Wegener Granulomatosis Revealed by Pleural Effusion

Pulmonary signs are common in Wegener's granulomatosis (WG). However, an initial presentation including pleural effusion has not been described. We describe a case of WG in which pleural effusion was the first clinical manifestation. A 45-year-old man with dorsal pain presented with pleural thickening and effusion, and a visible nodule on a thoracic scan. A dense chronic inflammatory infiltrate was obtained by pleural biopsy and an open lung biopsy revealed necrotizing granulomatous vasculitis. Serologies were positive for antineutrophil cytoplasmic antibodies and antiproteinase 3 antibodies. A diagnosis of WG was conducted and the patient was started on cyclophosphamide and methylprednisolone as an initial treatment, with a favorable evolution. Although pleural effusion is rarely described in WG, this pathology must be considered in the presence of this clinical manifestation

Routine molecular profiling of cancer: results of a one-year nationwide program of the French Cooperative Thoracic Intergroup (IFCT) for advanced non-small cell lung cancer (NSCLC) patients.

International audienceBackground: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. Methods This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. Findings 18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18–98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7–16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8–25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7–38·2] for presence of a genetic alteration vs 33% [29·5–35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0–18·8] vs 9% [6·7–11·9]; p<0·0001). Presence of a genetic alteration was also associated with improved first-line progression-free survival (10·0 months [95% CI 9·2–10·7] vs 7·1 months [6·1–7·9]; p<0·0001) and overall survival (16·5 months [15·0–18·3] vs 11·8 months [10·1–13·5]; p<0·0001) compared with absence of a genetic alteration. Interpretation Routine nationwide molecular profiling of patients with advanced NSCLC is feasible. The frequency of genetic alterations, acceptable turnaround times in obtaining analysis results, and the clinical advantage provided by detection of a genetic alteration suggest that this policy provides a clinical benefit

Bases moléculaires de la progression tumorale dans les lésions prénéoplasiques bronchiques: Approches in situ

In order to identify in preneoplastic bronchial lesions molecular abnormalities characteristic of irrevesibility and tumoral progression, which could serve as markers for surveillance and chemoprevention of high risk patients, we have demonstrated the predictive value of cumulative molecular abnormalities in bronchial carcinogenesis. We have shown a competition between SEMA3F, lost early in carcinogensis and which gene is a candidate suppressor gene with possible proapoptotic properties, and VEGF, implicated in tumoral progression and migration, on their common recetors neuropilines 1 and 2. Furthermore, telomerase, an enzyme which maintains telomere lenght and thus enables immortality, is expressed with the highest levels in basaloid and small cell lung carcinoma. Its nuclear accumulation in non small cell lung carcinoma appears to be correlated with a worse prognosis, protecting tumor cells from an increased genetic instability. In bronchial carcinogenesis, telomerase is re activated early, preceded by telomere shortening which occurs in squamous metaplasia, and is increasingly expressed in dysplasia, along with Rb/p16 and p53 inactivation.Afin de mettre en évidence des signes génétiques et moléculaires d'irréversibilité de lésions prénéoplasiques bronchiques, pouvant améliorer le dépistage, la surveillance et la chimioprévention de patients fumeurs à risque, nous avons démontré la valeur prédictive de l'accumulation d'anomalies moléculaires dans les lésions prénéoplasiques et observé dans ces lésions une compétition sur leurs récepteurs communs les neuropilines 1 et 2 entre la Sémaphorine 3F, perdue précocement et dont le gène est un candidat suppresseur de tumeur proapoptotique, et VEGF, impliqué dans la progression et la migration tumorale, exprimé de façon croissante dans les lésions dysplasiques. Par ailleurs, la télomèrase, enzyme permettant le maintien de la taille des télomères et donc l'acquisition de l'immortalité, est ré exprimée précocement en réponse au raccourcissement télomérique et de façon croissante dans les dysplasies, parallèlement à l'inactivation des verrous du cycle cellulaire p16/Rb et p53

Étude du profil mutationnel K-RAS, EGFR, LKB1 et de la transition épithélio-mésenchymateuse dans une série de 22 carcinomes sarcomatoïdes pulmonaires

