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The Massive Open Online Course (or MOOC) "Diagnostic Strategies Cancers", was hosted in autumn 2016 on the platform "France Universite Numerique" and had two levels of learners: students in the field of health and biology and the general public. Of the 5285 learners in 81 different countries, 1237 (23%) were successfully certified. This MOOC was also integrated into the teaching program of medical students of Paris Diderot University and Paris 13 University. Using anonymous questionnaires before and after MOOC, it has been shown that pathology is less known than other medical specialties. Participation in this MOOC led to a marked improvement in participants' knowledge of the place and role of the pathologist in the diagnosis of cancers. Regarding the students who have followed the MOOC as part of their university course, their comments were very positive, but it is necessary to make substantial adjustments in the amounts and contents of the campus-based courses.

We report the case of a 63-year-old healthy patient who was admitted for surgery of a suprasellar tumor with extension to the optic chiasm responsible of visual disturbance. Histopathological examination revealed a tumoral proliferation composed of epithelioid cells without atypia arranged in cords in a mucinous matrix surrounded by some lymphocytic inflammatory infiltrates. On immunohistochemistry, the neoplastic cells strongly expressed GFAP and CD34, a weak expression of EMA, an expression of TTF1 without immunoreactivity for brachyury. Ki-67 labeling index was low around 1%. The diagnosis of chordoid glioma was made. Surprisingly, tumor cells expressed IDH1R132H but molecular analysis did not reveal any mutation of IDH1/2 genes. There was no expression of p53 but high overexpression of EGFR. Chordoid glioma is a rare and low-grade entity. The precise histogenesis remains debated. Our case is unusual because of the infiltration of the optic chiasm and because of the immunoexpression of IDH1R132H without underlying mutations of IDH1/2 genes.

Resume Le cours en ligne ouvert et massif (Massive Open Online Course ou MOOC) est une nouvelle modalite pedagogique en ligne s’adressant a une audience dont la taille est sans precedent par rapport aux autres strategies d’enseignement tout en permettant des interactions avec une equipe pedagogique. Ces cours universitaires, le plus souvent encore gratuits, donnent lieu a la remise d’une attestation de suivi et pourraient rapidement etre diplomants. Le MOOC « Strategies diagnostiques des cancers » sera dispense a l’automne 2016 sur la plateforme France universite numerique et aura deux niveaux d’apprenants : les etudiants de premier cycle dans le domaine de la sante et de la biologie et le grand public. Il sera egalement integre a des unites d’enseignement pour des etudiants en medecine des universites Paris Diderot et Paris 13. L’objectif pedagogique de ce MOOC est de transmettre a l’ensemble des apprenants une vision globale des etapes diagnostiques du cancer et des differentes specialites medicales impliquees dans ce diagnostic. La deuxieme semaine d’enseignement de ce MOOC, intitulee « le prelevement tumoral, son analyse macroscopique et microscopique », presente la specialite d’anatomie et cytologie pathologiques avec la prise en charge technique des echantillons tissulaires ou cellulaires et les elements basiques du raisonnement anatomopathologique. A l’issue de ce MOOC, il est prevu de realiser une evaluation de l’impact de cette nouvelle modalite d’enseignement sur la perception de l’anatomie et cytologie pathologiques par le grand public.

Resume Objectif Depuis les dernieres recommandations nationales elaborees par l’Institut national du cancer (INCa) et la Societe francaise de senologie et de pathologie mammaire (SFSPM) sur l’ensemble de la prise en charge diagnostique et therapeutique des carcinomes canalaires in situ (CCIS), de nouvelles publications ont fait emerger des interrogations en termes de bonnes pratiques et sur les possibilites de desescalade therapeutique dans la prise en charge des CCIS. L’actualisation de ces recommandations intervient dans un contexte de questionnement sur le surdiagnostic et son corollaire le surtraitement. Elle met a la disposition des professionnels des informations sur les bonnes pratiques correspondant a l’etat le plus recent des connaissances scientifiques et etudie notamment les possibilites de desescalade therapeutique. Methode Le processus d’elaboration est base sur une revue systematique de la litterature et sur le jugement argumente d’experts cliniciens au sein d’un groupe de travail multidisciplinaire. Avant publication, les recommandations sont revues par plus de cent experts cliniciens independants du groupe de travail. Resultats Cet article presente les recommandations nationales relatives a l’indication de l’IRM, la place de la macrobiopsie en cas de microcalcifications et la conduite a tenir en cas de CCIS de bas grade identifie par biopsie, dans le diagnostic des CCIS.

