Lung adenocarcinoma expression profile: one more layer of heterogeneity
Authors: Elisabeth Brambilla
Journal: European Respiratory Journal (2013)

New study of gene expression profiles sheds light on the diversity and heterogeneity of lung adenocarcinoma http://ow.ly/oQys8Adenocarcinoma exhibits the highest level of heterogeneity among human tumours, with at least five patterns being admixed in the majority of them.The 2004 World Health Organization classification recognised this heterogeneity under the term of mixed type adenocarcinoma, which accounted for 85% of histopathological diagnoses by pathologists.Thus, this classification was not rewarding at the level of histogenesis, biological underlying properties and prognostic prediction.To shed light onto this obscure heterogeneity, the International Multidisciplinary Lung Adenocarcinoma Classification (International Association for the Study of Lung Cancer/European Respiratory Society/American Thoracic Society) was established by an international multidisciplinary panel of pathologists, clinicians, oncologists, pulmonologists, molecular biologists, radiologists and surgeons, with the ambitious task of discriminate five subtypes based on architectural patterns and their predominance (percentage of each in each case, a 5% increment) [1].Histological subtyping in lepidic, acinar, papillary solid and micropapillary patterns was proposed in order to increase the visibility of adenocarcinoma in the molecular arena and to establish correlation between adenocarcinoma predominant subtypes and clinico-pathological and prognostic characteristics.Therefore, this classification has important implications in the staging of tumours, introducing adenocarcinoma in situ and minimally invasive adenocarcinoma, both with 100% 5-year survival expectancy after resection.Adenocarcinoma in situ presents with pure ground-glass opacity (GGO) radiologically and an absence of histological invasion.Minimally invasive adenocarcinoma is characterised by an invasion area less than 5 mm and radiological (computed tomography scan) density on the background of GGO.This classification was also needed to provide a uniform terminology based on objective diagnostic criteria, and thus suppress the terms bronchioloalveolar carcinoma and mixed subtype adenocarcinoma, which both lack reproducibility, clinical counterparts and prognostic value.Histo-radiological correlations and surgical implications for patients management have been emphasised [1][2][3][4].Strategy for optimal approaches to diagnosis of advanced lung cancer patients on small biopsies or cytology fitting new treatment requirements was proposed.The prognostic value of this adenocarcinoma classification was internationally confirmed [4][5][6][7][8][9][10][11].In the current issue of the European Respiratory Journal, FUKUI et al. [12] report on the identification of the basal cell (BC) gene signature in lung adenocarcinoma and its prognostic value.Their data provide evidence that the BC transcriptome they previously established [13] contributes unique molecular features of airway BCs to the heterogeneity of adenocarcinoma.This subtype of lung adenocarcinoma, which expresses high levels of airway BC genes, is associated with aggressive clinical outcome.This BC transcriptome should correlate with the centrally located adenocarcinoma thought to arise from the surface or glandular epithelium of bronchi, in contrast to the terminal respiratory unit (TRU) adenocarcinoma previously