An alternative approach to determining therapeutic choices in advanced non-small cell lung carcinoma (NSCLC): maximizing the diagnostic procedure and the use of low-volume lung biopsies.
BACKGROUND
Accurate mutational analysis, especially epidermal growth factor receptor (EGFR) mutations, of diagnostic biopsies from all Asian NSCLC patients is crucial to their clinical management, but faces problems. Here, we explore, within usual hospital constraints, the practicalities of incorporating mutational analysis in every newly diagnosed case of NSCLC, namely, maximizing tissue acquisition during the diagnostic procedure and determining the maximum quantity and quality of DNA sequence data available from these biopsies.


METHODS
Sixty-eight Chinese patients were enrolled. Thirty-five underwent surgical resections for early-stage tumors. Thirty-three underwent diagnostic procedures, i.e., needle aspirates under bronchoscopic or computed tomographic/fluoroscopic guidance, or forceps biopsies via bronchoscopy. Separate samples for research purposes were obtained from these 33 patients during the diagnostic procedure. All samples were analyzed for mutations in EGFR exons 18 to 21, p53 exons 4 to 9, and Kras exon 2.


RESULTS
No deaths occurred in this study. Success rates in obtaining sequence data from surgical samples versus low-volume samples for EGFR, p53, and Kras were 100% versus 85%, 100% versus 82%, and 100% versus 85%, respectively. Sequencing nine polymerase chain reaction products from each low-volume sample resulted in the exhaustion of all extracted DNA from three samples.


CONCLUSIONS
Acquiring a separate low-volume lung biopsy sample for mutational analysis in lung cancer patients during the diagnostic procedure is feasible and may be a valuable complement to the usual diagnostic workflow in future.
Lim
Elaine H
EH
Division of Oncology, Department of Medicine, National University of Singapore, Singapore. mdclime@nus.edu.sg
Zhang
Shen-Li
SL
Yu
Kun
K
Nga
Min-En
ME
Ahmed
Dokeu A
DA
Agasthian
Thirugananam
T
Wong
Poo-Sing
PS
Chua
Gim-Chuah
GC
Wong
Daniel
D
Tan
Lenny
L
Seto
Kar-Yin
KY
Yap
Wee-See
WS
Low
Seow-Ping
SP
Khoo
Kay-Leong
KL
Chang
Alex
A
Ng
Alan
A
Tan
Patrick
P
D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy / Q000379:methods*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D016009:Chi-Square Distribution; D019411:Clinical Laboratory Techniques; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012846:Singapore
D014408:Biomarkers, Tumor