CONTEXT AND AIMS:Breast cancer prognosis and predictive biomarkers development would allow sparing some patients from chemotherapy or identifying patients for whom chemotherapy would be indicated. In this context, in 2009, the French National Cancer Institute, a National Health and Science Agency dedicated to cancer, in collaboration with the French society of senology and breast pathology (SFSPM) published a report on the assessment of the prognostic and the predictive clinical validity of tissular biomarkers, uPA/PAI-1, Oncotype DX™ and MammaPrint(®), in breast cancer management. They concluded that only the uPA/PAI-1 prognosis value reached the highest level of evidence (LOE I according to Hayes 1998 classification). In 2012, it was decided to update this report since new data have emerged and because information disparities among clinicians have been identified. This article aims to present the main conclusions together with the levels of evidence associated with those conclusions.METHODS:The updating process was based on literature published since 2009 appraisal and on multidisciplinary and independent experts' opinion. The levels of evidence (LOE) used are those of the classification defined by Simon in 2009 (updated Hayes 1998 classification): LOE IA and LOE IB: high level of evidence; LOE IIB and LOE IIC: intermediate level of evidence; LOE IIIC and LOE IV-VD: low level of evidence.CONCLUSIONS:Among patients without lymph-node involvement, uPA/PAI-1, invasion process biomarkers, reach the highest level of evidence for 10 years recurrence free survival prognosis (LOE IA according to Simon). The predictive value to anthracyclins chemotherapy remains to be confirmed. Oncotype DX™ and MammaPrint(®) prognosis and predictive value do not reach the LOE I level. This updating' process confirms the 2009 levels of evidence for all the three biomarkers prognosis value. Besides, concerning Oncotype DX™ and MammaPrint(®), new data do not allow to conclude neither to their complementary clinical information to other clinicopathological existing biomarkers nor to a favorable cost-efficiency ratio in therapeutic decision making and this because of the methodological weakness and uncertainty that are identified in the selected studies. Practically, beyond the prognosis and predictive biomarkers validity, the clinical utility of a new biomarker for chemotherapy indication depends on its clinical added information with regard to validated biomarkers (HR, HER2 and Ki67) and to clinicopathological parameters. Since they are the sole validated biomarkers of the invasion process, uPA/PAI-1 could complete clinical information of other clinicopathological factors and consequently could confer an added clinical value. However, data concerning the impact of this information on chemotherapy clinical indication are lacking.Copyright © 2014. Published by Elsevier Masson SAS., IntroductionDans le cancer du sein, le développement des marqueurs biologiques pronostiques ou prédictifs a pour objectif de mieux identifier les patientes pour lesquelles un traitement par chimiothérapie pourrait être évité ou a contrario indiqué. Dans ce contexte, en 2009, l’Institut national du cancer (INCa), agence sanitaire et scientifique de l’État chargée de coordonner les actions de lutte contre le cancer, avait publié en partenariat avec la Société française de sénologie et de pathologie mammaire un rapport sur l’état des connaissances relatives aux biomarqueurs uPA/PAI-1, Oncotype DX™ et MammaPrint® dans la prise en charge du cancer du sein. Ce rapport avait montré que seule la valeur pronostique d’uPA/PAI-1 atteignait le plus haut niveau de preuve (LOE I selon la grille de Hayes 1998). En 2012, devant la parution de nouvelles publications et la divergence des messages diffusés sur les signatures moléculaires, il a été décidé d’actualiser le rapport de 2009. Cet article présente les principales conclusions accompagnées de leurs niveaux de preuve.MéthodeLe processus de mise à jour s’est appuyé sur l’analyse des données publiées depuis la recherche bibliographique de 2009, complétée par l’avis d’un groupe de travail multidisciplinaire indépendant. Les niveaux de preuve employés sont ceux de la classification définie par Simon en 2009 (grille de Hayes 1998 après mise à jour) : LOE IA et LOE IB : niveau de preuve élevé ; LOE IIB and LOE IIC : niveau de preuve intermédiaire ; LOE IIIC and LOE IV-VD : niveau de preuve faible.ConclusionsChez les patientes sans envahissement ganglionnaire (pN0), uPA/PAI-1, marqueurs d’invasion, ont un niveau de preuve élevé (LOE IA selon Simon) pour la valeur pronostique de la survie sans récidive à 10 ans. Il reste à confirmer leur valeur prédictive de réponse aux anthracyclines. Pour Oncotype DX™ et MammaPrint®, les valeurs pronostique et prédictive n’ont pas atteint à ce jour le niveau de preuve LOE I. Ce travail confirme les niveaux de preuve précédemment établis dans le rapport de 2009. Par ailleurs, les données ne permettent pas de conclure à une valeur ajoutée de Oncotype DX™ et MammaPrint® par rapport aux outils existants. Les données médico-économiques ne permettent pas de statuer sur le rapport coût/efficacité des stratégies utilisant ces tests dans la décision thérapeutique compte tenu d’un niveau de qualité insuffisant pour la plupart des études et d’une forte incertitude mise en évidence par les quelques études bien menées. En pratique, au-delà des niveaux de preuve attribuables à la valeur pronostique et prédictive d’un biomarqueur, l’utilité clinique d’un nouveau marqueur dans l’aide à la prescription d’une chimiothérapie repose sur sa valeur ajoutée par rapport aux marqueurs validés (RH, HER2 et les marqueurs de prolifération comme Ki67) et aux critères anatomo-cliniques. Puisqu’ils sont les seuls marqueurs validés à témoigner du processus d’invasion, uPA/PAI-1 peuvent apporter une information complémentaire et donc avoir une valeur ajoutée par rapport aux marqueurs existants. Les données de la littérature manquent pour apprécier le poids de cette valeur ajoutée dans la décision de prescrire ou non une chimiothérapie.

