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Accueil Nota Bene Cancer V2 Numéro 125 du 28 Février 2012 Dépistage, diagnostic et pronostic

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Nota Bene Cancer Numéro 125 du 28 Février 2012 RSS

Dépistage, diagnostic et pronostic

Découverte de technologies et de biomarqueurs

Menée sur 72 échantillons thyroïdiens prélevés par aspiration à l'aiguille fine, cette étude suggère qu'un modèle basé sur l'expression de quatre micro-ARNs permet de distinguer une lésion bénigne d'une lésion maligne de la thyroïde

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    Menée sur 72 échantillons thyroïdiens prélevés par aspiration à l'aiguille fine, cette étude suggère qu'un modèle basé sur l'expression de quatre micro-ARNs permet de distinguer une lésion bénigne d'une lésion maligne de la thyroïde

    “A Panel of four MicroRNAs accurately differentiates Malignant from Benign Indeterminate Thyroid Lesions on Fine Needle Aspiration”

    • Keutgen, Xavier M.;Filicori, Filippo;Crowley, Michael J.;Wang, Yongchun;Scognamiglio, Theresa;Hoda, Rana;Buitrago, Daniel;Cooper, David;Zeiger, Martha A.;Zarnegar, Rasa;Elemento, Olivier;Fahey, Thomas J.

    Purpose: Indeterminate thyroid lesions on Fine Needle Aspiration (FNA) harbor malignancy in about 25% of cases. Hemi- or total thyroidectomy has therefore been routinely advocated for definitive diagnosis. In this study we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathological diagnosis. Experimental Design: A predictive model was derived using 29 ex-vivo indeterminate thyroid lesions on FNA to differentiate benign from malignant tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in-vivo FNA samples. Expression levels of miR-222, miR-328, miR-197, miR-21, mir-181a and mir-146b were determined using RT-PCR. A statistical model was developed using the Support Vector Machine (SVM) approach. Results: A SVM model with 4 miRNAs (miR-222, miR-328, miR-197 and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent ...


Mots clés : Thyroïde; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée sur des échantillons de plasma prélevés jusqu'à 74 semaines avant le diagnostic d'un cancer du sein ER+ chez 420 patientes, cette étude identifie la présence de protéines du métabolisme glycolytique

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    Menée sur des échantillons de plasma prélevés jusqu'à 74 semaines avant le diagnostic d'un cancer du sein ER+ chez 420 patientes, cette étude identifie la présence de protéines du métabolisme glycolytique

    “Concordant release of glycolysis proteins into the plasma preceding a diagnosis of ER+ breast cancer”

    • Amon, Lynn M;Pitteri, Sharon J.;Li, Christopher I;McIntosh, Martin W;Ladd, Jon;Disis, Mary L;Porter, Peggy L;Wong, Chee-Hong;Zhang, Qing;Prentice, Ross L.;Lampe, Paul D.;Hanash, Samir M.

    Although the identification of peripheral blood biomarkers would enhance early detection strategies for breast cancer, the discovery of protein markers has been challenging. In this study, we sought to identify coordinated changes in plasma proteins associated with breast cancer based on large scale quantitative mass spectrometry. We analyzed plasma samples collected up to 74 weeks prior to diagnosis from 420 ER+ cases and matched controls enrolled in the Women's Health Initiative cohort. A gene set enrichment analysis was applied to 467 quantified proteins linking their corresponding genes to particular biological pathways. Based upon differences in the concentration of individual proteins, glycolysis pathway proteins exhibited a statistically significant difference between cases and controls. In particular, the enrichment was observed among cases in which blood was drawn closer to diagnosis (effect size for the 0-38 weeks pre-diagnostic group: 1.91; p-value:8.3E-05). Analysis of ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

A partir d'échantillons tumoraux prélevés sur des patients atteints d'un ostéosarcome, cette étude identifie une signature moléculaire, basée sur l'expression de plusieurs micro-ARNs, susceptible de servir de biomarqueur prédictif de la survenue de métastases et de la réponse thérapeutique

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    A partir d'échantillons tumoraux prélevés sur des patients atteints d'un ostéosarcome, cette étude identifie une signature moléculaire, basée sur l'expression de plusieurs micro-ARNs, susceptible de servir de biomarqueur prédictif de la survenue de métastases et de la réponse thérapeutique

    “MicroRNA signatures associate with pathogenesis and progression of osteosarcoma”

    • Jones, Kevin B.;Salah, Zaidoun;Del Mare, Sara;Galasso, Marco;Gaudio, Eugenio;Nuovo, Gerard J.;Lovat, Francesca;LeBlanc, Kimberly;Palatini, Jeff;Randall, R. Lor;Volinia, Stefano;Stein, Gary S.;Croce, Carlo M.;Lian, Jane B.;Aqeilan, Rami I.