Les carcinomes sarcomatoïdes primitifs pulmonaires sont des tumeurs rares, représentant 0,3 à 3% des cancers primitifs pulmonaires. En 2004, l OMS définit dans sa classification le carcinome sarcomatoïde, nouvelle entité, comme toute prolifération capable d offrir de façon permanente des aspects morphologiques de transition épithélio-mésenchymateuse .Les mécanismes de carcinogénèse ont été longtemps débattus. La thèse actuelle propose que les carcinomes sarcomatoïdes dérivent de cellules souches pluri-potentes, capables d une différenciation carcinomateuse et sarcomateuse. Comme pour les carcinomes bronchiques non à petites cellules (CBNPC), on observe la présence de mutations des oncogènes K-RAS et EGFR, en fonction des ethnies et de l exposition tabagique. Les mutations de l EGFR et de K-RAS sont retrouvées dans les carcinomes pléomorphes avec contingent adénocarcinomateux ou à grandes cellules, rarement dans les carcinomes à cellules géantes. Des cas de réponse après chimiothérapie par inhibiteurs de tyrosine kinase chez des patients mutés pour l EGFR invitent à préciser par immuno-histochimie et/ou biologie moléculaire, le phénotype des carcinomes sarcomatoïdes pour aiguiller les analyses moléculaires. Des études supplémentaires du profil mutationnel vis-à-vis de BRAF, des PI3K ou de HER2, récemment décrites dans le CBNPC seraient souhaitables. Si le profil mutationnel ne permet par de différencier les carcinomes sarcomatoïdes des CBNPC, c est la présence d une activation du processus de transition épithélio-mésenchymateuse qui caractérise ces tumeurs. L étude immuno-histochimique confirme l activation du processus de transition épithélio-mésenchymateuse dans les cellules sarcomatoïdes sous forme de perte de la E-cadhérine et acquisition de la vimentine. La répression de l E-cahérine ne semble pas être le seul fait de l action de Snail, ce dernier n étant pas exprimé dans tous les carcinomes sarcomatoïdes de notre série.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Bases moléculaires de la progression tumorale dans les lésions prénéoplasiques bronchiques (approchres in situ)

Afin de mettre en évidence des signes génétiques et moléculaires d irréversibilité de lésions prénéoplasiques bronchiques, pouvant améliorer le dépistage, la surveillance et la chimioprévention de patients fumeurs à risque, nous avons démontré la valeur prédictive de l'accumulation d'anomalies moléculaires dans les lésions prénéoplasiques et observé dans ces lésions une compétition sur leurs récepteurs communs les neuropilines 1 et 2 entre la Sémaphorine 3F, perdue précocement et dont le gène est un candidat suppresseur de tumeur proapoptotique, et VEGF, impliqué dans la progression et la migration tumorale, exprimé de façon croissante dans les lésions dysplasiques. Par ailleurs, la télomèrase, enzyme permettant le maintien de la taille des télomères et donc l acquisition de l immortalité, est ré exprimée précocement en réponse au raccourcissement télomérique et de façon croissante dans les dysplasies, parallèlement à l inactivation des verrous du cycle cellulaire p16/Rb et p53In order to identify in preneoplastic bronchial lesions molecular abnormalities characteristic of irrevesibility and tumoral progression, which could serve as markers for surveillance and chemoprevention of high risk patients, we have demonstrated the predictive value of cumulative molecular abnormalities in bronchial carcinogenesis. We have shown a competition between SEMA3F, lost early in carcinogensis and which gene is a candidate suppressor gene with possible proapoptotic properties, and VEGF, implicated in tumoral progression and migration, on their common recetors neuropilines 1 and 2. Furthermore, telomerase, an enzyme which maintains telomere lenght and thus enables immortality, is expressed with the highest levels in basaloid and small cell lung carcinoma. Its nuclear accumulation in non small cell lung carcinoma appears to be correlated with a worse prognosis, protecting tumor cells from an increased genetic instability. In bronchial carcinogenesis, telomerase is re activated early, preceded by telomere shortening which occurs in squamous metaplasia, and is increasingly expressed in dysplasia, along with Rb/p16 and p53 inactivationGRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Telomerase activation in adenocarcinoma-bronchioloalveolar carcinoma.

International audienc

[Diagnosis of lung cancer. DNA microarrays in thoracic oncology]

National audienceDNA microarrays allow simultaneous measurement of the expression of several thousand genes in a biological specimen. This technique represents a major advance in the analysis of tumour biopsies. It may be used to refine the anatomical- pathological diagnosis at a molecular level and thus lead to better diagnostic and prognostic classification and improved therapeutic decisions