title: Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer.
abstract: BACKGROUND
  Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype.
  
  
  METHODS
  Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples.
  
  
  RESULTS
  From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR).
  
  
  CONCLUSIONS
  Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Paul A
authors: PA
authors: Vanderlaan
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Norihiro
authors: N
authors: Yamaguchi
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Erik
authors: E
authors: Folch
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: David H
authors: DH
authors: Boucher
authors: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Michael S
authors: MS
authors: Kent
authors: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Sidharta P
authors: SP
authors: Gangadharan
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Adnan
authors: A
authors: Majid
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Michael A
authors: MA
authors: Goldstein
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Mark S
authors: MS
authors: Huberman
authors: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Olivier N
authors: ON
authors: Kocher
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States. Electronic address: dbcosta@bidmc.harvard.edu.
authors: Daniel B
authors: DB
authors: Costa
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Anaplastic lymphoma kinase; Bone specimen; Core biopsy; EGFR; Epidermal growth factor receptor; Failure; KRAS; Lung cancer; Molecular testing; Never smokers; Non-small-cell lung cancer; Tumor genotype