Journal of Pathology and Translational Medicine

Myung-Ju Ahn

6 Articles

Molecular Screening of Small Biopsy Samples Using Next-Generation Sequencing in Korean Patients with Advanced Non-small Cell Lung Cancer: Korean Lung Cancer Consortium (KLCC-13-01): Bo Mi Ku, Mi Hwa Heo, Joo-Hang Kim, Byoung Chul Cho, Eun Kyung Cho, Young Joo Min, Ki Hyeong Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Tae Jung Kim, Ho Yun Lee, Hojoong Kim, Kyung-Jong Lee, Myung-Ju Ahn; J Pathol Transl Med. 2018;52(3):148-156. Published online March 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.03.12

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Background
Non-small cell lung cancer (NSCLC) is a common type of cancer with poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to evaluate the clinical adequacy of molecular testing using next-generation sequencing (NGS) for small biopsy samples and characterize the mutational landscape of Korean patients with advanced NSCLC.
Methods
DNA was extracted from small biopsy samples of 162 patients with advanced NSCLC. Targeted NGS of genomic alterations was conducted using Ion AmpliSeq Cancer Hotspot Panel v2.
Results
The median age of patients was 64 years (range, 32 to 83 years) and the majority had stage IV NSCLC at the time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had novel or hotspot mutations (range, 1 to 21 mutated genes). Mutations were found in 41 genes. Three of the most frequently mutated genes were TP53 (151, 93.2%), KDR (104, 64.2%), and epidermal growth factor receptor (EGFR; 69, 42.6%). We also observed coexistence of EGFR and other oncogene (such as KRAS, PIC3CA, PTEN, and STK11) mutations. Given that 69.6% (48/69) of EGFR mutant patients were treated with EGFR tyrosine kinase inhibitors, EGFR mutant status had higher prognostic ability in this study.
Conclusions
These results suggest that targeted NGS using small biopsy samples is feasible and allows for the detection of both common and rare mutations in NSCLC.

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Barbara Melosky, Kato Kambartel, Maik Häntschel, Margherita Bennetts, Dana J. Nickens, Julia Brinkmann, Antonin Kayser, Michael Moran, Federico Cappuzzo
Molecular Diagnosis & Therapy.2022; 26(1): 7. CrossRef
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Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
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Naoki Furuya, Shingo Matsumoto, Kazutaka Kakinuma, Kei Morikawa, Takeo Inoue, Hisashi Saji, Koichi Goto, Masamichi Mineshita
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Yitong Xu, Chenglong Wang, Xizi Jiang, Yao Zhang, Hongbo Su, Jun Jiang, Hongjiu Ren, Xueshan Qiu
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Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
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Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion
Quincy S. Chu
Therapeutic Advances in Medical Oncology.2020; 12: 175883591989575. CrossRef
Concomitant Mutations in EGFR 19Del/L858R Mutation and Their Association with Response to EGFR-TKIs in NSCLC Patients

Hengrui Liang, Caichen Li, Yi Zhao, Shen Zhao, Jun Huang, Xiuyu Cai, Bo Cheng, Shan Xiong, Jianfu Li, Wei Wang, Changbin Zhu, Weiwei Li, Jianxing He, Wenhua Liang
Cancer Management and Research.2020; Volume 12: 8653. CrossRef
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Hyun Min Koh, Dae Hyun Song
Thoracic Cancer.2019; 10(2): 143. CrossRef
PD-L1 expression inROS1-rearranged non-small cell lung cancer: A study using simultaneous genotypic screening ofEGFR,ALK, andROS1
Jongmin Lee, Chan Kwon Park, Hyoung-Kyu Yoon, Young Jo Sa, In Sook Woo, Hyo Rim Kim, Sue Youn Kim, Tae-Jung Kim
Thoracic Cancer.2019; 10(1): 103. CrossRef
Targeted Next-Generation Sequencing Validates the Use of Diagnostic Biopsies as a Suitable Alternative to Resection Material for Mutation Screening in Colorectal Cancer
Hersh A. Ham-Karim, Henry Okuchukwu Ebili, Kirsty Manger, Wakkas Fadhil, Narmeen S. Ahmad, Susan D. Richman, Mohammad Ilyas
Molecular Diagnosis & Therapy.2019; 23(3): 383. CrossRef
Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing
Hidenori Kage, Shinji Kohsaka, Aya Shinozaki‐Ushiku, Yoshihisa Hiraishi, Jiro Sato, Kazuhiro Nagayama, Tetsuo Ushiku, Daiya Takai, Jun Nakajima, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Takahide Nagase
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PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around
Anastasios Gkountakos, Giulia Sartori, Italia Falcone, Geny Piro, Ludovica Ciuffreda, Carmine Carbone, Giampaolo Tortora, Aldo Scarpa, Emilio Bria, Michele Milella, Rafael Rosell, Vincenzo Corbo, Sara Pilotto
Cancers.2019; 11(8): 1141. CrossRef

Metastatic Squamous Cell Carcinoma from Lung Adenocarcinoma after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy: Hyung Kyu Park, Youjeong Seo, Yoon-La Choi, Myung-Ju Ahn, Joungho Han; J Pathol Transl Med. 2017;51(4):441-443. Published online April 4, 2017; DOI: https://doi.org/10.4132/jptm.2016.10.18

