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The study aims to describe the course and management of non-infectious uveitis during pregnancy and postpartum period in European populations.A retrospective observational study in two tertiary centers in France was performed. Pregnant patients during the follow-up of a non-infectious uveitis as well as those with new-onset uveitis were included. The medical records were analyzed with a systematic collection of the characteristics of the uveitis, the treatment and evolution of the uveitis, and the course of the pregnancy including obstetric complications.Seventy-nine pregnancies in 59 women were included: 48 patients (68 pregnancies) were followed for uveitis and 11 had a new-onset uveitis diagnosis. Most patients had idiopathic uveitis (32.2%) or sarcoid uveitis (27.1%). Among the patients followed for uveitis at the time of conception, there were 18 relapses (26.5%) requiring treatment escalation. Relapses occurred mainly in the two first trimester (n = 12) or during the postpartum period (n = 5) and were significantly associated with an active uveitis at the time of conception (OR = 9.2, 95% CI [1.57-48.4], p = 0.01). The characteristics of the new-onset uveitis were similar to those already existing before pregnancy. Obstetric complications occurred in 25 pregnancies (31.6%), mainly gestational hypertension and gestational diabetes.The frequency of non-infectious uveitis relapses decreases as pregnancy progresses, in agreement with data from other non-European studies. However, multidisciplinary monitoring should be advised, especially to uncontrolled patients at the time of conception.

Acute Parvovirus B19 (PVB19) infection is responsible for erythema infectiosum in children and non-specific polyarthralgias in immunocompetent adults associated with skin lesions and rarer manifestations (hepatic, neurological, cardiac or nephrological). In immunocompromised patients, cytopenias are more frequent and in some cases, viremia persists and is responsible for PVB19 chronic infection. PVB19 is responsible for pure red cell aplasia during chronic hemolytic diseases. Acute PVB19 infection is a differential diagnosis of some autoimmune diseases and has been suspected to be a trigger for some autoimmune diseases because of its ability to promote the emergence of autoimmune markers. Mechanisms of molecular mimicry, induction of apoptosis and activation of enzymes have been demonstrated, explaining in part the production of autoantibodies during infection. However, the demonstration of a causal relationship in the triggering of autoimmune disease remains to be done. This review provides a synthesis of the PVB19 infection clinical data in adults with a particular focus on these links with autoimmunity.

Sarcoidosis can develop into a chronic disease in about 30% of cases. When general treatment is indicated, corticosteroids are the first-line treatment. More than one third of patients treated with corticosteroids receive a steroid-sparing agent. Although methotrexate is the most commonly used sparing agent, synthetic antimalarials have been used for more than fifty years on the basis of small, randomised, therapeutic trials. Despite this low level of evidence, chloroquine or more often hydroxychloroquine are used in daily practice, particularly to treat skin, bone and joint sarcoidosis, as well as hypercalcemia and certain types of uveitis. This review summarises the state of knowledge on steroid-sparing therapy in sarcoidosis, particularly in its extra-pulmonary form. These data support the need for good quality therapeutic trials to validate the use of hydroxychloroquine in this specific indication.

Systemic diseases, which are in France mainly monitored in internal medicine, affect multiple organs or tissues. While cutaneous or articular manifestations are the most common, neurological involvement is often associated with severity. Diagnosis of peripheral (e.g, neuropathies) or central (e.g, myelitis) nervous disorders is quite easy through clinical examination and dedicated complementary tests. However, neuropsychological manifestations that affect cognition, including memory, attention, executive functions or reasoning, are difficult to diagnose, sometimes trivialized by practitioners. Their causes are often numerous and interrelated. Nevertheless, these cognitive manifestations are closely related to patients' quality of life, affecting their social life, family dynamics and professional integration but also the treatment adherence. The purpose of this review, focused on the example of systemic lupus erythematosus, is to raise awareness of cognitive dysfunction in systemic diseases including their management from diagnosis to treatments. The final aim is to go further into setting up research groups and care programs for patients with cognitive impairment followed in internal medicine.