In patients with triple-negative breast cancer (TNBC), pathology complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This prospective study was designed and powered to investigate the ability of interim (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) to predict pathology outcomes to NAC early during treatment.Consecutive TNBC women underwent (18)FDG-PET/CT at baseline and after two courses of NAC. Maximum standardised uptake value (SUV(max)) in the primary tumour and lymph nodes at each examination and the evolution (ΔSUV(max)) between the two scans were measured. NAC was continued irrespective of PET results. Correlations between PET parameters and pathology response, and between PET parameters and event-free survival (EFS), were examined.Fifty patients without distant metastases were enroled. At completion of NAC, surgery showed pCR in 19 patients, while 31 had residual tumour. Mean follow-up was 30.3 months. Thirteen patients, all with residual tumour, experienced relapse. Of all assessed clinical, biological and PET parameters, ΔSUV(max) in the primary tumour was the most predictive of pathology results (p0.0001; Mann-Whitney-U test) and EFS (p=0.02; log rank test). A threshold of 42% decrease in SUV was identified because it offered the best accuracy in predicting EFS. There were 32 metabolic responders (⩾ 42% decrease in SUV(max)) and 18 non-responders. Within responders, the pCR rate was 59% and the 3-year EFS 77.5%. In non-responders, the pCR rate was 0% and the 3-year EFS 47.1%.Interim (18)FDG can early predict the inefficacy of NAC in TNBC patients. It shows promise as a potential contributory biomarker in these patients.

Epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors have limited use as first-line treatment for mutated EGFR metastatic non–small cell lung cancer. The French National Cancer Institute has installed molecular genetics platforms implementing EGFR and KRAS testing. However, there is considerable uncertainty as to which detection methods should be applied for routine diagnosis. This study aimed to compare the EGFR and KRAS genotyping methods developed by the IFCT/ERMETIC2 network platforms in two blind panels: 25 samples of serial dilutions of cell line DNA (20 centers) and 74 FFPE lung tumor samples (10 centers). The best threshold of mutation detection on cell lines was obtained using allele-specific amplification-based technologies. Nonamplifiable tissue samples were significantly less common when using alternative testing versus direct sequencing [15%; 95% confidence interval (CI), 14%–16% versus 40%; 95% CI, 39%–42%; P

The nuclear estrogen receptors (ER) are the major targets for endocrine treatment of hormone-dependent breast cancers. Hormone therapy blocked endogenous estrogen activation of ER, either by competitive inhibition of endogenous estrogens (selective estrogen receptor modulators – SERM or selective estrogen receptor down regulators – SERD) or by inhibition of estrogen synthesis (aromatase inhibitors) from adrenal androgens in post-menopausal women. The efficacy of these treatments has been shown on large series of breast cancer patients. However de novo or acquired resistance to treatment occurs. The better knowledge of the mechanism of action of such treatment may help to better understand them, and also for the determinism of adverse side effects of the different class of molecules.

Background Digestive metastasis of breast cancer are rare but when they do occur the stomach is one of the commoner sites. Aim To describe the clinical, endoscopic, pathological features and treatment. Methods 35 cases of gastric metastasis were identified retrospectively between 1980 and 2008. Results The location of the gastric metastasis was fundus (n = 15, 43%), antrum (n = 15, 43%) or both (n = 5, 14%). The histological subtype of primary breast cancer was invasive lobular carcinoma in 34 patients (97%). Hormonal receptors were positive in 19 out of 24 cases (79%), two out of 22 analysed were HER2 positive (9%). There were 16 (46%) patients with peritoneal carcinosis. The treatment was chemotherapy (n = 13, 37%), hormonotherapy (n = 2, 6%) or both (n = 13, 37%). The 2-year survival rate after gastric metastasis diagnosis was 53% with a median follow up of 31 months [7–84 months]. Conclusion Ninety-seven percent of gastric metastasis from breast cancers are derived from invasive lobular carcinoma. Seventy-nine percent of these are HER+ and comparison with the original histopathological slides of primary breast carcinoma should be performed to differentiate gastric metastasis from primary gastric carcinoma. Peritoneal carcinomatosis accompanied gastric metastasis in almost half the cases in this series and treatment was generally chemotherapy.

