EGFR mutations are detected comparably in cytologic and surgical pathology specimens of nonsmall cell lung cancer.
BACKGROUND
Somatic mutations in the epidermal growth factor receptor (EGFR) are present in approximately 10% of nonsmall cell lung cancers, and higher in never-smokers, women, and Asians. Small in-frame deletions in exon 19 ( approximately 45%) and L858R mutation in exon 21 ( approximately 40%) predict response to treatment with tyrosine kinase inhibitors, whereas some others herald resistance. Direct sequencing of tumor DNA detects all EGFR mutations, but is limited by interference from nonmalignant cells within the samples. Concern over such interference has discouraged testing cytologic samples, but the adequacy of cytologic specimens for EGFR sequencing has not been studied.


METHODS
EGFR sequencing of surgical and cytologic specimens at Brigham and Women's Hospital over the past 2 years was reviewed. Of 239 specimens, 227 (95%) were surgical, and 12 (5%) were cytologic (fine needle aspirations, pleural fluids, bronchial washings, and bronchoalveolar lavages).


RESULTS
Sixty-three (28%) surgical specimens showed EGFR mutations, whereas 143 (63%) were negative, 8 (3.5%) failed, and 14 (6.2%) were inconclusive (negative result in a heterogeneous sample). Seven (58%) cytologic specimens showed EGFR mutations, whereas 4 (33%) were negative, and 1 (8.3%) was inconclusive. Cytologic specimens were more likely to have a mutation than surgical specimens (P = .02). There was no significant difference in the frequency of inconclusive results.


CONCLUSIONS
Cytologic specimens are suitable for EGFR sequencing and show comparable sensitivity for mutation detection as compared with surgical specimens. The suitability of a sample should be determined on a case-by-case basis, and cytologic samples should not be dismissed as inadequate without a thorough review.
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Jason H
JH
Smouse
Edmund S
ES
Cibas
Pasi A
PA
Jänne
Victoria A
VA
Joshi
Kelly H
KH
Zou
Neal I
NI
Lindeman
D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003581:Cytodiagnosis / Q000379:methods*; D003584:Cytological Techniques; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010340:Pathology, Surgical / Q000379:methods*
D066246:ErbB Receptors