    Osteosarcoma remains a leading cause of cancer death in adolescents, with no recent improvements in treatment or survival. Driving the lack of therapeutic inroads, the molecular etiology of osteosarcoma remains elusive. MicroRNAs (miRNAs) have demonstrated far-reaching effects on the cellular biology of development and cancer, but remain largely unexplored in osteosarcomagenesis. Here, we identify for the first time an miRNA signature reflecting the pathogenesis of osteosarcoma from surgically procured human specimens. The signature includes high expression of miR-181a, miR-181b, and miR-181c as well as reduced expression of miR-16, miR-29b, and miR-142-5p. We also demonstrate that miR-181b and miR-29b exhibit restricted expression to distinct cell populations in the tumor tissue. Further, higher expression of miR-27a and miR-181c* in pre-treatment biopsy samples characterized patients who developed clinical metastatic disease. In addition, higher expression of miR-451 and miR-15b in ...


Mots clés : Sarcome; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée à l'aide d'un modèle murin et d'échantillons de sérum prélevés sur des patients présentant des adénomes du côlon-rectum, cette étude suggère que le niveau sérique de la protéine CHI3L1 pourrait être utile pour la détection précoce d'une lésion précancéreuse

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    Menée à l'aide d'un modèle murin et d'échantillons de sérum prélevés sur des patients présentant des adénomes du côlon-rectum, cette étude suggère que le niveau sérique de la protéine CHI3L1 pourrait être utile pour la détection précoce d'une lésion précancéreuse

    “Proximal fluid proteome profiling of mouse colon tumors reveals biomarkers for early diagnosis of human colorectal cancer”

    • Fijneman, Remond J.A.;de Wit, Meike;Pourghiasian, Maral;Piersma, Sander R.;Pham, Thang V.;Warmoes, Marc O.;Lavaei, Mehrdad;Piso, Chloe;Smit, Fiona;Delis - van Diemen, Pien M.;van Turenhout, Sietze T.;Terhaar sive Droste, Jochim S.;Mulder, Chris J.J.;Blankenstein, Marinus A.;Robanus-Maandag, Els C.;Smits, Ron;Fodde, Riccardo;van Hinsbergh, Victor W.M.;Meijer, Gerrit A.;Jimenez, Connie R.

    Purpose: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for early diagnosis of CRC. Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. The FabplCre;Apc15lox/+ mouse model represents early stage development of human sporadic CRC. Proximal fluids were collected from normal colon and colon tumors and subjected to in-depth proteome profiling using tandem mass spectrometry. CEA and CHI3L1 human serum protein levels were determined by ELISA. Results: Out of 2172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (p<0.05) and abundantly (>5-fold) more excreted by tumors than by controls. Further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates among which S100A9, MCM4, and four other proteins ...


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée sur des échantillons tumoraux prélevés sur 151 patients atteints d'un carcinome urothélial des voies urinaires supérieures et à l'aide d'un modèle murin, cette étude suggère que l'expression du gène KiSS-1 pourrait servir de biomarqueur prédictif de la survenue de métastases et évalue l'intérêt de la métastatine en prévention du processus métastatique

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    Menée sur des échantillons tumoraux prélevés sur 151 patients atteints d'un carcinome urothélial des voies urinaires supérieures et à l'aide d'un modèle murin, cette étude suggère que l'expression du gène KiSS-1 pourrait servir de biomarqueur prédictif de la survenue de métastases et évalue l'intérêt de la métastatine en prévention du processus métastatique

    “Prognostic role of KiSS-1 and possibility of therapeutic modality of metastin, the final peptide of the KiSS-1 gene, in urothelial carcinoma”

    • Takeda, Toshikazu;Kikuchi, Eiji;Mikami, Shuji;Suzuki, Eriko;Matsumoto, Kazuhiro;Miyajima, Akira;Okada, Yasunori;Oya, Mototsugu

    The KiSS-1 gene has been reported to be a metastasis suppressor gene in human melanoma. The gene product was isolated from human placenta as the ligand of GPR54, a G protein-coupled receptor, and the C-terminally amidated peptide of 54 amino acids is called metastin. The binding of metastin to GPR54 has been shown to inhibit tumor metastasis in some tumor cells, however, its function remains unclear in urothelial carcinoma (UC). We first evaluated KiSS-1 expression and GPR54 expression in 151 patients with upper urinary tract UC (UTUC) to determine their prognostic significance. Next, we examined the role of metastin in the invasiveness and lung metastasis of MBT-2 variant (MBT-2V), which is a highly metastatic murine bladder cancer cell. Multivariate analysis revealed that KiSS-1 expression was an independent predictor of metastasis and overall survival. However, GPR54 expression was not selected. Hematogeneous metastasis had a significantly lower level of KiSS-1 expression compared ...


