Isabelle Soubeyran

Obvious peritumoral emboli: an elusive prognostic factor reappraised. Multivariate analysis of 1320 node-negative breast cancers

This study was conducted to determine the prognostic influence of obvious peritumoral vascular emboli as prospectively determined by a simple routine slide examination in patients with operable node-negative breast cancer. Obvious peritumoral emboli (OPE) were defined by the presence of neoplastic emboli within unequivocal vascular lumina (including both lymphatic spaces and blood capillaries) in areas adjacent to but outside the margins of the carcinoma. OPE were assessed routinely on 5 microns thick haematoxylin and eosin-stained sections for each of 1320 primary operable node-negative breast cancers from 1975 to 1992 at our institution. OPE and other prognostic variables (tumour size, SBR grade, oestrogen and progesterone receptor status) were correlated to overall survival (OS) and metastasis-free interval (MFI) by means of univariate and multivariate analysis with a median follow-up of 103 months. OPE were found in 19.5% of tumours. In univariate analysis, OPE were related to tumour size (P = 6.3 x 10(-5)) and histologic grade (P = 4.9 x 10(-7)). Statistically significant correlations were found with OS (P = 4.6 x 10(-5)) and MFI (P = 6.4 x 10(-9)). Furthermore, in multivariate analysis, OPE was an independent prognostic variable, the most predictive factor for MFI (P = 7.7 x 10(-7)) before tumour size and grade, and was second after tumour grade for OS (P = 0.002). This study on a large unicentric series and with a long follow-up confirms the prognostic significance of vascular emboli in patients with operable node-negative breast carcinoma. Importantly, vascular emboli were found to be accurately detectable by a simple routine and non-time-consuming method. Therefore, such obvious vascular emboli should be considered as an important cost-effective, prognostic variable in patients with node-negative breast carcinoma.

Impacts des avis diagnostiques de cancérologie en Aquitaine. Étude quantitative, qualitative et médicoéconomique rétrospective sur une année

AIMSnThe goal of this work was to evaluate the impact of expert pathological second opinion on the diagnosis and management of patients with cancer, in a French region (Aquitaine) and with an economic point of view.nnnMATERIAL AND METHODSnThe study was first quantitative, performed retrospectively on all cases of cancer, voluntary sent for a second opinion to an expert pathologist of two centers. Secondly, we restricted the study to lymphoid, melanocytic and soft tissue tumors sent for second opinion. We considered that the expert review had an important diagnostic impact either when the initial pathologist sent the specimen to identify or classify malignant tumor or hesitated between benign and malignant tumor or had no hypothesis, or if there were discordant diagnoses (malignant/benign) between the two pathologists. We considered that the expert review had a high therapeutic impact if the disagreement between initial and expert diagnoses induced a complete modification in therapy. We evaluated the cost of second opinion for the expert centers and the cost of care management.nnnRESULTSnOver the year 2006, the expert centers received 5077 lesions for consultation: 3769 specimens were sent by a pathologist for a second review, 1324 by pathologists of Aquitania and of these, 751 samples were submitted for lymphoid (55%), soft tissues (30%) or melanocytic tumors (15%). There was an important diagnostic impact for 75% of the samples; the impact of the expert review on patient management was considered high for 46% of specimens and the expert pathological diagnosis modified the clinical prognosis for 40% of the specimens. We estimated that for 53 discordant diagnoses (malignant/benign), second opinion allowed an economy of 500,000 euro.nnnCONCLUSIONnExpert second opinion is very important not only for diagnosis and management for patient with cancer but also for economic reasons.

Complete response to exemestane in a patient with a desmoid tumor

Desmoid tumors are rare mesenchymal neoplasms without metastatic potential. Despite the benign nature of this condition, some patients develop disease progression despite all locoregional options for care. Aggressive forms of desmoid tumors may induce morbidity that can lead to physical impairment and mortality that is occasionally observed as a result of local infiltrative growth and tissue invasion, in particular with abdominal disease. Few therapeutic options are available for patients with recurrent/unresectable desmoid tumors. Several studies have suggested the potential benefit of antiestrogens such as tamoxifen in this setting. Here we report the first description of the efficacy of an aromatase inhibitor in a patient with a desmoid tumor.

La numérisation d’images en anatomie-pathologique : application à l’assurance qualité pour le diagnostic de cancer

Resume Objectifs Tester un systeme de double lecture histologique fonde sur l’image numerique pour le diagnostic de cancer. Materiel et methodes Un systeme de numerisation d’images integre au systeme de gestion informatise du laboratoire permet d’illustrer en temps reel l’aspect histologique pour les cas de cancer diagnostiques dans le laboratoire et traites dans notre Centre. Une double lecture de ces cas a ete realisee par l’examen des images numerisees sur une periode de 30 jours d’activite. Les cas revus ont ete classes en tumeur maligne avec type histologique precise, tumeur maligne sans autre indication (SAI) et diagnostic de malignite douteux sur l’aspect des images numerisees. Resultats Pendant la periode d’etude, 204 cas de cancer ont ete diagnostiques dont 178 ont ete numerises (87%). Parmi les cas numerises, 119 (67%) ont ete classes en tumeur maligne avec type histologique precise, 53 (30%) en tumeur maligne SAI et 6 (3%) en diagnostic de malignite douteux. Ces derniers cas ont ete revus histologiquement et correspondaient bien a une tumeur maligne. Le temps passe a une telle relecture a ete d’environ 2 heures par semaine d’activite. Conclusion Le systeme de numerisation d’images peut participer a l’assurance qualite du diagnostic de cancer en permettant une double lecture rapide et efficace.