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Morphologic-Molecular Transformation of Oncogene Addicted Non-Small Cell Lung Cancer
Fiorella Calabrese, Federica Pezzuto, Francesca Lunardi, Francesco Fortarezza, Sofia-Eleni Tzorakoleftheraki, Maria Vittoria Resi, Mariaenrica Tiné, Giulia Pasello, Paul Hofman
International Journal of Molecular Sciences.2022; 23(8): 4164. CrossRef
T790M mutation positive squamous cell carcinoma transformation from EGFR-mutated lung adenocarcinoma after low dose erlotinib: A case report and literature review
Yusaku Kusaba, Yuichiro Takeda, Sakurako Abe, Akinari Tsukada, Go Naka
Medicine.2022; 101(32): e29682. CrossRef
Case Report: EGFR-Positive Early-Stage Lung Adenocarcinoma Transforming to Squamous Cell Carcinoma After TKI Treatment
Jiatao Liao, Yuan Li, Chang Liu, Qianqian Long, Jialei Wang
Frontiers in Oncology.2021;[Epub] CrossRef
Squamous cell carcinoma transformation of lung adenocarcinoma after tyrosine kinase inhibitor therapy: Cytological approach
Alexandra Grosse, Claudia Grosse
Cytopathology.2020; 31(3): 232. CrossRef
Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case
Elisa Roca, Marta Pozzari, William Vermi, Valeria Tovazzi, Alice Baggi, Vito Amoroso, Daniela Nonnis, Salvatore Intagliata, Alfredo Berruti
Lung Cancer.2019; 127: 12. CrossRef
Squamous Cell Transformation of Primary Lung Adenocarcinoma in a Patient With EML4-ALK Fusion Variant 5 Refractory to ALK Inhibitors
Jay Gong, Jeffrey P. Gregg, Weijie Ma, Ken Yoneda, Elizabeth H. Moore, Megan E. Daly, Yanhong Zhang, Melissa J. Williams, Tianhong Li
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Yueqing Chen, Waiying Yvonne Tang, Xinyuan Tong, Hongbin Ji
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Size of Non-lepidic Invasive Pattern Predicts Recurrence in Pulmonary Mucinous Adenocarcinoma: Morphologic Analysis of 188 Resected Cases with Reappraisal of Invasion Criteria: Soohyun Hwang, Joungho Han, Misun Choi, Myung-Ju Ahn, Yong Soo Choi; J Pathol Transl Med. 2017;51(1):56-68. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.17

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Abstract PDF

Background
We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns.
Methods
Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3).
Results
The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121).
Conclusions
This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.

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Radiological and clinical features of screening-detected pulmonary invasive mucinous adenocarcinoma
Dae Hyeon Kim, So Young Bae, Kwon Joong Na, Samina Park, In Kyu Park, Chang Hyun Kang, Young Tae Kim
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Optimal method for measuring invasive size that predicts survival in invasive mucinous adenocarcinoma of the lung
Tomonari Oki, Keiju Aokage, Shogo Nomura, Kenta Tane, Tomohiro Miyoshi, Norihiko Shiiya, Kazuhito Funai, Masahiro Tsuboi, Genichiro Ishii
Journal of Cancer Research and Clinical Oncology.2020; 146(5): 1291. CrossRef
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Wei-Chin Chang, Yu Zhi Zhang, Eric Lim, Andrew G Nicholson
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Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases: Soomin Ahn, Soo Hyun Hwang, Joungho Han, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn, Woong-Yang Park; J Pathol Transl Med. 2016;50(4):258-263. Published online May 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.19

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Abstract PDF

Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors.
Methods
We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples.
Results
Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment.
Conclusions
NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.

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Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases: Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um; J Pathol Transl Med. 2016;50(3):197-203. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.09

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Abstract PDF

Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

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Pleural Mesothelioma: An Institutional Experience of 66 Cases: Soomin Ahn, In Ho Choi, Joungho Han, Jhingook Kim, Myung-Ju Ahn; Korean J Pathol. 2014;48(2):91-99. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.91

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Abstract PDF

Background

Malignant mesothelioma of the pleura is an aggressive tumor known to be associated with asbestos. Histological diagnosis of mesothelioma is challenging and is usually aided by immunohistochemical markers.

Methods

During an 18-year period (1995-2012), 66 patients with pleural mesothelioma were diagnosed at the Samsung Medical Center in Seoul. We reviewed hematoxylin and eosin and immunohistochemical slides of pleural mesothelioma and evaluated their pathological and clinical features.

Results

The male-to-female ratio was 1.75:1, and age of patients ranged from 28 to 80 years with an average age of 56.84 years. Twenty-two out of 66 patients underwent curative pneumonectomy. Follow-up data was available in 60 patients (90.9%), and 50 of them (83.3%) died from the disease. The average overall survival was 15.39 months. Histologically, the epithelioid type was the most common, followed by the sarcomatoid and the biphasic types. Epidemiologic information was not available in most cases, and only one patient was confirmed to have a history of asbestos exposure.

Conclusions

Malignant mesothelioma of the pleura is a fatal tumor, and the therapeutic benefit of pneumonectomy remains unproven. The combination of calretinin, Wilms tumor 1, HMBE-1, and thyroid transcription factor-1 may provide high diagnostic accuracy in diagnosing mesothelioma.

Citations

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