Mots clés : Appareil urinaire (autre); Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Menée sur un modèle murin, cette étude évalue la faisabilité d'une technique d'imagerie in vivo des tumeurs mettant en oeuvre des sondes fluorescentes à base d'ARNs interférents

  • In-vivo tumor imaging using a novel RNAi-based detection mechanism
    Nanomedicine : nanotechnology, biology, and medicine, sous presse, 2012 (résumé)
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    Menée sur un modèle murin, cette étude évalue la faisabilité d'une technique d'imagerie in vivo des tumeurs mettant en oeuvre des sondes fluorescentes à base d'ARNs interférents

    “In-vivo tumor imaging using a novel RNAi-based detection mechanism”

    • Wan, Kayiu;Ebert, Bernd;Voigt, Jan;Wang, Qing;Dai, Yiyang;Haag, Rainer;Kemmner, Wolfgang

    A new concept of tumor imaging is introduced using a siRNA-based probe that is capable of amplifying a specific endogenous fluorescence emission within cancerous tissue. In previous studies, we have demonstrated a significant down regulation of Ferrochelatase (FECH) mRNA-expression in colorectal carcinomas leading to the accumulation of protoporphyrin IX (PpIX), a fluorescent metabolite of the heme synthesis. Here, we report on first in-vivo experiments in xenografted nude mice using folate-coupled liposomes or dendritic polyglycerolamine nanoparticles carrying ferrochelatase-siRNA in order to enhance PpIX-derived fluorescence within the tumor tissue. Tiny tumor foci could be monitored by the emission of PpIX fluorescence in vivo. Due to the omnipresence of the heme synthesis pathway, targeted application of ferrochelatase-siRNA may provide a general means for molecular imaging.


Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Découverte de technologies et de biomarqueurs)

Evaluation des technologies et des biomarqueurs

Menée sur 1 997 femmes âgées de 40 à 49 ans et ayant été diagnostiquées avec un cancer du sein entre 1990 et 2008, cette étude analyse l'évolution des méthodes de détection du cancer et évalue notamment l'effet de la mammographie sur le stade au diagnostic

  • Impact of Mammography Detection on the Course of Breast Cancer in Women Aged 40–49 Years
    Radiology, Vol. 262 (3), pp. 797-806, 2012 (résumé)
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    Menée sur 1 997 femmes âgées de 40 à 49 ans et ayant été diagnostiquées avec un cancer du sein entre 1990 et 2008, cette étude analyse l'évolution des méthodes de détection du cancer et évalue notamment l'effet de la mammographie sur le stade au diagnostic

    “Impact of Mammography Detection on the Course of Breast Cancer in Women Aged 40–49 Years”

    • Malmgren, Judith A.;Parikh, Jay;Atwood, Mary K.;Kaplan, Henry G.

    Purpose: To analyze trends in detection method related to breast cancer stage at diagnosis, treatments, and outcomes over time among 40–49-year-old women.Materials and Methods: i This study was institutional review board approved, with a waiver of informed consent, and HIPAA compliant. A longitudinal prospective cohort study was conducted of women aged 40–49 years who had primary breast cancer, during 1990–2008, and were identified and tracked by a dedicated registry database (n = 1977). Method of detection—patient detected (PtD), physician detected (PhysD), or mammography detected (MamD)—was chart abstracted. Disease-specific survival and relapse-free survival statistics were calculated by using the Kaplan-Meier method for stage I–IV breast cancer.Results: A significant increase in the percentage of MamD breast cancer over time (28%–58%) and a concurrent decline in patient and physician detected (Pt/PhysD) breast cancer (73%–42%) (Pearson x2 = 72.72, P < .001) were ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur 349 échantillons prélevés par biopsie à l'aiguille sur des patients atteints d'un cancer de la prostate, cette étude évalue l'association entre un indicateur basé sur les niveaux d'expression de 31 gènes et la mortalité par cancer de la prostate

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    Menée sur 349 échantillons prélevés par biopsie à l'aiguille sur des patients atteints d'un cancer de la prostate, cette étude évalue l'association entre un indicateur basé sur les niveaux d'expression de 31 gènes et la mortalité par cancer de la prostate

    “Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort”

    • Cuzick, J.;Berney, D. M.;Fisher, G.;Mesher, D.;Moller, H.;Reid, J. E.;Perry, M.;Park, J.;Younus, A.;Gutin, A.;Foster, C. S.;Scardino, P.;Lanchbury, J. S.;Stone, S.

    Background: The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy. Methods: Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer. Results: n univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10−9) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for ...


Mots clés : Prostate; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Cet article passe en revue les travaux récents sur le développement de signatures moléculaires dans le cancer du poumon

  • Molecular Signatures of Lung Cancer: Defining New Diagnostic and Therapeutic Paradigms
    Molecular Diagnosis & Therapy, Vol. 16 (1), pp. 1-6, 2012 (résumé)
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    Cet article passe en revue les travaux récents sur le développement de signatures moléculaires dans le cancer du poumon

    “Molecular Signatures of Lung Cancer: Defining New Diagnostic and Therapeutic Paradigms”

    • Balko, Justin M.;Arteaga, Carlos L.

    Molecular profiling holds great promise for improving our ability to diagnose, prognosticate, and select individualized treatments for lung cancer patients. However, using multidimensional data and novel technologies to derive these profiles is limited by our ability to employ the assay in a clinical scenario where it can impact the course of disease. Although many molecular signatures have been reported in lung cancer, as of yet, few have been sufficiently validated for widespread clinical use. Recently, several novel signatures have been reported, which address critical aspects of patient care and/or demonstrate improved efforts for appropriate clinical validation. Here, we present our opinion on the current state of the field of molecular signatures in lung cancer.


Mots clés : Poumon; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur des échantillons tumoraux prélevés sur 1 170 patients atteints d'un cancer colorectal, cette étude évalue l'association entre la présence d'une mutation sur l'exon 9 ou l'exon 20 du gène PI3KCA et la survie des patients

  • Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review
    Clinical Cancer Research, sous presse, 2012 (résumé)
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    Menée sur des échantillons tumoraux prélevés sur 1 170 patients atteints d'un cancer colorectal, cette étude évalue l'association entre la présence d'une mutation sur l'exon 9 ou l'exon 20 du gène PI3KCA et la survie des patients

    “Prognostic Role of PIK3CA Mutation in Colorectal Cancer: Cohort Study and Literature Review”

    • Liao, Xiaoyun;Morikawa, Teppei;Lochhead, Paul;Imamura, Yu;Kuchiba, Aya;Yamauchi, Mai;Nosho, Katsuhiko;Qian, Zhi Rong;Nishihara, Reiko;Meyerhardt, Jeffrey;Fuchs, Charles S;Ogino, Shuji

    Purpose: Mutations in PIK3CA (the gene encoding the p110alpha; catalytic subunit of phosphatidylinositide-3-kinase, PI3K) play an important role in colorectal carcinogenesis. Experimental evidence suggests that PIK3CA exon 9 and exon 20 mutations trigger different biological effects, and that concomitant mutations in both exons 9 and 20 synergistically enhance tumorigenic effects. Thus, we hypothesized that PIK3CA exon 9 and exon 20 mutations might have differential effects on clinical outcome in colorectal cancer, and that concomitant PIK3CA exon 9 and 20 mutations might confer aggressive tumor behavior. Experimental Design: We sequenced PIK3CA by pyrosequencing in 1170 rectal and colon cancers in two prospective cohort studies, and found 189 (16%) PIK3CA-mutated tumors. Mortality hazard ratio (HR) according to PIK3CA status was computed using Cox proportional hazards model, adjusting for clinical and molecular features including microsatellite instability, CpG island methylator ...


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Menée sur des échantillons prélevés sur 74 patients présentant des polypes hyperplasiques, cette étude française évalue l'intérêt de la mesure du niveau d'expression de la progastrine pour prédire le développement de polypes adénomateux

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    Menée sur des échantillons prélevés sur 74 patients présentant des polypes hyperplasiques, cette étude française évalue l'intérêt de la mesure du niveau d'expression de la progastrine pour prédire le développement de polypes adénomateux

    “A new biomarker that predicts colonic neoplasia outcome in patients with hyperplastic colonic polyps”

    • Do, Catherine;Bertrand, Claudine;Palasse, Julien;Delisle, Marie-Bernadette;Shulkes, Arthur;Cohen-Jonathan Moyal, Elizabeth L.;Ferrand, Audrey;Seva, Catherine

    The most frequently occurring lesions in the colon are the hyperplastic polyps (HP). HP have long been considered as lesions with no malignant potential and colonoscopy for these patients is not recommended. However recent works suggest that HP may represent precursor lesions of some sporadic colorectal cancers. Until now, none biomarker allows to identify the subset of HP that may have a malignant potential. Because the hormone precursor, progastrin has been involved in colon carcinogenesis, we investigated whether its expression in HP predicts occurrence of colonic neoplasm after resection of HP. We retrospectively analyzed progastrin expression in HP from 74 patients without history of colorectal pathology. In our study, 41% of patients presenting an initial HP subsequently developed adenomatous polyps, recognized as precursor lesions for colorectal adenocarcinomas. Progastrin was overexpressed in the HP in 40% of the patients. We showed a significant association between progastrin ...


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Evaluation des technologies et des biomarqueurs)

Essais de technologies et de biomarqueurs dans un contexte clinique

Menée à partir d'échantillons tumoraux prélevés sur 193 patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude montre une association entre le niveau d'expression tumorale des récepteurs EGFR et EGFR PY1068 et la survie des patients

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    Menée à partir d'échantillons tumoraux prélevés sur 193 patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude montre une association entre le niveau d'expression tumorale des récepteurs EGFR et EGFR PY1068 et la survie des patients

    “Tumor epidermal growth factor receptor (EGFR) and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma”

    • Wheeler, Sarah E;Siwak, Doris R;Chai, Raymond L;LaValle, Courtney R;Seethala, Raja R;Wang, Lin;Cieply, Kathleen M.;Sherer, Carol;Joy, Corwin;Mills, Gordon B.;Argiris, Athanassios;Siegfried, Jill M.;Grandis, Jennifer R.;Egloff, Ann Marie

    Purpose:To assess the prognostic value of EGFR molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients and Methods: HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N=154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N=39) were evaluated for EGFR gene amplification by fluorescence in situ hybridization (FISH) and EGFR protein by immunohistochemical (IHC) staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (RPPA) (n=67). Tumor (n=50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR. Results:EGFR expression by IHC was significantly higher in the EDRN tumors with EGFR gene amplification (P<0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and ...


Mots clés : Voies aérodigestives supérieures; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée de 1999 à 2007 sur 549 femmes présentant des lésions mammaires, cette étude compare la sensibilité, la spécicificité et la valeur prédictive d'une mammographie et d'une échographie en fonction de l'âge et du statut ménopausique des patientes

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    Menée de 1999 à 2007 sur 549 femmes présentant des lésions mammaires, cette étude compare la sensibilité, la spécicificité et la valeur prédictive d'une mammographie et d'une échographie en fonction de l'âge et du statut ménopausique des patientes

    “A Comparison of Mammography and Ultrasound in Women with Breast Disease: A Receiver Operating Characteristic Analysis”

    • Ying, Xuexiang;Lin, Yanping;Xia, Xiaotian;Hu, Bin;Zhu, Zhuhua;He, Pingqing

    Abstract: The purpose of this study was to compare mammography and sonography, as well as their combination, for detecting breast tumors in symptomatic patients. The effects of age and hormonal status were also examined. From 1999 to 2007, 549 patients underwent 665 examination sessions (mammography and ultrasound). Abnormalities were deemed positive if biopsy findings revealed malignancy and negative if findings from biopsy or all screening examinations were negative. On pathology, 246 lesions were malignant and 419 were benign in the 549 patients. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of mammography and sonography were 81.71% and 95.53%, 85.44% and 80.43%, 76.72% and 74.13%, 88.83% and 96.84%, and 0.886 and 0.948, respectively. The sensitivity and diagnostic accuracy among patients <50 years of age were significantly higher for sonography than for mammography ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 213 patientes atteintes d'un carcinome canalaire in situ du sein et traitées par chirurgie conservatrice, cette étude montre une association entre le niveau d'expression tumorale des gènes HER2/neu et Ki-67 et le risque de récidive

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    Menée sur 213 patientes atteintes d'un carcinome canalaire in situ du sein et traitées par chirurgie conservatrice, cette étude montre une association entre le niveau d'expression tumorale des gènes HER2/neu et Ki-67 et le risque de récidive

    “HER2/neu and Ki-67 expression predict non-invasive recurrence following breast-conserving therapy for ductal carcinoma in situ”

    • Rakovitch, E.;Nofech-Mozes, S.;Hanna, W.;Narod, S.;Thiruchelvam, D.;Saskin, R.;Spayne, J.;Taylor, C.;Paszat, L.

