title: Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the Lung.
abstract: BACKGROUND
  Mucin-rich lung adenocarcinomas (ADCs), namely mucinous and colloid ADCs, are classified as ADC variants according to the World Health Organization 2015 classification. A correlation between morphological patterns and mutational status of these rare entities is not well established.
  
  
  METHODS
  We investigated the mutational profile of mucin-rich lung ADCs in correlation with histopathological and morphological features with the goal of identifying biological tumor characteristics of potential prognostic and therapeutic interest. A series of 54 surgically resected primary mucinous lung ADC samples were retrospectively analyzed for clinicopathological characteristics and by targeted next-generation sequencing.
  
  
  RESULTS
  Fifty cases were invasive mucinous ADCs (32 pure and 18 mixed) and four were colloid-predominant ADCs. Invasive mucinous ADC cases with a pure mucinous pattern were associated with a lower risk of vascular invasion (p = 0.01), absence of signet ring cells (p = 0.03), negative nodal status (p = 0.006), and early clinical stage (p = 0.02). The most prevalent mutations involved the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and tumor protein p53 gene (TP53). Most mutations clustered in the mitogen-activated protein/protein kinase B pathway and in the p53/DNA repair pathway. A few uncommon epidermal growth factor receptor gene (EGFR) mutations were found. A correlation between a higher number of mutations and favorable clinical outcome was seen (p < 0.001).
  
  
  CONCLUSIONS
  Our data showed that mucinous ADCs have peculiar pathological and molecular features that might suggest the need for a differentially tailored therapeutic approach compared with that to conventional lung ADC.
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Luisella
authors.initials: L
authors.lastname: Righi
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Vatrano
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy; Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Di Nicolantonio
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Massa
authors.affiliation: Pathology Unit, University of Modena, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Pathology Unit, Department of Oncology and Advanced Technologies, Azienda Arcispedale S. Maria Nuova/Istituto Di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cavazza
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Votta
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Izzo
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lo Iacono
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ardissone
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy. Electronic address: giorgio.scagliotti@unito.it.
authors.forename: Giorgio Vittorio
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy; Pathology Unit, City of Health and Science, Torino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D011905:Genes, ras; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies
keywords: Lung; Mucinous adenocarcinoma; Mutation; Next-generation sequencing