Despite an obvious central role of p53 in the hallmarks of cancer, TP53 status is not yet used for the management of breast cancer. Recent findings may lead to reconsider the role of p53 in breast cancer. TP53 mutations are the most frequent genetic alterations in breast cancer, observed in 30% of breast carcinomas. Their distribution is highly linked to molecular tumor subtypes found in 26% of luminal tumors (17% of luminal A, 41% of luminal B), in 50% of HER2 amplified tumors, in 69% of molecular apocrine breast carcinomas and in 88% of basal-like carcinomas. The type of mutation is linked to the tumor subtype with higher frequency of base-pair substitutions in luminal tumors, whereas molecular apocrine and basal-like tumors present much higher frequency of complex mutations (deletions/insertions). The timing of TP53 mutation also depends on the tumor subtype, being the first important event in luminal tumors but occurring after PTEN loss in basal-like tumors. Regarding response to cytotoxic chemotherapy, the situation is far from the p53-dependent apoptosis paradigm with subsequent clinical response. We reported that TP53 mutated non inflammatory locally advanced breast carcinomas had a high rate of complete pathological response to dose-dense doxorubicin-cyclophosphamide chemotherapy, while TP53 wild-type (WT) tumors never achieved complete response. Using human breast cancer xenograft models, we suggested that this could be due to the induction of senescence in TP53 WT tumor cells. A recent work confirmed these findings in MMTV-Wnt1 mammary tumors, showing that growth arrest and senescent phenotype, not apoptosis, were induced in TP53 WT tumors following doxorubicin treatment, while lack of arrest in mutant tumors resulted in aberrant mitoses, cell death and a superior clinical response. Furthermore, in ER positive (ER(+)) breast tumors, it has been recently reported that ER represses the p53-mediated apoptotic response induced by DNA damage. Taken together, these data can help to better understand p53-mediated response to doxorubicin-based chemotherapy in breast cancer: in ER(+) TP53 WT breast cancers, ER-induced inhibition of p53 apoptotic response would lead preferentially to tumor cell senescence and subsequent resistance to treatment. Conversely, in ER negative (ER(-)) TP53 mutated breast cancers, accumulation of genetic abnormalities would lead to mitotic catastrophe and subsequent better response. In view of these recent results, p53 impact in breast cancer should be reconsidered.

Hormone receptor content is the most useful parameter for predicting hormone response therapy in breast cancer. The high frequency of primary and secondary resistance to treatment makes it necessary to find out other parameters in order to improve the prediction of response to treatment. The newly described estrogen receptor beta (ERbeta) is a potential candidate. Using real-time quantitative RT-PCR, we evaluated estrogen receptor alpha (ERalpha), ERbeta, and progesterone receptors (PR) in comparison with ERalpha and PR protein content measured with the enzyme immunoassay (EIA), in a retrospective series of 98 breast tumors. We obtained a highly significant correlation between mRNA and EIA assays for ERalpha and PR (r=0.79 and r=0.71, respectively; P

The recent literature shows that interest in ocular adnexal lymphomas and their biologic and clinical characteristics—along with their possible association with Chlamydia psittaci infection and therapeutic management with rituximab or anti-Chlamydia psittaci antibiotic therapy—is considerable. These new data have modified the previously reported features of this disease and have made an updated review of the literature necessary. The aims of this review are to present the current knowledge on the biology of these lymphomas, their clinical features and prognostic factors, and the panel of all available treatment options.

H466-B and T47-D breast carcinoma cell lines were treated with recombinant gamma interferon (r gamma IFN) to study major histocompatibility complex (MHC) class I and class II antigen responses. Untreated H466-B cells released B2 microglobulin (B2M) into the culture medium and expressed B2M and class I heavy chain on 100% of the cells. The expression of class II antigens (DR) was limited to 8 +/- 4% of the cells. This subpopulation was isolated by cell sorting and labelled with 35S methionine. Protein extracts were immunoprecipitated with anti-DR antibody and subjected to two dimensional non-equilibrium pH gradient electrophoresis (2D-PAGE). A normal pattern of expression of invariant, alpha and beta chains was shown. The MHC antigenic expression of H466-B parental cell line was not modified by interferon treatment. Untreated T47-D cells did not release B2M into the culture medium, expressed B2M and class I heavy chain on 100% of the cells but did not express class II molecules using radio-immunoassay or 2D-PAGE. As early as 24 h after r gamma IFN addition, T47-D cells released B2M into the medium, B2M and class I heavy chain were significantly greater than that of untreated cells, and class II antigenic expression was found, all these in a dose dependent manner. 2D-PAGE analysis of class II antigens revealed the profile of human DR molecules but this expression seemed incomplete since only single alpha and beta spots were detected suggesting a possible defect in the sialilation of DR molecules. These results show a heterogeneity in MHC antigenic responses to r gamma IFN and suggest that synthetized class II molecules may be incompletely processed.