The Application of Molecular Diagnostic Studies Interrogating EGFR and KRAS Mutations to Stained Cytologic Smears of Lung Carcinoma

被引:70
作者
Betz, Bryan L. [1 ]
Roh, Michael H. [1 ]
Weigelin, Helmut C. [1 ]
Placido, Jeremiah B. [1 ]
Schmidt, Lindsay A. [1 ]
Farmen, Sara [1 ]
Arenberg, Doug A. [2 ]
Kalemkerian, Gregory P. [2 ]
Knoepp, Stewart M. [1 ]
机构
[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA
[2] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA
关键词
Lung cancer; EGFR; KRAS; Cytology; Direct smear; Fine-needle aspiration; Non-small cell carcinoma; Adenocarcinoma; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; SENSITIVE METHOD; GENE-MUTATIONS; CANCER; ADENOCARCINOMA; GEFITINIB; SPECIMENS; SURVIVAL;
D O I
10.1309/AJCP84TUTQOSUONG
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
引用
收藏
页码:564 / 571
页数:8
相关论文
共 27 条
[1]   Mutational analysis in cytological specimens of advanced lung adenocarcinoma: A sensitive method for molecular diagnosis [J].
Boldrini, Laura ;
Gisfredi, Silvia ;
Ursino, Silvia ;
Camacci, Tiziano ;
Baldini, Editta ;
Melfi, Franca ;
Fontanini, Gabriella .
JOURNAL OF THORACIC ONCOLOGY, 2007, 2 (12) :1086-1090
[2]  
*COLL AM PATH, 2010, CAP 2010 KRAS A PROF
[3]   Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib [J].
Eberhard, DA ;
Johnson, BE ;
Amler, LC ;
Goddard, AD ;
Heldens, SL ;
Herbst, RS ;
Ince, WL ;
Jänne, PA ;
Januario, T ;
Johnson, DH ;
Klein, P ;
Miller, VA ;
Ostland, MA ;
Ramies, DA ;
Sebisanovic, D ;
Stinson, JA ;
Zhang, YR ;
Seshagiri, S ;
Hillan, KJ .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :5900-5909
[4]   Detection of EGFR and KRAS mutations on trans-thoracic needle aspiration of lung nodules by high resolution melting analysis [J].
Fassina, A. ;
Gazziero, A. ;
Zardo, D. ;
Corradin, M. ;
Aldighieri, E. ;
Rossi, G. P. .
JOURNAL OF CLINICAL PATHOLOGY, 2009, 62 (12) :1096-1102
[5]   Archival Fine-Needle Aspiration Cytopathology (FNAC) Samples Untapped Resource for Clinical Molecular Profiling [J].
Killian, J. Keith ;
Walker, Robert L. ;
Suuriniemi, Miia ;
Jones, Laura ;
Scurci, Stephanie ;
Singh, Parvati ;
Cornelison, Robert ;
Harmon, Shannon ;
Boisvert, Nichole ;
Zhu, Jack ;
Wang, Yonghong ;
Bilke, Sven ;
Davis, Sean ;
Giaccone, Giuseppe ;
Smith, William I., Jr. ;
Meltzer, Paul S. .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2010, 12 (06) :739-745
[6]   Molecular changes of epidermal growth factor receptor (EGFR) and KRAS and their impact on the clinical outcomes in surgically resected adenocarcinoma of the lung [J].
Kim, Young Tae ;
Kim, Tae-you ;
Lee, Dong Soon ;
Park, Sun Jung ;
Park, Ju-Yeon ;
Seo, Soon-Jung ;
Choi, Hyo-Seon ;
Kang, Hee Jung ;
Hahn, Seokyung ;
Kang, Chang Hyun ;
Sung, Sook Whan ;
Kim, Joo Hyun .
LUNG CANCER, 2008, 59 (01) :111-118
[7]  
LADANYI M, 2008, MODERN PATHOL, V21, P2
[8]   Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib [J].
Lynch, TJ ;
Bell, DW ;
Sordella, R ;
Gurubhagavatula, S ;
Okimoto, RA ;
Brannigan, BW ;
Harris, PL ;
Haserlat, SM ;
Supko, JG ;
Haluska, FG ;
Louis, DN ;
Christiani, DC ;
Settleman, J ;
Haber, DA .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (21) :2129-2139
[9]   EGFR mutations in non-small-cell lung cancer:: Analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment [J].
Marchetti, A ;
Martella, C ;
Felicioni, L ;
Barassi, F ;
Salvatore, S ;
Chella, A ;
Camplese, PP ;
Iarussi, T ;
Mucilli, F ;
Mezzetti, A ;
Cuccurullo, F ;
Sacco, R ;
Buttitta, F .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (04) :857-865
[10]   Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib [J].
Miller, Vincent A. ;
Riely, Gregory J. ;
Zakowski, Maureen F. ;
Li, Allan R. ;
Patel, Jyoti D. ;
Heelan, Robert T. ;
Kris, Mark G. ;
Sandler, Alan B. ;
Carbone, David P. ;
Tsao, Anne ;
Herbst, Roy S. ;
Heller, Glenn ;
Ladanyi, Marc ;
Pao, William ;
Johnson, David H. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (09) :1472-1478