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Histologic patterns and molecular characteristics of lung adenocarcinoma associated with clinical outcome
Author(s) -
Solis Luisa M.,
Behrens Carmen,
Raso M. Gabriela,
Lin Heather Y.,
Kadara Humam,
Yuan Ping,
Galindo Hector,
Tang Ximing,
Lee J. Jack,
Kalhor Neda,
Wistuba Ignacio I.,
Moran Cesar A.
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26584
Subject(s) - medicine , adenocarcinoma , hazard ratio , immunohistochemistry , lung , histology , pathology , thyroid , survival rate , gastroenterology , cancer , confidence interval
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. Cancer 2011;. © 2011 American Cancer Society .