Ocular tuberculosis (TB) diagnosisremains difficult and quantiferon (QFT) contribution needs still yet to be specified, despite its generalization in France. The purpose of this observational study is to assess in which ocular inflammation (OI) presentation QFT is prescribed and to evaluate the added value of new QuantiFERON®-TB Gold Plus (QFT-Plus) test for diagnosis ocular TB diagnosis.Monocentric, observational study, carried out in an ophthalmology department over a period of 5 months. Inclusion criteria were defined as an existence of an OI for which a QFT-Plus test was part of the etiological investigations. Of the 316 consecutive files, 72 were excluded (indeterminate test, prescription before anti-TNFα or immunosuppressant initiation, missing data, wrong indication) and 244 were selected and divided into two groups: group one (anterior uveitis/episcleritis, n=129) and group two (intermediate/posterior uveitis/optic neuritis/ocular myositis, n=115). All positive QFT patients underwent an etiological investigation including thoracic imaging.Forty-five patients, aged 52±12 years, had positive QFT (18.5%), including 18 patients for group 1 and 27 for group 2. Living in TB-endemic area, TB exposure and chest imaging abnormalities were identified in 70%, 27% and 22% of cases, respectively. OI was chronic in 36% of cases (group one, 4/18; group two, 12/27). None of the 18 patients, in group 1, received anti-tuberculosis treatment (ATT) or experienced a relapse during one-year follow-up. Four QFT+ patients, from group 2 (15%) had another associated disease explaining their uveitis. Among the 23 other patients without identified etiology, 13 had at least one relevant ophthalmological signs predictive of TB uveitis (posterior synechiae, retinal vasculitis and/or choroidal granuloma) (59%). Eleven patients received a 6-month ATT trial. Radiological abnormalities and granulomas at angiography were significantly more frequent among treated patients (p=0.03 and 0.001, respectively). A full OI recovery was observed for 8 patients (73%), considered ex-post as ocular TB. Nine patients in group 2 received rifampicin/isoniazid dual therapy for 3 months, but no conclusion could be drawn as to the benefit of such prescription on OI. QFT rate comparison, according to CD4 stimulation by ESAT-6/CFP-10 peptides or by CD4/CD8 co-stimulation, was comparable and found only 4 cases of discrepancy (1.6%). None of these 4 cases had ocular TB diagnosis.Positive QFT frequency among patients consulting for posterior OI remains high. In this study, radiological abnormalities and granulomas at angiography seemed to be more closely related to clinician decision for starting ATT trial in QFT+ patients, which was effective in 73% of cases. QFT-Plus does not seem more relevant than QFT-TB in exploring an OI. Prospective studies are necessary to codify QFT management in the etiological assessment of OI and clearly define ATT trial indications as well as their modalities.

Spontaneous adrenal hemorrhages (AH) are a rare condition with no consensus about their management.Patients were identified using the Medicalization of the Information System Program database, imaging software and a call for observations to internists, intensivists and obsetricians working at our institution. Adult patients whose medical records were complete and whose diagnosis was confirmed by medical imaging were included.From 2000 to 2007, 20 patients were identified, including 15 were women. The clinical onset of AH was non-specific. In five cases, AH occurred during pregnancy; four of them were unilateral and right sided. The etiology of the other fifteen (bilateral adrenal hemorrhage in 11) were as follows: antiphospholipid syndrome (n=8), heparin-induced thrombocytopenia (n=4), essential thrombocythemia (n=3), spontaneous AH due to oral anticoagulants (n=1), complication of a surgical act (n=3), and sepsis (n=3). In seven cases, two causes were concomitant. The diagnosis of AH was often confirmed by abdominal CT. An anticoagulant treatment was initiated in 16 cases. Ten of the eleven patients presenting with bilateral adrenal hematomas were treated using a long-term substitute opotherapy. One patient died because of a catastrophic antiphospholipid syndrome.The clinical onset of HS is heterogeneous and non-specific. The confirmatory diagnosis is often based on abdominal CT. The search for an underlying acquired thrombophilia is essential and we found in this study etiological data comparable to the main series in the literature. Adrenal insufficiency is most of the time definitive in cases of bilateral involvement.

