Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/43896
Title: In situ growth in early lung adenocarcinoma may represent precursor growth or invasive clone outgrowth – a clinically relevant distinction
Authors: Moore, D
Sereno, M
Das, M
Baena Acevedo, JD
Sinnadurai, S
Smith, C
McSweeney, A
Su, X
Officer, L
Jones, C
Dudek, K
Guttery, D
Taniere, P
Spriggs, R
Le Quesne, J
First Published: 1-Apr-2019
Publisher: Springer Nature for United States and Canadian Academy of Pathology (USCAP)
Citation: Modern Pathology, 2019
Abstract: The switch from in situ to invasive tumor growth represents a crucial stage in the evolution of lung adenocarcinoma. However, the biological understanding of this shift is limited, and ‘Noguchi Type C’ tumors, being early lung adenocarcinomas with mixed in situ and invasive growth, represent those that are highly valuable in advancing our understanding of this process. All Noguchi Type C adenocarcinomas (n = 110) from the LATTICE-A cohort were reviewed and two patterns of in situ tumor growth were identified: those deemed likely to represent a true shift from precursor in situ to invasive disease (‘Noguchi C1’) and those in which the lepidic component appeared to represent outgrowth of the invasive tumor along existing airspaces (‘Noguchi C2’). Overall Ki67 fraction was greater in C2 tumors and only C1 tumors showed significant increasing Ki67 from in situ to invasive disease. P53 positivity was acquired from in situ to invasive disease in C1 tumors but both components were positive in C2 tumors. Likewise, vimentin expression was increased from in situ to invasive tumor in C1 tumors only. Targeted next generation sequencing of 18 C1 tumors identified four mutations private to the invasive regions, including two in TP53, while 6 C2 tumors showed no private mutations. In the full LATTICe-A cohort, Ki67 fraction classified as either less than or greater than 10% within the in situ component of lung adenocarcinoma was identified as a strong predictor of patient outcome. This supports the proposition that tumors of all stages that have ‘high grade’ in situ components represent those with aggressive lepidic growth of the invasive clone. Overall these data support that the combined growth of Noguchi C tumors can represent two differing biological states and that ‘Noguchi C1’ tumors represent the genuine biological shift from in situ to invasive disease.
DOI Link: 10.1038/s41379-019-0257-1
ISSN: 0893-3952
Links: https://www.nature.com/articles/s41379-019-0257-1
http://hdl.handle.net/2381/43896
Embargo on file until: 1-Oct-2019
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2019, Springer Nature for United States and Canadian Academy of Pathology (USCAP). Deposited with reference to the publisher’s open access archiving policy. (http://www.rioxx.net/licenses/all-rights-reserved)
Description: The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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