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Comparison of epidermal growth factor receptor mutation analysis results between surgically resected primary lung cancer and metastatic lymph nodes obtained by endobronchial ultrasound-guided transbronchial needle aspiration.

Thoracic Cancer 2012 August
BACKGROUND:   Lung cancers with mutations in the epidermal growth factor receptor (EGFR) gene respond well to treatment with EGFR inhibitors. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered a useful modality to obtain samples from the mediastinal and hilar lymph nodes. However, the EGFR gene status of EBUS-TBNA samples may not always match that of primary tumors.

METHODS:   In 14 node-positive patients diagnosed by EBUS-TBNA, EGFR mutation analysis results were compared between EBUS-TBNA samples and surgically removed primary tumors. EGFR mutation was screened with peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp followed by direct sequence analysis. For one controversial case, gene mutation analyses were performed for the multiple micro-fractions of a metastatic lymph node, which exhibited the heterogeneous immunohistochemical features.

RESULTS:   EBUS-TBNA diagnosed one case of exon 21 point mutations, one case of exon 19 deletion, and 12 cases of wild-type EGFR. Results were consistent with those of surgically removed primary tumors in 13 of 14 cases. One case of wild-type EGFR diagnosed by EBUS-TBNA exhibited exon 21 point mutation in the surgically removed primary tumor. The metastatic lymph node targeted by EBUS-TBNA mostly consisted of cancer cells with wild-type EGFR; however, a minor component positive for thyroid transcription factor-1 (TTF-1) and surfactant-associated protein A (PE-10) exhibited EGFR mutation.

CONCLUSION:   The combination of EBUS-TBNA and PNA-LNA clamp is useful for EGFR mutation analysis. However, EGFR mutation status in EBUS-TBNA samples may not be consistent with that of the primary tumor when the tumor contains few EGFR mutations.

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