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

L. Righi, Simona Vatrano, Federica Di Nicolantonio, Federica Massa, Giulio Rossi, Alberto Cavazza, Marco Volante, Arianna Votta, Stefania Izzo, M. Lo Iacono, Francesco Ardissone, Massimo Di Maio, Silvia Novello, Giorgio Vittorio Scagliotti, M. Papotti

Research output: Contribution to journalArticle

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 mucinrich 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 nextgeneration 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). Themost 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.

Original languageEnglish
Pages (from-to)504-515
Number of pages12
JournalJournal of Thoracic Oncology
Volume11
Issue number4
DOIs
Publication statusPublished - 2016

Fingerprint

Mucinous Adenocarcinoma
Neoplasm Genes
Multicenter Studies
Retrospective Studies
Mutation
Colloids
Adenocarcinoma
erbB-1 Genes
Proto-Oncogene Proteins c-akt
p53 Genes
Mucins
Mitogens
Oncogenes
DNA Repair
Sarcoma
Blood Vessels
Neoplasms
Proteins
Adenocarcinoma of lung
Therapeutics

Keywords

  • Lung
  • Mucinous adenocarcinoma
  • Mutation
  • Next-generation sequencing

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung. / Righi, L.; Vatrano, Simona; Di Nicolantonio, Federica; Massa, Federica; Rossi, Giulio; Cavazza, Alberto; Volante, Marco; Votta, Arianna; Izzo, Stefania; Iacono, M. Lo; Ardissone, Francesco; Di Maio, Massimo; Novello, Silvia; Scagliotti, Giorgio Vittorio; Papotti, M.

In: Journal of Thoracic Oncology, Vol. 11, No. 4, 2016, p. 504-515.

Research output: Contribution to journalArticle

Righi, L, Vatrano, S, Di Nicolantonio, F, Massa, F, Rossi, G, Cavazza, A, Volante, M, Votta, A, Izzo, S, Iacono, ML, Ardissone, F, Di Maio, M, Novello, S, Scagliotti, GV & Papotti, M 2016, 'Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung', Journal of Thoracic Oncology, vol. 11, no. 4, pp. 504-515. https://doi.org/10.1016/j.jtho.2016.01.004
Righi, L. ; Vatrano, Simona ; Di Nicolantonio, Federica ; Massa, Federica ; Rossi, Giulio ; Cavazza, Alberto ; Volante, Marco ; Votta, Arianna ; Izzo, Stefania ; Iacono, M. Lo ; Ardissone, Francesco ; Di Maio, Massimo ; Novello, Silvia ; Scagliotti, Giorgio Vittorio ; Papotti, M. / Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung. In: Journal of Thoracic Oncology. 2016 ; Vol. 11, No. 4. pp. 504-515.
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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 mucinrich 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 nextgeneration 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). Themost 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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AU - Righi, L.

AU - Vatrano, Simona

AU - Di Nicolantonio, Federica

AU - Massa, Federica

AU - Rossi, Giulio

AU - Cavazza, Alberto

AU - Volante, Marco

AU - Votta, Arianna

AU - Izzo, Stefania

AU - Iacono, M. Lo

AU - Ardissone, Francesco

AU - Di Maio, Massimo

AU - Novello, Silvia

AU - Scagliotti, Giorgio Vittorio

AU - Papotti, M.

PY - 2016

Y1 - 2016

N2 - 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 mucinrich 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 nextgeneration 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). Themost 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.

AB - 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 mucinrich 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 nextgeneration 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). Themost 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.

KW - Lung

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KW - Mutation

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