Clinicopathological and Molecular Study of Peritoneal Carcinomatosis Associated with Non-Small Cell Lung Carcinoma
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Clinicopathological and Molecular Study of Peritoneal Carcinomatosis Associated with Non-Small Cell Lung Carcinoma Hussein Nassereddine 1,2 & Aurélie Sannier 1,3 & Solenn Brosseau 3,4 & Jean-Michel Rodier 5 & Antoine Khalil 3,6 & Simon Msika 3,7 & Claire Danel 1,3 & Anne Couvelard 1,3 & Nathalie Théou-Anton 8 & Aurélie Cazes 1,3 Received: 13 June 2019 / Accepted: 6 August 2019 # Arányi Lajos Foundation 2019
Abstract To retrospectively characterize the molecular features of Non-Small Cell Lung Carcinomas (NSCLC) with peritoneal carcinomatosis (PC), clinicopathological data of 12 patients diagnosed with NSCLC and PC between 2007 and 2016 were collected. Immunohistochemistry and Next Generation Sequencing (NGS) were performed on cases with available material. PC was the initial presentation of NSCLC in 17% of the cases. Overall, patients with PC displayed a poor median survival of 12 weeks. Histology was adenocarcinoma in 11 cases. 37.5% of cases showed PD-L1 immunostaining positivity (50% cut-off). ALK and ROS1 immunostainings were negative. Using NGS, we identified 17 molecular alterations in 9 genes (TP53, KRAS, STK11, BRAF, EGFR, DDR2, ERBB4, SMAD4, CTNNB1) in 88.9% of adenocarcinomas. To the best of our knowledge, 5 of these variants are not referenced in the literature. In conclusion, PC might be the initial presentation of NSCLC. Molecular profiling of our cases did not find any effective targetable alteration, except from high PD-L1 expression. Keywords Peritoneal carcinomatosis . Non-small cell lung carcinoma . NSCLC . Massively-parallel sequencing . Molecular pathology
Introduction Lung cancer is currently the most common cause of cancer death worldwide [1]. Peritoneal carcinomatosis (PC) is considered a rare clinical event in patients with stage IV lung cancer, with a reported incidence of 1.2% to 16% mainly in autopsy studies [2, 3]. It appears to be highly associated with malignant pleural extension [3]. The diagnosis of PC is
generally made by the use of imaging techniques and/or the presence of malignant cells in the ascitic fluid [4]. As the outcome of lung cancer patients after diagnosis of PC is very poor, identification of potential therapeutic targets is a key concern. There are limited data on genomic profiles of peritoneal carcinomatosis associated with non small cell lung carcinoma (PC-NSCLC). Some authors reported EGFR and KRAS mutations, ALK rearrangements and rarely MET
Hussein Nassereddine and Aurélie Sannier contributed equally to this work. * Hussein Nassereddine [email protected] 1
Assistance Publique – Hôpitaux de Paris, département de pathologie, Hôpital Bichat-Claude Bernard, Paris, France
2
Department of pathology, AP-HP, Bichat- Hospital, 46 rue Henri Huchard 75877, 18 Paris Cedex, France
3
Université de Paris, Paris, France
4
APHP, service d’Oncologie Thoracique, Hôpital Bichat-Claude Bernard, Paris, France
5
APHP, service d’Oncologie, Hôpital Bichat-Claude Bernard, Paris, France
6
APHP, service de Radiologie, Hôpital Bichat-Claude
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