4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymi…
A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole
Abstract Background Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. Methods We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in…
A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types
The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC)
CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study
A translational study was designed to analyze the expression of nucleotide excision repair (NER) and homologous recombination (HR) genes as potential predictive biomarkers for trabectedin in soft-tissue sarcoma (STS). This study is part of a randomized phase II trial comparing trabectedin plus doxorubicin versus doxorubicin in advanced STS. Gene expression levels were evaluated by qRT-PCR, while CUL4A protein levels were quantified by immunohistochemistry. Expression levels were correlated with patients&rsquo
PCA3 como biomarcador de segunda línea en un programa de screening oportunista prospectivo, aleatorizado y controlado
Resumen Objetivos Determinar el comportamiento del PCA3 como un marcador de segunda linea en un programa de cribado oportunista de cancer de prostata (CaP) y su comparacion con la calculadora de riesgo 3 del cribado aleatorizado europeo en cancer de prostata (ERSPC RC-3). Material y metodos Un total de 5.199 hombres de 40-75 anos se hicieron la prueba del antigeno prostatico especifico (PSA) y un tacto rectal (TR). Aquellos con TR normal y PSA ≥ 3 ng/ml se realizaron un PCA3. Todos los hombres con PCA3 ≥ 35 se hicieron biopsia inicial (BxI) —12 cilindros—. Aquellos con PCA3 Resultados PCA3 se testo en 838 hombres (16,1%). En los grupos PCA3(+) y PCA3(–), las tasas de deteccion global de CaP…
Identification of miR-187 and miR-182 as biomarkers of early diagnosis and prognosis in patients with prostate cancer treated with radical prostatectomy.
Purpose: miRNAs are noncoding RNAs that negatively regulate target mRNA gene expression. Aberrant miRNA expression is associated with prostate cancer pathogenesis. We identified miRNAs as potential biomarkers for prostate cancer diagnosis and prognosis. Materials and Methods: Total RNA was obtained from 10 normal prostate and 50 prostate cancer samples, and analyzed using the GeneChip (R) miRNA 2.0 Array. At a median followup of 92 months (range 2 to 189) an independent cohort of 273 paraffin embedded prostate cancer samples was used for validation by quantitative reverse transcriptase-polymerase chain reaction. Another 92 urine samples from patients undergoing prostate biopsy were evaluate…
MamaPred: A new and innovative approach to determine recurrence risk in HR+/HER2- early-stage breast cancer using HTG EdgeSeq technology.
558 Background: Genomic platforms, such as Mammaprint (Agendia) (MP) and OncoType (Genomic Health) (OT), have been validated to determine the risk of relapse in therapeutic decision-making in early-stage hormone receptor positive (HR+), epidermal growth factor receptor 2 (HER2) negative breast cancer (BC). Discordances in risk allocation between these platforms affect up to 30% of patients. This study aims to develop the MamaPred test to improve the diagnostic performance of recurrence risk in HR+/HER2- early-stage BC. Methods: A total of 606 HR+/HER2- early-stage BC previously tested with OT [n = 287; Low Risk (LR) = 165, Intermediate Risk (IR) = 103 and High Risk (HR) = 19] and MP (n = 3…
Optimización de un programa de cribado oportunista de cáncer de próstata; ensayo aleatorizado prospectivo del papel del PSA y del PCA3 en uso secuencial
Resumen Objetivos Reducir el numero de biopsias (Bx) innecesarias en un programa de cribado oportunista en cancer de prostata (CaP). Material y metodos Estudio prospectivo y aleatorizado evaluando el PCA3 como biomarcador de segunda linea. De septiembre de 2010 a septiembre de 2012 2.366 hombres con edad en rango 40-74 anos, y mas de 10 anos de expectativa de vida, fueron estudiados mediante PSA y tacto rectal (TR), excluyendo los biopsiados previamente o con infeccion urinaria reciente. Ante un TR sospechoso y/o PSA > 3 ng/ml se les realizo un PCA3. A todos aquellos con PCA3 ≥ 35 se les realizo una Bx inicial (IBx) —12 cilindros—. Con PCA3 0,5 ng/ml a 6 meses o PSAv > 0,75 ng/ml/ano. Res…
Optimizing prostate cancer screening; prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program
Abstract Objectives To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. Material and methods We performed a prospective evaluation of PCA3 as a second-line biomarker in an opportunistic screening for prostate cancer (PCa). From September 2010 until September 2012, 2,366 men, aged 40–74 years and with >10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA > 3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) —12cores—. Men with PCA3 .5 ng/ml at 4-6months or PSAv > .75 ng/…
Prognostic impact of COL5A2 and ACVR1B genes in intestinal high risk localized GIST. A Spanish Group for Research on Sarcoma (GEIS) study.
e22514Background: Molecular prognostic factors related to recurrence in localized GIST are still scarce so that this recurrence risk relies on clinical and pathologic factors as mitotic count, size...
Molecular diagnosis of dermatofibrosarcoma protuberans: A comparison between reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization methodologies
Dermatofibrosarcoma protuberans (DFSP) is characterized by the presence of the t(17;22)(q22;q13) that leads to the fusion of the COL1A1 and PDGFB genes. This translocation can be detected by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) techniques. We have evaluated the usefulness of a dual color dual fusion FISH probe strategy for COL1A1/PDGFB detection in a series of 103 archival DFSPs and compared the obtained results with RT-PCR analyses. FISH and RT-PCR were carried out on paraffin embedded tissue samples. Regarding the RT-PCR approach, all COL1A1 exons and exon 2 of PDGFB were evaluated. Sensitivity, specificity, positi…
Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial
[Background] Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here.
PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme
Objectives: PCA3 performance as a single second line biomarker is compared to the European Randomised Study of Screening for Prostate Cancer risk calculator model 3 (ERSPC RC-3) in an opportunistic screening in prostate cancer (PCa). Material and methods: 5,199 men, aged 40-75y, underwent prostate-specific antigen (PSA) screening and digital rectal examination (DRE). Men with a normal DRE and PSA >= 3 ng/ml had a PCA3 test done. All men with PCA3 >= 35 underwent an initial biopsy (IBx) 12 cores. Men with PCA3 = 3 ng/ml and DRE is normal, IBx could be avoided in 12.5% less than if ERSPC RC-3 is used and would reduce the false negative cases by 36.2%. At a FU of 21.7 months, this dual protoco…