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.

Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung

RIGHI, Luisella
First
;
VATRANO, SIMONA;DI NICOLANTONIO, Federica;VOLANTE, Marco;Lo Iacono, M;ARDISSONE, Francesco;DI MAIO, Massimo;NOVELLO, Silvia;SCAGLIOTTI, Giorgio Vittorio
;
PAPOTTI, Mauro Giulio
Last
2016-01-01

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.
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http://dx.doi.org/10.1016/j.jtho.2016.01.004
Lung; Mucinous adenocarcinoma; Mutation; Next-generation sequencing; Oncology; Pulmonary and Respiratory Medicine
Righi, L; Vatrano, S; Di Nicolantonio, F; Massa, F; Rossi, G; Cavazza, A; Volante, M; Votta, A; Izzo, S; Lo Iacono, M; Ardissone, F; Di Maio, M; Novello, S; Scagliotti, Gv; Papotti, M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1595494
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