title: Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study.
abstract: BACKGROUND
  Recently, in advanced non-small cell lung cancer (NSCLC), standard chemotherapy was flanked by biological agents directed against genomic abnormalities, including EGFR and ALK alterations, that significantly improved patient outcome. Despite these achievements, tumour progression almost always occurs and a reassessment of the tumour genetic profile may contribute to modulating the therapeutic regimen. Resampling may provide tissue for additional tests to detect acquired resistance and/or new genetic alterations, but the currently available information is limited.
  
  
  METHODS
  Histological and genetic reassessments of biopsy or surgical tissue samples from 50 non-squamous NSCLC patients before and after at least one systemic treatment were performed. EGFR, KRAS, BRAF, PIK3CA and HER2 mutations were sequenced, p.T790M was identified with real-time PCR, and ALK and MET genomic alterations by fluorescence in situ hybridization.
  
  
  RESULTS
  Overall in baseline biopsies, 37/50 (74 %) tumours had genetic alterations, either single (52 %) or multiple (22 %). Among them, 16 were EGFR mutations and 6 ALK rearrangements. In the second tissue sampling, 54 % of cases had additional genomic changes, including newly acquired alterations (81 %) or losses (18 %). The commonest changes were MET amplification and p.T790M mutation. One case had a histological shift from adenocarcinoma to small cell carcinoma.
  
  
  CONCLUSIONS
  The remarkable number of molecular changes following systemic therapy and the genetic complexity of some cases underline the value of histological and molecular re-evaluation of lung cancer to tailor the most appropriate therapy during disease progression.
authors: Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
authors: S
authors: S
authors: Vatrano
authors: Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
authors: L
authors: L
authors: Righi
authors: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Hospital, Orbassano (Turin), Italy.
authors: T
authors: T
authors: Vavalá
authors: Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
authors: I
authors: I
authors: Rapa
authors: Division of Radiology, Department of Oncology, University of Turin at San Luigi Hospital, Orbassano (Turin), Italy.
authors: M
authors: M
authors: Busso
authors: Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
authors: S
authors: S
authors: Izzo
authors: Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy.
authors: S
authors: S
authors: Cappia
authors: Division of Radiology, Department of Oncology, University of Turin at San Luigi Hospital, Orbassano (Turin), Italy.
authors: A
authors: A
authors: Veltri
authors: Division of Pathology, Department of Oncology, University of Turin at San Luigi Hospital, Regione Gonzole 10, 10043, Orbassano (Turin), Italy. mauro.papotti@unito.it.
authors: M
authors: M
authors: Papotti
authors: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Hospital, Orbassano (Turin), Italy.
authors: G V
authors: GV
authors: Scagliotti
authors: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Hospital, Orbassano (Turin), Italy.
authors: S
authors: S
authors: Novello
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies