LKB1/STK11 Expression in Lung Adenocarcinoma and Associations With Patterns of Recurrence.
AMP-Activated Protein Kinase Kinases
Adenocarcinoma of Lung
/ diagnosis
Aged
Biomarkers, Tumor
/ metabolism
Disease-Free Survival
Female
Humans
Lung Neoplasms
/ diagnosis
Male
Middle Aged
Neoplasm Recurrence, Local
/ diagnosis
Neoplasm Staging
Prognosis
Protein Serine-Threonine Kinases
/ biosynthesis
Retrospective Studies
Journal
The Annals of thoracic surgery
ISSN: 1552-6259
Titre abrégé: Ann Thorac Surg
Pays: Netherlands
ID NLM: 15030100R
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
24
01
2019
revised:
04
02
2020
accepted:
09
03
2020
pubmed:
23
5
2020
medline:
11
11
2020
entrez:
23
5
2020
Statut:
ppublish
Résumé
Mutations in the serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) have been implicated in mediating resistance to checkpoint blockade among patients with advanced lung adenocarcinoma. We sought to examine the associations between clinicopathologic characteristics, tumor LKB1 expression, features of the immune microenvironment, and postoperative prognosis among patients with early stage lung adenocarcinoma undergoing surgical therapy. Formalin-fixed, paraffin-embedded specimens of patients undergoing resection of stage I to III, chemotherapy-naïve adenocarcinomas (1997 to 2008) were analyzed using tissue microarray sectioning. Sublobar resections were excluded. Intratumoral LKB1/STK11 expression was quantified as H-score. In a subset, tumor-associated immune cell populations were quantified using whole tumor sections in peritumoral and intratumoral compartments. In all, 104 patients met inclusion criteria. Expression of LKB1/STK11 (median H-score 102.9) was higher in women (median 123.3) than in men (100, P = .004) and in never-smokers (median 145) than in former/current smokers (100, P = .002). Expression of LKB1/STK11 was positively correlated with intratumoral infiltration of cluster of differentiation (CD) 3 Low LKB1/STK11 expression is associated with specific patient characteristics and poor postoperative prognosis in chemotherapy-naïve lung adenocarcinoma. Further investigation is warranted to delineate its clinical significance in the context of evaluating novel therapeutic agents in patients with resectable disease.
Sections du résumé
BACKGROUND
Mutations in the serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) have been implicated in mediating resistance to checkpoint blockade among patients with advanced lung adenocarcinoma. We sought to examine the associations between clinicopathologic characteristics, tumor LKB1 expression, features of the immune microenvironment, and postoperative prognosis among patients with early stage lung adenocarcinoma undergoing surgical therapy.
METHODS
Formalin-fixed, paraffin-embedded specimens of patients undergoing resection of stage I to III, chemotherapy-naïve adenocarcinomas (1997 to 2008) were analyzed using tissue microarray sectioning. Sublobar resections were excluded. Intratumoral LKB1/STK11 expression was quantified as H-score. In a subset, tumor-associated immune cell populations were quantified using whole tumor sections in peritumoral and intratumoral compartments.
RESULTS
In all, 104 patients met inclusion criteria. Expression of LKB1/STK11 (median H-score 102.9) was higher in women (median 123.3) than in men (100, P = .004) and in never-smokers (median 145) than in former/current smokers (100, P = .002). Expression of LKB1/STK11 was positively correlated with intratumoral infiltration of cluster of differentiation (CD) 3
CONCLUSIONS
Low LKB1/STK11 expression is associated with specific patient characteristics and poor postoperative prognosis in chemotherapy-naïve lung adenocarcinoma. Further investigation is warranted to delineate its clinical significance in the context of evaluating novel therapeutic agents in patients with resectable disease.
Identifiants
pubmed: 32442617
pii: S0003-4975(20)30724-4
doi: 10.1016/j.athoracsur.2020.03.114
pmc: PMC8215648
mid: NIHMS1712071
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
STK11 protein, human
EC 2.7.11.1
AMP-Activated Protein Kinase Kinases
EC 2.7.11.3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1131-1138Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA070907
Pays : United States
Investigateurs
J Jack Lee
(JJ)
Ara A Vaporciyan
(AA)
Wayne L Hofstetter
(WL)
Reza J Mehran
(RJ)
Stephen G Swisher
(SG)
David C Rice
(DC)
Boris Sepesi
(B)
Garrett L Walsh
(GL)
Carmen Behrens
(C)
Neda Kalhor
(N)
Annikka Weissferdt
(A)
John V Heymach
(JV)
John V Heymach
(JV)
None AstraZeneca
None Bayer
None GlaxoSmithKline
Informations de copyright
Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
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