International audience; Primary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P

In the past ten years, the better understanding of the pathophysiological mechanisms underlying inflammatory and autoimmune diseases has led to the emergence of many targeted therapies. Among them, the Janus kinase inhibitors are acting upstream in the inflammatory cascade of several key cytokines in disorders such as rheumatoid arthritis, ulcerative colitis or psoriasis. At the moment, these three diseases represent the only indications validated by the FDA and the EMA of the use of JAK inhibitors apart from hematology. Preclinical data and therapeutic trials indicate their efficacy in other autoimmune or inflammatory conditions, such as lupus, dermatomyositis, ankylosing spondylitis, sarcoidosis and giant cell arteritis. This review provides a summary of current use and advancement of knowledge in the use of JAK inhibitors in pathologies faced by internists.

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.

Introduction Parmi les manifestations de la maladie thromboembolique veineuse (MTEV), entite regroupant thrombose veineuse proximale et embolie pulmonaire, on observe une thrombose de la veine cave inferieure (TVCI) dans 4 a 15 % des cas. C’est une localisation peu frequente et il existe a ce jour peu de series publiees sur le sujet. Le but de notre etude concernant la TVCI est de decrire les caracteristiques cliniques des patients, les caracteristiques de la maladie (etiologie, pronostic) et les traitements utilises. Materiels et methodes Nous avons realise une etude observationnelle, retrospective, bicentrique, controlee sur 2 centres hospitalo-universitaires francais entre mars 2010 et novembre 2017. Nous avons recueilli les donnees des patients atteints de TVCI (groupe TVCI issus des deux CHU) et les avons compares avec les donnees des patients atteints de maladie thromboembolique veineuse sans TVCI (groupe controle issu d’un seul CHU). Les donnees ont ete recueillies via le dossier patient informatise. Resultats 165 cas de patients porteurs de TVCI ont ete identifies (âge median 62 ans, 43 % de femmes) pour 727 patients atteints de maladie thromboembolique veineuse hors TVCI (âge median 69 ans, 54 % de femmes). La frequence de TVCI etait de 11 %. Les patients du groupe TVCI presentaient une embolie pulmonaire concomitante dans 35 % des cas. Il existait une pathologie associee a la thrombose chez 139 patients (84 %). Les principales causes de thromboses dans notre cohorte etaient l’existence d’une pathologie abdominale sous-jacente (71 %) et l’existence d’une neoplasie associee (62 %). La neoplasie n’etait presente que chez 140 patients soit 20 % du groupe controle (p Conclusion Cette cohorte de grande taille permet de preciser les determinants de la TVCI dans le spectre de la MTEV. La cause la plus frequente de thrombose de la veine cave inferieure est l’existence d’une neoplasie, principalement abdominale. A contrario, la place pour la recherche de syndrome des anticorps anti-phospholipides ou de thrombophilie acquise est limitee. La mortalite est plus importante en TVCI, probablement du fait de la neoplasie sous-jacente.

