title: Cytomorphologic features of advanced lung adenocarcinomas tested for EGFR and KRAS mutations: a retrospective review of 50 cases.
abstract: Associations between bronchioloalveolar carcinoma (BAC), mucinous differentiation, and epidermal growth factor receptor (EGFR) and KRAS mutations have been previously reported in studies of surgical specimens. We present the cytomorphology of lung adenocarcinomas, including metastases that were diagnosed by cytologic methods and the relationship to both EGFR and KRAS mutational status. We retrospectively reviewed the clinical and cytomorphologic features of 50 lung adenocarcinomas that were tested for both EGFR and KRAS mutations. Cytomorphologic features evaluated included cell size, architectural pattern, nucleoli, intranuclear cytoplasmic inclusions (INCI), mucin, necrosis, squamoid features, lymphocytic response, and histologic features of BAC differentiation. DNA was extracted from a paraffin-embedded cell block or frozen needle core fragments. Exon 19 deletions and the L858R mutation in exon 21 of EGFR were detected using PCR followed by capillary electrophoresis for fragment sizing. KRAS mutational analysis was performed by real-time PCR using a set of seven different Taqman(r) allelic discrimination assays to detect six mutations in codon 12 and one mutation in codon 13. Six cases (12%) showed EGFR mutations, 12 (24%) showed KRAS mutations, and 38 (62%) contained neither EGFR nor KRAS mutations. The majority of patients had stage IV disease (78%); 20 samples (40%) were from metastatic sites. The presence of prominent INCI (P = 0.036), papillary fragments (P = 0.041), and histologic features of BAC on paraffin block (P = 0.039) correlated with the presence of EGFR mutations. The presence of necrosis (P = 0.030), squamoid features (P = 0.048), and poorly differentiated tumors (P = 0.025) were more likely to be identified in the KRAS positive group.
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. jonathan.d.marotti@hitchcock.org
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marotti
authors.forename: Mary C
authors.initials: MC
authors.lastname: Schwab
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: McNulty
authors.forename: James R
authors.initials: JR
authors.lastname: Rigas
authors.forename: Peter A
authors.initials: PA
authors.lastname: DeLong
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Memoli
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Padmanabhan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000368:Aged; D002466:Cell Nucleolus; D048429:Cell Size; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins