Nonpredominant lepidic pattern correlates with better outcome in invasive lung adenocarcinoma.
OBJECTIVE
Histologic heterogeneity is a typical feature of pulmonary adenocarcinoma. This study aimed to deconstruct the intratumoral growth pattern composition and to examine the prognostic relevance of the current lung adenocarcinoma classification in a series of Finnish lung cancer patients.


METHODS
A cohort of 112 patients with surgically operated stage I-IV lung adenocarcinoma was retrospectively reviewed. Histologic subtyping was performed according to the classification system established by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS). Systematically collected clinical information including survival data was correlated with the subtype status. In addition, emphasis was placed on the nonpredominant histologic patterns, gender and smoking history.


RESULTS
The most common subtype was acinar predominant adenocarcinoma with 56 cases (50%). Most tumors were composed of a mixture of two or more growth patterns, and single pattern tumors were rare (9.8%). Micropapillary predominant adenocarcinoma and solid predominant adenocarcinoma were the subtypes with the lowest disease-specific survival rates (5-year DSS 21.4% and 30.4%; shared mean DSS 46.3 months, p=0.040). A nonpredominant lepidic component was observed in 24 (21.4%) tumors, and its presence predicted a better outcome (mean DSS 127.4 months vs. 55.7 months, p=0.001). This association was confirmed by multivariate analysis (p=0.004). Solid pattern and solid, papillary, micropapillary and cribriform predominant histology associated with smoking (p<0.001), while mucinous pattern was more common in nonsmokers (p<0.001) and in women (p=0.050).


CONCLUSIONS
Micropapillary and solid predominant adenocarcinomas showed significantly lower survival rate than other major subtypes, yet the prognostic value of the current lung adenocarcinoma classification is not limited only to the predominant growth patterns. The more favorable outcome associated with the nonpredominant lepidic pattern further emphasizes the importance of histologic subtyping and assessment of tumor heterogeneity in the diagnostics of lung adenocarcinoma.
Department of Pathology, Center for Cancer Research and Translational Medicine, University of Oulu, POB 5000, 90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029 Oulu, Finland. Electronic address: johanna.makinen@oulu.fi.
Johanna M
JM
Mäkinen
Department of Internal Medicine, Respiratory Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029 Oulu, Finland.
Kirsi
K
Laitakari
Department of Internal Medicine, Respiratory Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029 Oulu, Finland.
Shirley
S
Johnson
Department of Internal Medicine, Respiratory Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029 Oulu, Finland.
Riitta
R
Mäkitaro
Medical Informatics and Statistics Research Group, University of Oulu, POB 5000, 90014 Oulu, Finland.
Risto
R
Bloigu
Department of Pathology, Center for Cancer Research and Translational Medicine, University of Oulu, POB 5000, 90014 Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029 Oulu, Finland.
Elisa
E
Lappi-Blanco
Department of Internal Medicine, Respiratory Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, POB 20, 90029 Oulu, Finland; Unit of Medicine and Clinical Research, Pulmonary Division, University of Eastern Finland, POB 1627, 70211 Kuopio, Finland; Center of Medicine and Clinical Research, Division of Respiratory Medicine, Kuopio University Hospital, POB 100, 70029 Kuopio, Finland.
Riitta
R
Kaarteenaho
D000230:Adenocarcinoma / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
Adenocarcinoma; Histology; Lepidic; Lung cancer; Prognosis; Subtype