Journal of Pathology and Translational Medicine

Original Article

KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing: Boram Lee, Boin Lee, Gangmin Han, Mi Jung Kwon, Joungho Han, Yoon-La Choi; Korean J Pathol. 2014;48(2):100-107. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.100

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Background

KRAS is one of commonly mutated genetic "drivers" in non-small cell lung cancers (NSCLCs). Recent studies indicate that patients with KRAS-mutated tumors do not benefit from adjuvant chemotherapy, so there is now a focus on targeting KRAS-mutated NSCLCs. A feasible mutation detection method is required in order to accurately test for KRAS status.

Methods

We compared direct Sanger sequencing and the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method in 134 NSCLCs and explored associations with clinicopathological factors. Next-generation sequencing (NGS) was used to validate the results of discordant cases. To increase the resolution of low-level somatic mutant molecules, PNA-mediated PCR clamping was used for mutant enrichment prior to NGS.

Results

Twenty-one (15.7%) cases were found to have the KRAS mutations using direct sequencing, with two additional cases by the PNA-mediated PCR clamping method. The frequencies of KRAS mutant alleles were 2% and 4%, respectively, using conventional NGS, increasing up to 90% and 89%, using mutant-enriched NGS. The KRAS mutation occurs more frequently in the tumors of smokers (p=.012) and in stage IV tumors (p=.032).

Conclusions

Direct sequencing can accurately detect mutations, but, it is not always possible to obtain a tumor sample with sufficient volume. The PNA-mediated PCR clamping can rapidly provide results with sufficient sensitivity.

Citations

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Brief Case Report

Micropapillary Mucinous Adenocarcinoma of the Lung: A Brief Case Report: In Ho Choi, Boin Lee, Joungho Han, Chin A Yi, Yong Soo Choi, Jin Seok Ahn; Korean J Pathol. 2013;47(6):603-605. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.603

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Citations

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Molecular Pathology of Lung Cancer
James J. Saller, Theresa A. Boyle
Cold Spring Harbor Perspectives in Medicine.2022; 12(3): a037812. CrossRef
The clinicopathological significance of ALK rearrangements and KRAS and EGFR mutations in primary pulmonary mucinous adenocarcinoma
Yang Qu, Nanying Che, Dan Zhao, Chen Zhang, Dan Su, Lijuan Zhou, Lili Zhang, Chongli Wang, Haiqing Zhang, Lixin Wei
Tumor Biology.2015; 36(8): 6417. CrossRef
Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine‐needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations
Dae Hyun Song, Boram Lee, Yooju Shin, In Ho Choi, Sang Yun Ha, Jae Jun Lee, Min Eui Hong, Yoon‐La Choi, Joungho Han, Sang‐Won Um
Diagnostic Cytopathology.2015; 43(7): 539. CrossRef

Original Article

Cytologic Features of ALK-Positive Pulmonary Adenocarcinoma: Seung Yeon Ha, Jungsuk Ahn, Mee Sook Roh, Joungho Han, Jae Jun Lee, Boin Lee, Jun Yim; Korean J Pathol. 2013;47(3):252-257. Published online June 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.252

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Abstract PDF

Background

The aim of this study was to determine the cytologic features of anaplastic lymphoma kinase (ALK) expressing pulmonary adenocarcinoma.

Methods

We analyzed the cytopathological findings of 15 cases of endobronchial ultrasound guided aspiration and a case of bronchial washing. These cases were selected based on the histomorphology of ALK-rearranged lung adenocarcinoma.

Results

Cytology showed mucinous (81.3%) and hemorrhagic (50%) backgrounds. The cells were arranged in tubulopapillary or tubulocribriform patterns (93.8%), and clusters (56.3%) admixed with signet ring cell features (87.5%). The tumor cells were monotonous and uniform with vesicular nuclei and a small nucleolus.

Conclusions

The characteristic findings were sheets showing a tubulopapillary or tubulocribriform appearance, with vesicular nuclei and a bland chromatin pattern (p<0.001). Scattered signet ring cells were helpful in suggesting ALK-positive adenocarcinoma (p<0.001).

Citations

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Cancer Cytopathology.2022; 130(10): 812. CrossRef
Fine‐needle aspiration cytology of non‐small cell lung carcinoma: A paradigm shift
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K. Miyata, S. Morita, H. Dejima, N. Seki, N. Matsutani, M. Mieno, F. Kondo, Y. Soejima, F. Tanaka, M. Sawabe
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ALK-rearranged adenocarcinoma with extensive mucin production can mimic mucinous adenocarcinoma: clinicopathological analysis and comprehensive histological comparison with KRAS-mutated mucinous adenocarcinoma
Yoon Jin Cha, Joungho Han, Soo Hyun Hwang, Tae Bum Lee, Hojoong Kim, Jea Ill Zo
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Cytomorphological identification of advanced pulmonary adenocarcinoma harboring KRAS mutation in lymph node fine‐needle aspiration specimens: Comparative investigation of adenocarcinoma with KRAS and EGFR mutations
Dae Hyun Song, Boram Lee, Yooju Shin, In Ho Choi, Sang Yun Ha, Jae Jun Lee, Min Eui Hong, Yoon‐La Choi, Joungho Han, Sang‐Won Um
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