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Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-Kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim
Received September 15, 2023  Accepted November 1, 2023  Published online January 10, 2024  
DOI: https://doi.org/10.4132/jptm.2023.11.01    [Epub ahead of print]
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AbstractAbstract PDF
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
Lymphoproliferative disorder involving body fluid: diagnostic approaches and roles of ancillary studies
Jiwon Koh, Sun Ah Shin, Ji Ae Lee, Yoon Kyung Jeon
J Pathol Transl Med. 2022;56(4):173-186.   Published online July 4, 2022
DOI: https://doi.org/10.4132/jptm.2022.05.16
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AbstractAbstract PDF
Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.

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  • The urgency of Burkitt lymphoma diagnosis in fluid cytology—A tertiary care experience
    Soundarya Ravi, Anu K. Devi, Prabhu Manivannan, Debasis Gochhait, Rakhee Kar, Neelaiah Siddaraju
    Cytopathology.2024; 35(2): 275.     CrossRef
  • Immunocytochemistry on frozen-embedded cell block for the diagnosis of hematolymphoid cytology specimen: a straightforward alternative to the conventional cell block
    Youjeong Seo, Sanzida Alam Prome, Lucia Kim, Jee Young Han, Joon Mee Kim, Suk Jin Choi
    Journal of Hematopathology.2024; 17(1): 1.     CrossRef
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    Kafil Akhtar, Gowthami Nagendhran, Anjum Ara, Masheera Akhtar
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DNA-protein biomarkers for immunotherapy in the era of precision oncology
Binnari Kim, So Young Kang, Kyoung-Mee Kim
J Pathol Transl Med. 2021;55(1):26-32.   Published online November 9, 2020
DOI: https://doi.org/10.4132/jptm.2020.09.23
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AbstractAbstract PDF
The use of biomarkers to guide patient and therapy selection has gained much attention to increase the scope and complexity of targeted therapy options and immunotherapy. Clinical trials provide a basis for discovery of biomarkers, which can then aid in development of new drugs. To that end, samples from cancer patients, including DNA, RNA, protein, and the metabolome isolated from cancer tissues and blood or urine, are analyzed in various ways to identify relevant biomarkers. In conjunction with nucleotide-based, high-throughput, next-generation sequencing techniques, therapy-guided biomarker assays relying on protein-based immunohistochemistry play a pivotal role in cancer care. In this review, we discuss the current knowledge regarding DNA and protein biomarkers for cancer immunotherapy

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  • Biomarkers for Predicting Response to Personalized Immunotherapy in Gastric Cancer
    Moonsik Kim, Ji Yun Jeong, An Na Seo
    Diagnostics.2023; 13(17): 2782.     CrossRef
Original Article
Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer
Hye Jung Hwang, Soo Kyung Nam, Hyunjin Park, Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Woo Ho Kim, Hye Seung Lee
J Pathol Transl Med. 2020;54(5):378-386.   Published online July 1, 2020
DOI: https://doi.org/10.4132/jptm.2020.06.01
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AbstractAbstract PDFSupplementary Material
Background
Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC.
Methods
Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC. IHC for p53 was performed and interpreted as strong, weak, or negative expression. In 18 cases (15.0%) with discrepant TP53 mutation and p53 IHC results, p53 IHC was repeated.
Results
Strong expression of p53 was associated with TP53 missense mutations, negative expression with other types of mutations, and weak expression with wild-type TP53 (p<.001). The sensitivity for each category was 90.9%, 79.0%, and 80.9%, and the specificity was 95.4%, 88.1%, and 92.3%, respectively. The TNM stage at initial diagnosis exhibited a significant correlation with both TP53 mutation type (p=.004) and p53 expression status (p=.029). The Kaplan-Meier survival analysis for 109 stage II and III GC cases showed that patients with TP53 missense mutations had worse overall survival than those in the wild-type and other mutation groups (p=.028). Strong expression of p53 was also associated with worse overall survival in comparison to negative and weak expression (p=.035).
Conclusions
Results of IHC of the p53 protein may be used as a simple surrogate marker of TP53 mutations. However, negative expression of p53 and other types of mutations of TP53 should be carefully interpreted because of its lower sensitivity and different prognostic implications.

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Case Study
Morule-like features in pulmonary adenocarcinoma associated with epidermal growth factor receptor mutations: two case reports with targeted next-generation sequencing analysis
Yoo Jin Lee, Harim Oh, Eojin Kim, Bokyung Ahn, Jeong Hyeon Lee, Youngseok Lee, Yang Seok Chae, Chul Hwan Kim
J Pathol Transl Med. 2020;54(1):119-122.   Published online November 1, 2019
DOI: https://doi.org/10.4132/jptm.2019.09.30
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AbstractAbstract PDF
Morules, or morule-like features, can be identified in benign and malignant lesions in various organs. Morular features are unusual in pulmonary adenocarcinoma cases with only 26 cases reported to date. Here, we describe two cases of pulmonary adenocarcinoma with morule-like features in Korean women. One patient had a non-mucinous-type adenocarcinoma in situ and the other had an acinarpredominant adenocarcinoma with a micropapillary component. Both patients showed multiple intra-alveolar, nodular, whorled proliferative foci composed of atypical spindle cells with eosinophilic cytoplasm. Targeted next-generation sequencing was performed on DNA extracted from formalin-fixed paraffin-embedded samples of the tumors. Results showed unusual epidermal growth factor receptor (EGFR) mutations, which are associated with drug resistance to EGFR tyrosine kinase inhibitors, revealing the importance of identifying morule-like features in pulmonary adenocarcinoma and the need for additional study, since there are few reported cases.

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  • Pulmonary adenocarcinoma in situ with morule - like components: A surgical case report
    Mitsuteru Yosida, Mitsuru Tomita, Naoya Kawakita, Teruki Shimizu, Ryou Yamada, Hiromitsu Takizawa, Hisanori Uehara
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Original Article
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
  • 7,394 View
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AbstractAbstract PDF
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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Review
Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives
Yoon Kyung Jeon, Sun Och Yoon, Jin Ho Paik, Young A Kim, Bong Kyung Shin, Hyun-Jung Kim, Hee Jeong Cha, Ji Eun Kim, Jooryung Huh, Young-Hyeh Ko
J Pathol Transl Med. 2017;51(3):224-241.   Published online May 10, 2017
DOI: https://doi.org/10.4132/jptm.2017.04.09
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AbstractAbstract PDF
Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

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