Luisella Righi1, Simona Vatrano1, Federica Di Nicolantonio2, Federica Massa1, Giulio Rossi3, Alberto Cavazza4, Marco Volante1, Arianna Votta1, Stefania Izzo1, Marco Lo Iacono1, Francesco Ardissone1, Massimo Di Maio1, Silvia Novello1, Giorgio Vittorio Scagliotti5, Mauro Papotti6. 1. Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy. 2. 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. 3. Pathology Unit, University of Modena, Modena, Italy. 4. Pathology Unit, Department of Oncology and Advanced Technologies, Azienda Arcispedale S. Maria Nuova/Istituto Di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy. 5. Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy. Electronic address: giorgio.scagliotti@unito.it. 6. Department of Oncology, University of Torino at San Luigi Hospital, Orbassano, Torino, Italy; Pathology Unit, City of Health and Science, Torino, Italy.
Abstract
INTRODUCTION: 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.
INTRODUCTION: 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 ratsarcoma 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: Alison K Bauer; Misha Umer; Vanessa L Richardson; Amber M Cumpian; Anna Q Harder; Nasim Khosravi; Zoulikha Azzegagh; Naoko M Hara; Camille Ehre; Maedeh Mohebnasab; Mauricio S Caetano; Daniel T Merrick; Adrie van Bokhoven; Ignacio I Wistuba; Humam Kadara; Burton F Dickey; Kalpana Velmurugan; Patrick R Mann; Xian Lu; Anna E Barón; Christopher M Evans; Seyed Javad Moghaddam Journal: JCI Insight Date: 2018-08-09