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1. Histopathological subtyping is a prognostic factor in stage IV lung adenocarcinoma

Author

Claire Tissot, Violaine Yvorel, Vanessa Da Cruz, Fabien Forest, Francois Casteillo, Michel Peoc'h, Pierre Fournel, Antoine Luchez, Olivier Tiffet, Sophie Bayle-Bleuez, Centre d'Études de l'Europe Médiane (CEEM EA 2521), and Institut National des Langues et Civilisations Orientales (Inalco)

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Adenocarcinoma of Lung, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Stage (cooking), Neoplasm Staging, Retrospective Studies, Chemotherapy, Performance status, business.industry, Hazard ratio, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Primary tumor, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, KRAS, business
Abstract

Lung adenocarcinoma is a heterogeneous tumor made of different architectural patterns. These tumors are classified into subtypes according to the predominant pattern in the primary tumor because the predominant pattern is related to overall survival. The prognostic role of these subtypes in stage IV disease is not well known, and most lung adenocarcinomas are diagnosed at the stage of metastatic disease. We aimed to evaluate the prognostic role of histopathological subtypes in lung adenocarcinoma metastases in a retrospective study of 253 patients with clinical, histopathological and molecular data. The presence of the solid subtype was related to overall survival (p = 0.045); the median overall survival was 6.8 months (95 % confidence interval (95 %CI) 4.4-9.1) when present and 11.1 months (95 %CI 8.6-21.3) when absent. Thyroid transcription factor 1 (TTF-1) immunohistochemistry was related to overall survival (p < 0.001); the median overall survival was 11.2 months (95 %CI 8.4-17.7) when positive and 4 months (95 %CI 2.3-5.7) when negative. On multivariate analysis, the presence of the solid subtype (p = 0.0036, hazard ratio (HR) 1.55, 95 %CI 1.03-2.34), TTF-1 positivity (p = 0.044, HR 0.64, 95 %CI 0.42-0.98), age

Published
2020

2. Phenotypic and genetic spectrum of alveolar capillary dysplasia: a retrospective cohort study

Author

Jean-Charles Picaud, Jean-Pierre Masutti, Catherine Vincent-Delorme, Vanessa da Cruz, Jamal Ghoumid, Baptiste Savey, Tiffany Busa, Veronique Atallah, Lelia Dreyfus, Ziad Assaf, Laurélia Jourdan-Voyen, Jean-Baptiste Mouton, Dominique Gaillard, Arnaud Molin, Cédric Baumann, Laetitia Lambert, Sonia Bouquillon, Abraham Mounzer, Frédérique Dijoud, Renaud Touraine, Elise Leroy-Terquem, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de cardiopédiatrie, hôpital Necker-Enfants, 75015 Paris, France, Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Anatomie Pathologie, Centre de Pathologie-Est, Hospices Civils de Lyon, Université de Lyon, Lyon, France, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Saint-Etienne, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Systèmes de Référence Temps Espace (SYRTE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction (RADEME), Hôpital Jeanne de Flandre [Lille]-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Clinique de Génétique médicale Guy Fontaine [CHRU LIlle]-Centre de référence maladies rares Anomalies du développement [CHRU Lille], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and PSL Research University (PSL)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Alveolar capillary dysplasia, Male, Pediatrics, medicine.medical_specialty, newborns, Microarray, [SDV]Life Sciences [q-bio], Autopsy, Persistent Fetal Circulation Syndrome, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, pulmonary hypertension, medicine, Humans, genetics, Lung, alveolar capillary dysplasia, 030304 developmental biology, Retrospective Studies, 0303 health sciences, business.industry, Postmenstrual Age, Infant, Newborn, Obstetrics and Gynecology, Retrospective cohort study, Forkhead Transcription Factors, General Medicine, medicine.disease, Pulmonary hypertension, 3. Good health, Pulmonary Alveoli, Pediatrics, Perinatology and Child Health, Cohort, Mutation, Female, Lung tissue, business
Abstract

ObjectiveAlveolar capillary dysplasia (ACD) is one of the causes of pulmonary hypertension. Its diagnosis is histological but new pathogenetic data have emerged. The aim of this study was to describe a French cohort of patients with ACD to improve the comprehension and the diagnosis of this pathology which is probably underdiagnosed.MethodsA retrospective observational study was conducted in French hospitals. Patients born between 2005 and 2017, whose biological samples were sent to the French genetic reference centres, were included. Clinical, histological and genetic data were retrospectively collected.ResultsWe presented a series of 21 patients. The mean of postmenstrual age at birth was 37.6 weeks. The first symptoms appeared on the median of 2.5 hours. Pulmonary hypertension was diagnosed in 20 patients out of 21. Two cases had prolonged survival (3.3 and 14 months). Histological analysis was done on lung tissue from autopsy (57.1% of cases) or from percutaneous biopsy (28.6%). FOXF1 was found abnormal in 15 patients (71.4%): 8 deletions and 7 point mutations. Two deletions were found by chromosomal microarray.ConclusionThis study is one of the largest clinically described series in literature. It seems crucial to integrate genetics early into diagnostic support. We propose a diagnostic algorithm for helping medical teams to improve diagnosis of this pathology.

Published
2019

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