Etat de la question Le lupus erythemateux systemique (LES) est une maladie auto-immune rare impactant lourdement la qualite de vie (QdV) des patients. La plupart des etudes longitudinales precedentes portaient sur des questionnaires generiques et ne detaillaient pas l’influence du type de poussee clinique sur l’evolution de la QDV. Notre etude avait pour objectif d’evaluer l’evolution de la qualite de vie specifique dans les 18 mois suivant une poussee clinique, a l’aide d’une approche basee sur la theorie de reponse aux items. Materiel et methodes La cohorte prospective longitudinale francaise EQUAL est constituee de patients atteints de LES suivis pendant deux ans. La QDV specifique selon le LupusQol et le SLEQOL a ete recueillie tous les trois mois. L’activite lupique selon le SELENA-SLEDAI (SFI) et le SELENA-SLEDAI revise (SFI-R) a ete evaluee tous les six mois. La reponse aux items des questionnaires specifiques LupusQoL et SLEQOL par des patients dans les 18 mois (a 6, 12 et 18 mois apres une poussee) suivant une poussee clinique a ete comparee a celle des patients sans poussee grâce a un modele lineaire logistique a hypotheses assouplies pour les dimensions de chaque questionnaire. Resultats Entre decembre 2011 et juillet 2015, 336 patients ont ete inclus (89,9 % de femmes). Les domaines du LupusQol et du SLEQOL concernant la qualite de vie physique (sante physique, fonctionnement physique et douleur) etaient les plus impactes par les poussees osteoarticulaires et cutanees (perte d’independance, ralentissement moteur, difficulte a la marche, impact de la douleur sur les activites, le sommeil, la mobilite, inquietude lie a la douleur articulaire, sentiment de gene pour les autres et de tristesse). Les items impactes par la poussee cutanee concernaient egalement les problematiques d’image de soi. Les poussees neurologiques ou psychiatriques impactaient plus severement la qualite de vie specifique. La qualite de vie des patients est modifiee jusqu’a 18 mois apres une poussee. Conclusion Les resultats d’analyse selon la theorie de reponse aux items permettent de reperer les items qui representent le mieux l’evolution de la qualite de vie des patients. Les items portant sur la sante physique et sur la douleur sont les plus sensibles aux variations de QDV apres une poussee osteoarticulaire ou cutanee, indiquant que cette preoccupation des patients s’ameliore dans les six a 18 mois apres une poussee.

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures).

Inflammatory orbitopathies relate to an inflammatory state originating within the orbit and its adnexes, except the inner ocular globe. Orbital inflammation (OI) may be either localized manifestation of a proven or like autoimmune disease, or local response from immune system against infectious, structural or tumoral antigens. We review the clinical manifestations of OI, which provide helpful clues to the diagnosis and describe the inflammatory, infectious and neoplastic conditions classically associated with OI. Autoimmune diseases are probably the most common causes of OI associated with a bilateral dacryoadenitis (e.g., sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease). We focused on a major part of the IgG4-RD spectrum, the IgG4-related orbital disease which has been recently described and the idiopathic orbital inflammation syndrome that one should consider in patients 40 years of age or older with non specific inflammation OI on biopsy but without underlying local or systemic disease. An algorithm for the diagnostic approach of OI was proposed. If systemic explorations fail to diagnose an underlying disease, histopathologic control is required for distinguishing non-specific OI from other differential diagnosis, especially lymphoma. In the cases of pure myositic locations and posteriorly located tumours where biopsy could damage to the optic nerve, analysis of orbital lesions in T2W IRM sequence may be helpful to distinguish idiopathic OI (IOI) from lymphoma. When the diagnostic work-up fails, a corticosteroid trial could be used, but its beneficial effect has to be cautiously interpretated before definitively diagnosing IOI. Finally, treatments used in main infllammatory orbitopathies were also reviewed.

Scleritis is an inflammatory disease of the sclera; outer tunic of the eye on which the oculomotor muscles are inserted. It can be associated with a systemic disease up to one time out of 3. These associated diseases are mainly rheumatoid arthritis, vasculitis, including granulomatosis with polyangiitis in the first line and spondyloarthropathies. Before mentioning such an etiology, it is necessary to eliminate an infectious cause, mainly herpetic, which is regularly underestimated. The classification of scleritis is clinical. We distinguish between anterior scleritis and posterior scleritis. Anterior scleritis is diffuse or nodular, usually of good prognosis. Anterior necrotizing scleritis with inflammation is often associated with an autoimmune disease, necrotizing scleritis without inflammation usually reflects advanced rheumatoid arthritis. The treatment of these conditions requires close collaboration between internists and ophthalmologists to decide on the use of corticosteroid therapy with or without immunosuppressors or biotherapies.

