title: The suitability of small biopsy and cytology specimens for EGFR and other mutation testing in non-small cell lung cancer.
abstract: BACKGROUND
  Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) when their tumor harbors an activating EGFR mutation. As the majority of NSCLC patients present with advanced disease, cytology and small biopsy specimens are frequently the only tissue available for mutation testing, but can pose challenges due to low tumor content. We aim to better define the suitability of these specimens for mutation testing.
  
  
  METHODS
  NSCLC cases referred to our institution for mutation testing over a 15-month period were retrospectively reviewed. Specimens were tested for mutations including EGFR, KRAS, and BRAF, using a multiplex PCR assay (OncoCarta Panel v1.0) and analyzed on the Agena Bioscience MassARRAY platform.
  
  
  RESULTS
  A total of 146 specimens were tested, comprising 53 (36.3%) resection specimens (including 28 lung resection specimens), 55 (37.7%) small biopsy specimens and 38 (26%) cytology specimens. Of 142 cases with sufficient DNA for mutation testing, EGFR mutations were detected in 31 specimens (21.8%), KRAS mutations in 31 specimens (21.8%) and BRAF mutations in three specimens (2.1%). There was no significant difference in the EGFR mutation rate between lung resection (10 of 28 cases; 35.7%), small biopsy (9 of 53 cases; 17%), and cytology specimens (8 of 36 cases; 22.2%).
  
  
  CONCLUSIONS
  Our results support the utility of small biopsy and cytology specimens for mutation testing. Careful evaluation of the adequacy of small specimens is required to minimize the risk of false negative or positive results.
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Shu
authors: S
authors: Wang
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Bing
authors: B
authors: Yu
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Chiu Chin
authors: CC
authors: Ng
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Belinda
authors: B
authors: Mercorella
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Christina I
authors: CI
authors: Selinger
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Sandra A
authors: SA
authors: O'Toole
authors: 1 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 2 Sydney Medical School, The University of Sydney, NSW 2006, Australia ; 3 Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia ; 4 The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia ; 5 School of Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
authors: Wendy A
authors: WA
authors: Cooper
keywords: Cytology; epidermal growth factor receptor mutation (EGFR mutation); lung adenocarcinoma; molecular diagnostic testing; non-small cell lung cancer (NSCLC)