Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome.
BACKGROUND
Lung adenocarcinoma is histologically heterogeneous and has 5 distinct histologic growth patterns: lepidic, acinar, papillary, micropapillary, and solid. To date, there is no consensus regarding the clinical utility of these patterns.


METHODS
The authors performed a detailed semiquantitative assessment of histologic patterns of 240 lung adenocarcinomas and determined the association with patients' clinicopathologic features, including recurrence-free survival (RFS) and overall survival (OS) rates. In a subset of tumors, expression levels of 2 prognostic molecular markers were evaluated: thyroid transcription factor-1 (TTF-1) (n = 218) and a panel of 5 proteins (referred as the FILM signature index) (n = 185).


RESULTS
Four mutually exclusive tumor histology pattern groups were identified: 1) any solid (38%), 2) any papillary but no solid (14%), 3) lepidic and acinar but no solid or papillary (30%), and 4) acinar only (18%). Patients in group 3 had a higher RFS rate than patients in group 1 (hazard ratio [HR], 0.4510; P = .0165) and group 2 (HR, 0.4253; P = .0425). Solid pattern tumors (group 1) were associated with a lower OS rate than nonsolid pattern tumors (all stages: HR; 1.665; P = .0144; stages I and II: HR, 2.157; P = .008). In the patients who had tumors with a nonsolid pattern, high TTF-1 expression was associated significantly with higher RFS (HR, 0.994; P = .0017) and OS (HR, 0.996; P = .0276) rates in all stages, and a high FILM signature index score was associated with lower RFS and OS rates in all stages (RFS: HR, 1.343; P = .0192; OS: HR, 1.371; P = .0156) and in stages I and II (RFS: HR, 1.419; P = .0095; OS: HR, 1.315; P = .0422).


CONCLUSIONS
The presence of a solid histologic pattern was identified as a marker of unfavorable prognosis in patients with primary lung adenocarcinoma. High TTF-1 expression and low FILM signature index scores were associated with a better prognosis for patients who had tumors with a nonsolid pattern.
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Luisa M
LM
Solis
Carmen
C
Behrens
M Gabriela
MG
Raso
Heather Y
HY
Lin
Humam
H
Kadara
Ping
P
Yuan
Hector
H
Galindo
Ximing
X
Tang
J Jack
JJ
Lee
Neda
N
Kalhor
Ignacio I
II
Wistuba
Cesar A
CA
Moran
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000367:Age Factors; D000368:Aged; D004268:DNA-Binding Proteins / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012737:Sex Factors; D015996:Survival Rate; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C504003:TTF1 protein, human; D014157:Transcription Factors