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 language | English |
|---|---|
| Pages (from-to) | 504-515 |
| Number of pages | 12 |
| Journal | Journal of Thoracic Oncology |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2016 |
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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 journal › Article
}
TY - JOUR
T1 - Retrospective multicenter study investigating the role of targeted next-generation sequencing of selected cancer genes in mucinous adenocarcinoma of the lung
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
KW - Mucinous adenocarcinoma
KW - Mutation
KW - Next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=84962878145&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962878145&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2016.01.004
DO - 10.1016/j.jtho.2016.01.004
M3 - Article
VL - 11
SP - 504
EP - 515
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 4
ER -