    Background : Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that may progress to invasive cancer. Identification of factors that predict recurrence and distinguish DCIS from invasive recurrence would facilitate treatment recommendations. We examined the prognostic value of nine molecular markers on the risks of local recurrence (DCIS and invasive) among women treated with breast-conserving therapy. Methods : A total of 213 women who were treated with breast-conserving therapy between 1982 and 2000 were included; 141 received breast-conserving surgery alone and 72 cases received radiotherapy. We performed immunohistochemical staining on the DCIS specimen for nine markers: oestrogen receptor, progesterone receptor, Ki-67, p53, p21, cyclinD1, HER2/neu, calgranulin and psoriasin. We performed univariable and multivariable survival analyses to identify markers associated with the recurrence. Results :The rate of recurrence at 10 years was 36% for patients treated ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 103 patientes atteintes d'un cancer du sein récemment diagnostiqué et de stade précoce, cette étude évalue l'intérêt d'une tomographie numérique préopératoire à émission de positrons pour déterminer le stade de la maladie

  • Preoperative PET/CT in early-stage breast cancer
    Annals of Oncology, sous presse, 2012 (résumé)
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    Menée sur 103 patientes atteintes d'un cancer du sein récemment diagnostiqué et de stade précoce, cette étude évalue l'intérêt d'une tomographie numérique préopératoire à émission de positrons pour déterminer le stade de la maladie

    “Preoperative PET/CT in early-stage breast cancer”

    • Bernsdorf, M.;Berthelsen, A. K.;Wielenga, V. T.;Kroman, N.;Teilum, D.;Binderup, T.;Tange, U. B.;Andersson, M.;Kjær, A.;Loft, A.;Graff, J.

    Background: The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer.Patients and methods: A total of 103 consecutive patients with newly diagnosed operable breast cancer with tumors ≥2 cm were independently examined preoperatively with conventional assessment (mammography, breast/axillary ultrasound, chest X-ray and blood samples) and PET/CT with no prior knowledge of the other.Results: PET/CT identified a primary tumor in all but three patients (97%). PET/CT solely detected distant metastases (ovary, bones and lung) in 6 patients and new primary cancers (ovary, lung) in another two patients, as well as 12 cases of extra-axillary lymph node involvement. In 15 patients (15%), extra-axillary malignancy was detected by PET/CT only, leading to an upgrade of initial staging in 14% (14/103) and ultimately a modification of ...


Mots clés : Sein; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Mené sur 53 302 participants âgés de 50 à 69 ans, cet essai randomisé contrôlé compare la sensibilité et la spécificité d'une coloscopie et d'un test immunochimique fécal pour détecter précocement un cancer colorectal

  • Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening
    New England Journal of Medicine, Vol. 366 (8), pp. 697-706, 2012 (résumé)
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    Mené sur 53 302 participants âgés de 50 à 69 ans, cet essai randomisé contrôlé compare la sensibilité et la spécificité d'une coloscopie et d'un test immunochimique fécal pour détecter précocement un cancer colorectal

    “Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening”

    • Quintero, Enrique;Castells, Antoni;Bujanda, Luis;Cubiella, Joaquín;Salas, Dolores;Lanas, Ángel;Andreu, Montserrat;Carballo, Fernando;Morillas, Juan Diego;Hernández, Cristina;Jover, Rodrigo;Montalvo, Isabel;Arenas, Juan;Laredo, Eva;Hernández, Vicent;Iglesias, Felipe;Cid, Estela;Zubizarreta, Raquel;Sala, Teresa;Ponce, Marta;Andrés, Mercedes;Teruel, Gloria;Peris, Antonio;Roncales, María-Pilar;Polo-Tomás, Mónica;Bessa, Xavier;Ferrer-Armengou, Olga;Grau, Jaume;Serradesanferm, Anna;Ono, Akiko;Cruzado, José;Pérez-Riquelme, Francisco;Alonso-Abreu, Inmaculada;de la Vega-Prieto, Mariola;Reyes-Melian, Juana Maria;Cacho, Guillermo;Díaz-Tasende, José;Herreros-de-Tejada, Alberto;Poves, Carmen;Santander, Cecilio;González-Navarro, Andrés

    Background : Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. Methods : In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. Results : The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were ...


  • Colonoscopy as a Triage Screening Test
    New England Journal of Medicine, Vol. 366 (8), pp. 759-760, 2012 (éditorial)
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    Mené sur 53 302 participants âgés de 50 à 69 ans, cet essai randomisé contrôlé compare la sensibilité et la spécificité d'une coloscopie et d'un test immunochimique fécal pour détecter précocement un cancer colorectal

    “Colonoscopy as a Triage Screening Test”

    • Bretthauer, Michael ; Kalager, Mette


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 312 patients atteints d'un cancer colorectal de stade I et II et ayant subi un traitement chirurgical, cette étude évalue l'association entre la présence de cellules tumorales au niveau des ganglions lymphatiques régionaux et le risque de récidive

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    Menée sur 312 patients atteints d'un cancer colorectal de stade I et II et ayant subi un traitement chirurgical, cette étude évalue l'association entre la présence de cellules tumorales au niveau des ganglions lymphatiques régionaux et le risque de récidive

    “Isolated Tumor Cells in Regional Lymph Nodes as Relapse Predictors in Stage I and II Colorectal Cancer”

    • Mescoli, Claudia;Albertoni, Laura;Pucciarelli, Salvatore;Giacomelli, Luciano;Russo, Valentina M.;Fassan, Matteo;Nitti, Donato;Rugge, Massimo

    Purpose Lymph node (LN) involvement is the most important prognostic factor in colorectal cancer (CRC), and pN-positive status identifies patients who require adjuvant chemotherapy. Approximately 15% to 20% of patients without nodal metastases (pN0) develop recurrent disease. In this study, we tested the prognostic significance of isolated tumor cells (ITCs) in LNs of patients with pN0 CRC (stages I and II).Patients and Methods ITCs in LNs regional to CRC were assessed in 312 consecutive patients with pN0 CRC who were followed up clinically and/or endoscopically for at least 6 months after surgery (mean, 67 months; median, 64 months; range, 8 to 102 months). LNs were dissected from gross surgical specimens according to a standardized protocol (with a mean of 17 LNs per patient; range, five to 107 LNs). In all, 5,313 pN0 LNs were collected and assessed by using cytokeratin immunostaining in two serial histology sections from each LN, which amounting to a total of 10,626 specimens. The ...


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Menée sur 374 patients atteints d'un mélanome uvéal traité par énucléation (durée médiane de suivi : 5,2 ans), cette étude évalue la valeur pronostique d'altérations du chromosome 3 détectées par l'analyse des microsatellites

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    Menée sur 374 patients atteints d'un mélanome uvéal traité par énucléation (durée médiane de suivi : 5,2 ans), cette étude évalue la valeur pronostique d'altérations du chromosome 3 détectées par l'analyse des microsatellites

    “Prognostic significance of chromosome 3 alterations determined by microsatellite analysis in uveal melanoma: a long-term follow-up study”

    • Thomas, S.;Putter, C.;Weber, S.;Bornfeld, N.;Lohmann, D. R.;Zeschnigk, M.

    Background : In uveal melanoma (UM), the most frequent primary intraocular tumour in adults, loss of one entire chromosome 3 (monosomy 3 (M3)) is observed in ~50% of tumours and is significantly associated with metastatic disease. The strong association of metastatic disease with M3 offers the opportunity for molecular prognostic testing of UM patients. Methods : To re-evaluate M3 as prognostic marker in our clinical and laboratory setting and to determine the metastatic potential of rare tumours with partial M3, we performed a comprehensive study on 374 UM patients treated by enucleation in our clinic within 10 consecutive years, starting in 1998. Genotyping of all tumours was performed by microsatellite analysis. Results : Median follow-up time was 5.2 years. The disease-specific mortality rates (death by UM metastases) for tumours with disomy 3 (D3) and M3 were 13.2% and 75.1%, respectively. The disease-specific survival was worse when M3 was observed together with chromosome 8 ...


Mots clés : Autres organes; Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Cette étude prospective évalue l'association entre une périodontite (12 605 cas), le niveau sérique d'anticorps anti Porphyromonas gingivalis ( 7 852 cas) et la mortalité par cancer des voies aéro-digestives supérieures et de l'appareil digestif (105 cas)

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    Cette étude prospective évalue l'association entre une périodontite (12 605 cas), le niveau sérique d'anticorps anti Porphyromonas gingivalis ( 7 852 cas) et la mortalité par cancer des voies aéro-digestives supérieures et de l'appareil digestif (105 cas)

    “Periodontal Disease, Porphyromonas Gingivalis (P. gingivalis) Serum Antibody Levels and Orodigestive Cancer Mortality”

    • Ahn, Jiyoung;Segers, Stephanie;Hayes, Richard B.

    Periodontitis, the progressive loss of the alveolar bone around the teeth and the major cause of tooth loss in adults, is due to oral microorganisms, including Porphyromonas gingivalis (P gingivalis). Periodontitis is associated with a local overly aggressive immune response and a spectrum of systemic effects, but the role of this condition in orodigestive cancers is unclear. We prospectively examined clinically ascertained periodontitis (N=12,605) and serum IgG immune response to P gingivalis (N=7,852) in relation to orodigestive cancer mortality among men and women in the National Health and Nutrition Examination Survey (NHANES III). A detailed oral health exam was conducted from 1988-1994 in survey Phases I and II, while serum IgG for P gingivalis was measured from 1991-1994 in Phase II only. One-hundred and five orodigestive cancer deaths were ascertained through December 31, 2006. Periodontitis (moderate or severe) was associated with increased orodigestive cancer mortality ...


Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Essais de technologies et de biomarqueurs dans un contexte clinique)

Politiques et programmes de dépistage

A partir d'une enquête auprès de 139 Centres de lutte contre le cancer aux Etats-Unis, cette étude évalue les pratiques de tests de détection d'un syndrome de Lynch et de suivi des résultats anormaux

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    A partir d'une enquête auprès de 139 Centres de lutte contre le cancer aux Etats-Unis, cette étude évalue les pratiques de tests de détection d'un syndrome de Lynch et de suivi des résultats anormaux

    “Reflex Immunohistochemistry and Microsatellite Instability Testing of Colorectal Tumors for Lynch Syndrome Among US Cancer Programs and Follow-Up of Abnormal Results”

    • Beamer, Laura C.;Grant, Marcia L.;Espenschied, Carin R.;Blazer, Kathleen R.;Hampel, Heather L.;Weitzel, Jeffrey N.;MacDonald, Deborah J.

    Purpose Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established tools to screen for Lynch syndrome (LS). Although many cancer centers have adopted these tools as reflex LS screening after a colorectal cancer diagnosis, the standard of care has not been established, and no formal studies have described this practice in the United States. The purpose of this study was to describe prevalent practices regarding IHC/MSI reflex testing for LS in the United States and the subsequent follow-up of abnormal results.Materials and Methods A 12-item survey was developed after interdisciplinary expert input. A letter of invitation, survey, and online-survey option were sent to a contact at each cancer program. A modified Dillman strategy was used to maximize the response rate. The sample included 39 National Cancer Institute–designated Comprehensive Cancer Centers (NCI-CCCs), 50 randomly selected American College of ...


  • Screening Patients With Colorectal Cancer for Lynch Syndrome: What Are We Waiting For?
    Journal of Clinical Oncology, sous presse, 2012 (éditorial en libre accès)
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    A partir d'une enquête auprès de 139 Centres de lutte contre le cancer aux Etats-Unis, cette étude évalue les pratiques de tests de détection d'un syndrome de Lynch et de suivi des résultats anormaux

    “Screening Patients With Colorectal Cancer for Lynch Syndrome: What Are We Waiting For?”

    • Kastrinos, Fay ; Syngal, Sapna


Mots clés : Colon-rectum; Dépistage, diagnostic et pronostic (Politiques et programmes de dépistage)

Ressources et infrastructures (Dépistage)

Cet article analyse la controverse sur les tests permettant de prédire la réponse à une chimiothérapie adjuvante dans le cancer du sein

  • Targeting Adjuvant Chemotherapy: A Good Idea That Needs to Be Proven!
    Journal of Clinical Oncology, sous presse, 2012 (article en libre accès)
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    Cet article analyse la controverse sur les tests permettant de prédire la réponse à une chimiothérapie adjuvante dans le cancer du sein

    “Targeting Adjuvant Chemotherapy: A Good Idea That Needs to Be Proven!”

    • Hayes, Daniel F.

    The success of adjuvant therapy in reducing recurrence and mortality has been established for endocrine therapy, chemotherapy, and more recently, trastuzumab. Indeed, Berry et al. have suggested that at least one half of the remarkable reduction in breast cancer mortality observed over the last 30 years can be attributed to widespread application of adjuvant systemic therapy. The Oxford Worldwide Overview of early breast cancer trials, conducted by the Early Breast Cancer Trialists Collaborative Group (EBCTG) demonstrated definitively that, without respect to subgrouping, chemotherapy appears to reduce breast cancer recurrence and mortality by approximately 30% and 20%, respectively. (...]


Mots clés : Sein; Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

Cet article passe en revue les risques associés à la vente directe de marqueurs tumoraux pour le dépistage des cancers

  • Risks of Online Direct-to-Consumer Tumor Markers for Cancer Screening
    Journal of Clinical Oncology, sous presse, 2012 (article en libre accès)
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    Cet article passe en revue les risques associés à la vente directe de marqueurs tumoraux pour le dépistage des cancers

    “Risks of Online Direct-to-Consumer Tumor Markers for Cancer Screening”

    • Lovett, Kimberly M.;Liang, Bryan A.;Mackey, Timothy K.

    Cancer is the leading cause of death worldwide. Given the emotional impact of a potential cancer diagnosis, patients often search for methods of early detection. Moreover, with a growing direct-to-consumer (DTC) industry advertising medical products online, patients are increasingly empowered to seek out cancer diagnoses and treatments without qualified medical guidance. Indeed, a 2005 National Cancer Institute survey found 50% of respondents would seek online cancerrelated information before physician consultation. Yet, problematically, studies have highlighted fraudulent claims made by online DTC medical product marketing as well as dangers associated with various disease-based DTC screening tests. These concerns have expanded to cancer. (...]


Mots clés : Cancer (général); Dépistage, diagnostic et pronostic (Ressources et infrastructures (Dépistage))

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