Journal of Pathology and Translational Medicine

Original Articles

Comparison of Direct Sequencing, PNA Clamping-Real Time Polymerase Chain Reaction, and Pyrosequencing Methods for the Detection of EGFR Mutations in Non-small Cell Lung Carcinoma and the Correlation with Clinical Responses to EGFR Tyrosin: Hyun Ju Lee, Xianhua Xu, Hyojin Kim, Yan Jin, Pingli Sun, Ji Eun Kim, Jin-Haeng Chung; Korean J Pathol. 2013;47(1):52-60. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.52

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Background

The aims of this study were to evaluate the abilities of direct sequencing (DS), peptide nucleic acid (PNA) clamping, and pyrosequencing methods to detect epidermal growth factor receptor (EGFR) mutations in formalin-fixed paraffin-embedded (FFPE) non-small cell lung carcinoma (NSCLC) samples and to correlate EGFR mutational status as determined by each method with the clinical response to EGFR tyrosine kinase inhibitors (TKIs).

Methods

Sixty-one NSCLC patients treated with EGFR TKIs were identified to investigate somatic mutations in the EGFR gene (exons 18-21).

Results

Mutations in the EGFR gene were detected in 38 of the 61 patients (62%) by DS, 35 (57%) by PNA clamping and 37 (61%) by pyrosequencing. A total of 44 mutations (72%) were found by at least one of the three methods, and the concordances among the results were relatively high (82-85%; kappa coefficient, 0.713 to 0.736). There were 15 discordant cases (25%) among the three different methods.

Conclusions

All three EGFR mutation tests had good concordance rates (over 82%) for FFPE samples. These results suggest that if the DNA quality and enrichment of tumor cells are assured, then DS, PNA clamping, and pyrosequencing are appropriate methods for the detection of EGFR mutations.

Citations

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Loss of PTEN Expression is an Independent Poor Prognostic Factor in Non-small Cell Lung Cancer.: Seol Bong Yoo, Xianhua Xu, Hyun Ju Lee, Sanghoon Jheon, Choon Taek Lee, Gheeyoung Choe, Jin Haeng Chung; Korean J Pathol. 2011;45(4):329-335.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.329

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Abstract PDF

BACKGROUND
Alterations in the phosphatase and tensin homolog (PTEN) are correlated with tumor progression. Downregulation of PTEN is related to drug resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the prognostic significance of PTEN in patients with NSCLC and its correlation with EGFR.
METHODS
Two hundred eighty eight surgically resected NSCLC samples, including 168 adenocarcinomas (ADCs), 99 squamous cell carcinomas (SCCs) and 21 other NSCLCs were analyzed for the PTEN. The results were correlated with other clinicopathological variables including EGFR amplification and mutation.
RESULTS
Loss of PTEN was detected in 42.4% of NSCLCs, specifically 28.6% of ADCs, 66.7% of SCCs, and 38.1% of others. Loss of PTEN was significantly associated with SCC, smoking, male gender, and higher stage. In a multivariate analysis, loss of PTEN was significantly associated with short progression-free survival (p=0.037). No association between PTEN and EGFR was observed.
CONCLUSIONS
These results suggest that loss of PTEN results in shorter progression-free survival in patients with NSCLC, and loss of PTEN is more associated with SCC, smoking, male gender, and higher T stage by the 7th tumor, node and metastasis staging system but not EGFR status.

Citations

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ERCC1 Predicts a Poorer Platinum-based Chemotherapy Outcome but a Better Outcome for Uracil-Tegafur in the Resected Stage I-II NSCLC.: Han Suk Ryu, Xianhua Xu, Hyojin Kim, Jong Suk Lee, Sanghoon Jheon, Jin Haeng Chung; Korean J Pathol. 2011;45(1):45-52.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.45

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Abstract PDF: BACKGROUND
The role of excision repair cross-complementation group 1 (ERCC1) has been controversial in non-small cell lung cancer (NSCLC) patients who received adjuvant chemotherapy with a platinum agent. We investigated ERCC1 expression in stage I-II NSCLC to clarify its significance for adjuvant chemotherapy.
METHODS
The ERCC1 expression profile was evaluated by immunohistochemistry and compared according to adjuvant chemotherapeutic agents in 146 patients who underwent surgical resection for stage I-II NSCLC. The patients were divided into 3 groups; adjuvant chemotherapy with a platinum based agent (18.5%, 27/146); adjuvant chemotherapy with uracil-tegafur (UFT) (40.4%, 59/146); surgery-alone (41.1%, 60/146).
RESULTS
Nuclear ERCC1 expression was detected in 71.9% (105/146) of NSCLC and was significantly associated with a shortened survival period in the group 1 patients who received the platinum based regimen after surgery. The group 2 patients who received UFT showed the longest survival period, followed by the surgery-alone group (overall survival, p=0.049; disease-free survival [DFS], p<0.001).
CONCLUSIONS
These results suggest that stage I-II NSCLC patients with ERCC1 expression experience a shorter DFS period with adjuvant chemotherapy with a platinum based regimen and may benefit from adjuvant chemotherapy with UFT, instead of platinum after surgery.

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