Targetable Alterations in Adult Patients With Soft-Tissue Sarcomas: Insights for Personalized Therapy

Importance Patients with advanced soft-tissue sarcomas (STS) have a median overall survival of less than 18 months. Identification of molecular abnormalities for which targeted therapies are available or can be developed is critical for improving patient outcomes. Objective To characterize targetable genomic alterations (GAs) in patients with STS. Design, Setting, and Participants This cross-sectional study of next-generation sequencing results from 584 patients with STS included in the AACR GENIE Database. Main Outcomes and Measures Presence of targetable GAs in STS. Results Of 584 patients included in the analysis, 294 (50.3%) were men and 290 (49.7%) were women, with a median age of 56 years (range, 18-89 years). There were 331 (57%) patients with complex genomics sarcomas, 144 (25%) with translocation-related sarcomas, and 112 (18%) with other sarcomas (inactivating mutation, simple amplicon). A total of 2697 alterations were identified in 451 genes (1154 substitutions, 765 gene amplifications, 364 short indels and splicing variants, 346 gene homozygous deletions, and 68 gene rearrangements) with a median of 4 (1-53) per case. In order of frequency, the 20 genes most often altered were: TP53, MDM2, CDK4, RB1, ATRX, CDKN2A, PTEN, NF1, CDKN2B, KMT2D, GLI1, ATM, TERT, PI3KCA, NOTCH1, MAP2K4, ERBB4, ARID1A, TSC2, and TNFAIP3. At least 1 targetable GA was found in 239 cases (41%) with a statistically significant higher number in other and complex genomics sarcomas than in translocation-related sarcomas (respectively other: n=89, 82%, complex: n = 131, 40%, translocation: n = 19, 13%; &khgr;2 test, Pu2009<u2009.001). Conclusions and Relevance Up to 41% of STS harbored at least 1 clinically relevant GA with potential to influence and personalize therapy. Comprehensive genomic profiling can identify novel treatment paradigms to address the limited options and poor prognoses of patients with STS.

High-depth sequencing of paired primary and metastatic tumours: Implications for personalised medicine

BACKGROUNDnNext-generation sequencing of large panel of genes had been associated with clinical benefit in a significant proportion of patients with advanced cancer. However, the molecular profile of the primary tumour from the initial surgical specimen might significantly differ from the molecular profile in a tumour sample obtained from a biopsy of a metastatic site.nnnPATIENTS AND METHODSnWe compare the genetic profile of primary tumours and paired metastases by using a large panel of cancer genes. Training and validation set including a total of 152 primary and metastatic tumour pairs were sequenced (up to 429 genes) focussing on variants described in the Catalogue of Somatic Mutations in Cancer (COSMIC).nnnRESULTSnTraining and validation set including a total of 152 primary and metastatic tumour pairs were sequenced focussing on variants described in COSMIC. Agreement rate between the couples of primary and metastasis on COSMIC variants was 65% (24/37) and 43% (49/115) in the training and validation cohort, respectively. That rose to 74% (20/27) and 58% (42/73) when focussing on targetable mutations. In five cases, the discordance was related to appearance of secondary resistance mutation, giving a targetable refined agreement rate of 67% (67/100).nnnCONCLUSIONnUp to 40% of paired primary tumour/metastases have discordant molecular profile. Liquid biopsies may overcome, in the near future, the limits of tumour tissue genotyping.

Automate à inclusion rapide : l’expérience bordelaise

Resume Le conditionnement actuel des prelevements tissulaires en pathologie, base sur la fixation formolee et l’inclusion par un automate sous vide, n’est plus adapte aux normes sanitaires, a la necessite de preserver les acides nucleiques et a la reduction des delais de rendu des diagnostics. Nous testons depuis 3 ans une nouvelle methode de conditionnement tissulaire basee sur une fixation alcoolique dans le Molecular Fixative ® (MF) et l’automate Xpress ® a inclusion rapide de Sakura™. En utilisant ce systeme, il est possible de traiter les fragments tissulaires en une a deux heures, a condition d’adapter leur prise en charge macroscopique. Le rendu morphologique varie peu de celui des tissus fixes au formol et se traduit par une retraction cellulaire et tissulaire variable selon le tissu et son epaisseur. Des ajustements protocolaires permettent les analyses immunohistochimiques et FISH de la meme facon qu’avec les fixateurs classiques. Les differentes techniques montrent l’integrite de l’ADN et de l’ARN des tissus fixes dans le MF et conditionnes dans l’Xpress ® .