Discordance of molecular biomarkers associated with epidermal growth factor receptor pathway between primary tumors and lymph node metastasis in non-small cell lung cancer.
BACKGROUND
For the identification of the patients who most likely benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), molecular assays are considered to be of paramount importance. Given the heterogeneity of NSCLC at the molecular level, this study was conducted to determine the discrepancy in EGFR mutations between primary tumors and the corresponding lymph node metastasis.


METHODS
Surgically resected 101 paired primary NSCLC and metastatic lymph nodes were evaluated for the EGFR mutations by direct DNA sequencing and heteroduplex analysis.


RESULTS
EGFR mutation was detected in 29.7% (30 of 101) of the primary tumors and in 27.7% of lymph node metastases (28 of 101) by either direct sequencing or heteroduplex analysis, respectively. By direct sequencing, 12 cases (11.9%) showed discordance in EGFR mutations between primary tumors and metastasis. In 11 cases, EGFR mutations were detected only in the primary tumor, whereas 1 case only in lymph node metastases. By heteroduplex analysis, 17 cases (16.8%) were discordant. Ten cases were primary tumor positive and lymph node negative, whereas seven cases were lymph node positive and primary tumor negative.


CONCLUSIONS
A considerable proportion of NSCLC showed discrepancy in EGFR mutations between primary tumors and metastatic lymph nodes, suggesting tumor heterogeneity at the molecular level during the process of metastasis.
Park
Sarah
S
Department of Medicine, Division of Hematology-Oncology, Hangang Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea.
Holmes-Tisch
Alison J
AJ
Cho
Eun Yoon
EY
Shim
Young Mog
YM
Kim
Jinkook
J
Kim
Hyo Song
HS
Lee
Jeeyun
J
Park
Yeon Hee
YH
Ahn
Jin Seok
JS
Park
Keunchil
K
Jänne
Pasi A
PA
Ahn
Myung-Ju
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016009:Chi-Square Distribution; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020180:Heteroduplex Analysis; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017422:Sequence Analysis, DNA
D014408:Biomarkers, Tumor; D066246:ErbB Receptors