title: Histological features of malignancy correlate with growth patterns and patient outcome in lung adenocarcinoma.
abstract: OBJECTIVE
  Until the launch of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society adenocarcinoma classification in 2011, there were no uniform histological grading criteria for pulmonary adenocarcinomas. The current classification highlights the prognostic importance of the various histological growth patterns observed in these morphologically heterogeneous neoplasias. In this study, we aimed to evaluate the classic histological parameters of malignancy in correlation with the growth patterns and patient outcomes in a series of 112 surgically operated stage I-IV lung adenocarcinomas.
  
  
  RESULTS
  Architectural growth pattern analysis was performed according to the current adenocarcinoma classification. Histological features including, for example, nuclear atypia, mitotic activity, tumour necrosis, and different patterns of invasion were assessed and correlated statistically with the architecture and the clinical data. A solid predominant histology was associated with increased levels of atypia (P = 0.027), mitotic activity (P < 0.001), necrosis (P < 0.001), and lymphovascular invasion (P = 0.001), and a non-predominant solid pattern was associated with intra-alveolar tumour spread (P = 0.004). The presence of a non-predominant lepidic tumour component showed inverse correlations with atypia (P = 0.002), mitotic rate (P = 0.009), and tumour necrosis (P < 0.001). Tumour size (P < 0.001), mitotic activity (P = 0.019), tumour necrosis (P = 0.002), lymphovascular invasion (P = 0.001) and visceral pleural involvement (P = 0.001) were all associated with reduced disease-specific survival.
  
  
  CONCLUSIONS
  The classic histological features of malignancy correlate with tumour architecture and patient outcome, confirming the prognostic value of the growth pattern analysis and questioning the need for a parallel grading system in pulmonary adenocarcinoma.
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.|Medical Research Centre, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Johanna M
authors.identifier: http://orcid.org/0000-0001-6129-7272
authors.initials: JM
authors.lastname: Mäkinen
authors.affiliation: Department of Internal Medicine, Respiratory Research Unit, Medical Research Centre, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Laitakari
authors.affiliation: Department of Internal Medicine, Respiratory Research Unit, Medical Research Centre, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Shirley
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Department of Internal Medicine, Respiratory Research Unit, Medical Research Centre, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Mäkitaro
authors.affiliation: Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.affiliation: Department of Pathology, Oulu University Hospital, Oulu, Finland.
authors.forename: Paavo
authors.initials: P
authors.lastname: Pääkkö
authors.affiliation: Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.|Department of Pathology, Oulu University Hospital, Oulu, Finland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lappi-Blanco
authors.affiliation: Department of Internal Medicine, Respiratory Research Unit, Medical Research Centre, Oulu University Hospital and University of Oulu, Oulu, Finland.|Unit of Medicine and Clinical Research, Pulmonary Division, University of Eastern Finland and Centre of Medicine and Clinical Research, Division of Respiratory Medicine, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Kaarteenaho
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
keywords: growth patterns; histology; lung adenocarcinoma; lung cancer; prognosis; smoking