Sarcoidosis is one of the leading causes of inflammatory eye disease. Any part of the eye and its adnexal tissues can be involved. Uveitis and optic neuropathy are the main manifestations, which the internists face. This review reports the state of knowledge for these two ocular involvements and proposes an assessment-algorithm for sarcoidosis in patients with suspected sarcoid uveitis. Two groups of patients with sarcoid uveitis can be distinguished: one young and multiethnic group in which ophthalmological findings are various and another group of elderly Caucasian women with mostly chronic posterior uveitis. Clinically isolated uveitis revealing sarcoidosis remains a strictly ocular condition in a large majority of cases. Although it could be a serious condition involving functional prognosis, an early recognition in addition to a growing therapeutic arsenal including intravitreal implant seems to have improved visual prognosis of the disease in the last years. Systemic corticosteroids are indicated when uveitis does not respond to topical corticosteroids or when there is bilateral posterior involvement, especially macular edema and occlusive vasculitis. In up to 25% of cases that require an unacceptable dosage of corticosteroids to maintain remission, additional immunosuppression is used, including methotrexate, azathioprine, and mycophenolate mofetil. Regarding systemic sarcoidosis, infliximab and adalimumab have been successfully used for the treatment of refractory or sight-threatening disease. Optic neuropathy often affects women of African and Caribbean origin. Some authors recommend that patients be treated with high-dose corticosteroids and concurrent immunosuppression from the onset for this manifestation, which may be associated with a poorer outcome.

Diagnostic work-up of uveitis involves many uncertainties. Search for an etiology should take into account the epidemiology of uveitis and focus on the most severe diseases or those, which can be treated. This work was undertaken to establish recommendations for the diagnosis work-up of uveitis.Recommendations were developed by a multidisciplinary panel of 15 experts, including internists, ophthalmologists and a rheumatologist and are based on a review of the literature with regard to effectiveness of investigations and the results of the ULISSE study, which is the first prospective study assessing the efficiency of a standardized strategy for the etiological diagnosis of uveitis. Children, immunocompromised patients, severe retinal vasculitis and specific ophthalmological entities are excluded from these recommendations.Investigations should be first guided by the history and physical examination. Serological screening for syphilis is the only test appropriate in all forms of uveitis. If no diagnosis is made after this stage, we propose investigations guided by the anatomic characteristics of uveitis. It includes HLA B27 testing (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin converting enzyme, interferon-gamma release assay and chest CT (chronic uveitis), cerebral MRI and anterior chamber tap with IL10 analysis (intermediate or posterior uveitis in patients over 40 years). Investigations ordered in the absence of orientation are almost always unhelpful.We propose a strategy for the etiologic diagnosis of uveitis. The recommendations should be updated regularly. The efficiency of more invasive investigations has yet to be evaluated.

The French Agency for Health Safety of Products published recommendations of good practices (RGP) for the treatment of venous thromboembolic disease in 2009. Four of these recommendations apply to the initial management of the disease, with the objective of this study is to determine whether the development and diffusion of the four RGP has had an impact on the practice.A retrospective before/after study comparing 132 patients treated in emergency department of the Civil Hospices of Lyon for pulmonary embolism (PE) and/or deep venous thrombosis (DVT) in 2008-2009 ("before") and 153 patients in 2010-2011 ("after").In the "before" period, 70 patients were treated for DVT and 62 patients for PE. In the "after" period, 50 patients were treated for DVT and 103 patients for PE. The compliance rate was not significantly different for the two periods for each RGP except for the indication of low molecular weight Heparin (LMWH) or fondaparinux in the absence of severe renal failure (21% "before" vs. 45% "after"; P=0.02) for patients with PE. Management for the four recommendations was conform for 5.6% of eligible patients in the "before" period and for 3.7% for the "after" period.Our study shows that globally there is no impact of RGP. The reasons appear multiple with first, the mere dissemination and the absence of implementation of these guidelines.

International audience; The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection

Background: Preclinical and retrospective clinical data suggest that ≥3T is a biomarker for poor prognosis and resistance to paclitaxel in breast cancer (BC). Preclinical studies have demonstrated that Ixa has activity in ≥3T over-expressing xenograft models resistant to taxanes and Ixa has shown clinical activity in BC patients with high ≥3T mRNA levels [Horak et al., J Clin Oncol 27:15s, 2009 (suppl; abstr 3587]. Dako and BMS have developed an IHC assay for detection of ≥3T to explore the potential of ≥3T as a biomarker to select BC patients that may benefit from Ixa. A neoadjuvant BC study comparing ixa to weekly paclitaxel employs this assay to assess ≥3T expression levels in patients’ tumor samples. Here we describe the application and initial validation testing of the assay in BC tumor samples. Methods: An IHC assay employing a murine monoclonal anti-≥3T antibody (TUJ1) was developed to assess ≥3T expression in formalin-fixed paraffin-embedded tissue specimens. Banked specimens for initial testing included 233 cases of invasive BC. Results: Patterns of ≥3T staining were typically homogeneous cytoplasmic staining with normal tissue elements such as endothelial cells and nerve cells serving as internal positive controls. Staining intensity was scored as 0, 1+, 2+ or 3+ with 0 being no visible staining and 2+ being equal to that of the internal positive control. Tumors with ≥50% cells staining ≥2+ were defined as positive for ≥3T based on previous published studies. Of the 233 breast tumors, 81 (35%) were positive and 152 (65%) were negative for ≥3T expression. HER2 status was defined for 128 of these specimens, with 37 of them (29%) found to be HER2 positive. Comparison of the samples with defined HER2 status demonstrated similar patterns of ≥3T expression, with 15 (40.5%) of the HER2+ samples being positive for ≥3T and 31 (34.1%) of HER2- specimens expressing elevated levels of ≥3T. In pathologist training exercises the inter-reader and intra-reader agreement of ≥3T scoring exceeded 85%. Antigen stability has been confirmed and other assay validation efforts are ongoing. Conclusions: These findings are consistent with previously reported data on ≥3T expression in breast cancer, and support the use of this ≥3T IHC assay in studies with ixabepilone. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-06.

Resume Introduction Plusieurs auteurs ont evalue la relation entre l’expression de la β-tubuline de classe III et le devenir des patients porteurs d’un cancer du poumon non a petites cellules (CPNPC) traites par des agents antitubulines (AAT). Etat des connaissances Un haut niveau d’expression de β-tubuline de classe III a ete correle avec une moindre reponse ou une survie plus courte chez les patients presentant un CPNPC avance traite par taxanes et vinorelbine. Deux etudes ont montre que les patients traites par paclitaxel dont les tumeurs exprimaient un haut niveau de β-tubuline de classe III avaient une moindre reponse et une survie plus vite, tandis que cette variable n’avait pas de valeur predictive chez les patients ne recevant pas d’AAT. A l’oppose, l’analyse des tumeurs des patients operes porteurs d’un CPNPC de l’essai JBR-10 a montre que la chimiotherapie par cisplatine/vinorelbine semblait neutraliser la valeur pronostique negative de l’expression de β-tubuline de classe III et que le benefice de la chimiotherapie etait plus important pour les patients ayant un haut niveau d’expression. Perspectives Dans le CPNPC avance, un haut niveau d’expression de β-tubuline de classe III pourrait orienter le choix de la chimiotherapie vers un protocole sans taxanes. Les epothilones apparaissent potentiellement interessantes dans ce contexte. Conclusions L’expression de la β-tubuline de classe III emerge comme un marqueur de resistance aux taxanes dans le CPNPC avance, ainsi qu’un marqueur pronostic pour le devenir des patients ayant une maladie localisee.