title: The application of molecular diagnostic studies interrogating EGFR and KRAS mutations to stained cytologic smears of lung carcinoma.
abstract: EGFR and KRAS mutation analyses are of increasing importance for guiding the treatment of non-small cell lung carcinomas. Insufficient cellularity of cell blocks can represent an impediment to the performance of these tests. We investigated the usefulness of cytologic direct smears as an alternative specimen source for mutation testing. Tumor cell-enriched areas from freshly prepared and archived rapid Romanowsky-stained direct smears in 33 cases of lung carcinoma were microdissected for DNA isolation and evaluated for EGFR and KRAS mutations. EGFR mutations were detected in 3 adenocarcinomas; 2 tumors had the L858R substitution and 1 an exon 19 deletion. KRAS mutations affecting codon 12, 13, or 61 were detected in 11 cases (8 adenocarcinomas and 3 non-small cell carcinomas). EGFR and KRAS mutations were mutually exclusive. Hence, archived and freshly prepared direct smears represent a robust and valuable specimen source for molecular studies, especially when cell blocks exhibit insufficient cellularity.
authors.affiliation: Department of Pathology, University of Michigan Health System, 1500 E Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Betz
authors.forename: Michael H
authors.initials: MH
authors.lastname: Roh
authors.forename: Helmut C
authors.initials: HC
authors.lastname: Weigelin
authors.forename: Jeremiah B
authors.initials: JB
authors.lastname: Placido
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Schmidt
authors.forename: Sara
authors.initials: S
authors.lastname: Farmen
authors.forename: Doug A
authors.initials: DA
authors.lastname: Arenberg
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Kalemkerian
authors.forename: Stewart M
authors.initials: SM
authors.lastname: Knoepp
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D003584:Cytological Techniques; D004252:DNA Mutational Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D057089:Pathology, Molecular / Q000379:methods; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000032:analysis*
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins