Journal of Pathology and Translational Medicine

Reviews

Exploring histological predictive biomarkers for immune checkpoint inhibitor therapy response in non–small cell lung cancer: Uiju Cho, Soyoung Im, Hyung Soon Park; J Pathol Transl Med. 2024;58(2):49-58. Published online February 26, 2024; DOI: https://doi.org/10.4132/jptm.2024.01.31

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Abstract PDF: Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.

Biomarker testing of cytology specimens in personalized medicine for lung cancer patients: Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2022;56(6):326-333. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.10.17

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Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.

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Molecular testing of cytology specimens: Issues in specimen adequacy and clinical utility
Ghulam Ghous, Komal Ijaz, Magda Esebua, Lester J. Layfield
Diagnostic Cytopathology.2024; 52(2): 123. CrossRef
The updated College of American Pathologists principles of analytic validation of immunohistochemical assays: A step forward for cytopathology
Sinchita Roy‐Chowdhuri
Cancer Cytopathology.2024;[Epub] CrossRef

The application of high-throughput proteomics in cytopathology: Ilias P. Nikas, Han Suk Ryu; J Pathol Transl Med. 2022;56(6):309-318. Published online November 9, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.30

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Abstract PDF

High-throughput genomics and transcriptomics are often applied in routine pathology practice to facilitate cancer diagnosis, assess prognosis, and predict response to therapy. However, the proteins rather than nucleic acids are the functional molecules defining the cellular phenotype in health and disease, whereas genomic profiling cannot evaluate processes such as the RNA splicing or posttranslational modifications and gene expression does not necessarily correlate with protein expression. Proteomic applications have recently advanced, overcoming the issue of low depth, inconsistency, and suboptimal accuracy, also enabling the use of minimal patient-derived specimens. This review aims to present the recent evidence regarding the use of high-throughput proteomics in both exfoliative and fine-needle aspiration cytology. Most studies used mass spectrometry, as this is associated with high depth, sensitivity, and specificity, and aimed to complement the traditional cytomorphologic diagnosis, in addition to identify novel cancer biomarkers. Examples of diagnostic dilemmas subjected to proteomic analysis included the evaluation of indeterminate thyroid nodules or prediction of lymph node metastasis from thyroid cancer, also the differentiation between benign and malignant serous effusions, pancreatic cancer from autoimmune pancreatitis, non-neoplastic from malignant biliary strictures, and benign from malignant salivary gland tumors. A few cancer biomarkers—related to diverse cancers involving the breast, thyroid, bladder, lung, serous cavities, salivary glands, and bone marrow—were also discovered. Notably, residual liquid-based cytology samples were suitable for satisfactory and reproducible proteomic analysis. Proteomics could become another routine pathology platform in the near future, potentially by using validated multi-omics protocols.

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Identification of NIFTP-Specific mRNA Markers for Reliable Molecular Diagnosis of Thyroid Tumors
So-Yeon Lee, Jong-Lyul Park, Kwangsoon Kim, Ja Seong Bae, Jae-Yoon Kim, Seon-Young Kim, Chan Kwon Jung
Endocrine Pathology.2023; 34(3): 311. CrossRef

Original Articles

Expression of specific microRNAs in tissue and plasma in colorectal cancer: Allan Fellizar, Vivencio Refuerzo, John Donnie Ramos, Pia Marie Albano; J Pathol Transl Med. 2023;57(3):147-157. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.02.19

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Abstract PDF

Background
MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker.
Methods
Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36).
Results
MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC.
Conclusions
Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.

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The Role of Extracellular Vesicles in Colorectal Cancer
Yujian Xia, Chaoran Yu, Ernest Johann Helwig, Yousheng Li
Technology in Cancer Research & Treatment.2023;[Epub] CrossRef
HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer
Yiling Li, Kexin Li, Xiaoying Lou, Yue Wu, Samuel Seery, Danfei Xu, Yuqing Pei, Benheng Qian, Yuxin Wu, Shuang Liang, Kui Wu, Wei Cui
Cancers.2023; 15(4): 1367. CrossRef
Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence
Maria Oana Săsăran, Claudia Bănescu
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Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer
Chau-Ming Kan, Xiao Meng Pei, Martin Ho Yin Yeung, Nana Jin, Simon Siu Man Ng, Hin Fung Tsang, William Chi Shing Cho, Aldrin Kay-Yuen Yim, Allen Chi-Shing Yu, Sze Chuen Cesar Wong
International Journal of Molecular Sciences.2023; 24(13): 11026. CrossRef
Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice
Serena Ascrizzi, Grazia Maria Arillotta, Katia Grillone, Giulio Caridà, Stefania Signorelli, Asad Ali, Caterina Romeo, Pierfrancesco Tassone, Pierosandro Tagliaferri
Cancers.2023; 15(15): 3930. CrossRef

Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer: Hyunseung Oh, Soon Gu Kim, Sung Uk Bae, Sang Jun Byun, Shin Kim, Jae-Ho Lee, Ilseon Hwang, Sun Young Kwon, Hye Won Lee; J Pathol Transl Med. 2022;56(1):40-47. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.07

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Abstract PDF Supplementary Material: Background
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Post-mortem assessment of vimentin expression as a biomarker for renal tubular regeneration following acute kidney injury: Juan Carlos Alvarez Moreno, Hisham F. Bahmad, Christopher A. Febres-Aldana, Andrés Pirela, Andres Azuero, Ali Salami, Robert Poppiti; J Pathol Transl Med. 2021;55(6):369-379. Published online October 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.03

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Abstract PDF

Background
Acute kidney injury (AKI) is a common cause of morbidity and mortality. It mainly targets the renal tubular epithelium with pathological changes, referred to as acute tubular injury. The latter is followed by a regenerative response that is difficult to visualize on routine hematoxylin and eosin (H&E) stains. In this study, we examined the regenerative capacity of renal tubules by correlating vimentin (VIM) immunohistochemical (IHC) expression and pathological findings of AKI and renal tubular regeneration (RTR) on H&E.
Methods
We reviewed 23 autopsies performed in the clinical setting of AKI and RTR. VIM expression was scored in the renal cortical tubular epithelium using a statistical cutoff ≥ 3% for high expression and < 3% for low expression.
Results
Of the 23 kidney tissues examined, seven (30.4%) had low VIM expression, and 16 (69.6%) had high VIM expression. Kidney tissues with evidence of AKI and RTR had significantly higher VIM expression. Renal peritubular microenvironment features showing regenerative changes on H&E were associated with high VIM expression. In the univariate model, kidney tissues with RTR were 18-fold more likely to have high VIM expression.
Conclusions
In conclusion, our findings suggest that VIM could serve as an IHC marker for RTR following AKI. However, correlation with H&E findings remains critical to excluding chronic tubular damage. Collectively, our preliminary results pave the way for future studies including a larger sample size to validate the use of VIM as a reliable biomarker for RTR.

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Characterization of macrophages in ischemia–reperfusion injury-induced acute kidney injury based on single-cell RNA-Seq and bulk RNA-Seq analysis
Qin Wang, Yuxing Liu, Yan Zhang, Siyuan Zhang, Meifang Zhao, Zhangzhe Peng, Hui Xu, Hao Huang
International Immunopharmacology.2024; 130: 111754. CrossRef

Reviews

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; J Pathol Transl Med. 2021;55(3):181-191. Published online May 11, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.23

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Abstract PDF

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

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Clinical utility of the Oncomine Dx Target Test multi‐CDx system and the possibility of utilizing those original sequence data
Ayaka Saito, Hideki Terai, Tae‐Jung Kim, Katsura Emoto, Ryutaro Kawano, Kohei Nakamura, Hideyuki Hayashi, Hatsuyo Takaoka, Akihiko Ogata, Katsuhito Kinoshita, Fumimaro Ito, Lisa Shigematsu, Masahiko Okada, Takahiro Fukushima, Akifumi Mitsuishi, Taro Shino
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Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non-Small Cell Lung Cancer: Implications for Precision Medicine
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
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FACILITATE: A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC
Anke Behnke, Anne Cayre, Giovanna De Maglio, Giuseppe Giannini, Lionel Habran, Marina Tarsitano, Massimiliano Chetta, David Cappellen, Alexandra Lespagnol, Cecile Le Naoures, Gabriella Massazza, Annarita Destro, Irina Bonzheim, Achim Rau, Achim Battmann,
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Soo Han Kim, Mi-Hyun Kim, Min Ki Lee, Jung Seop Eom
Tuberculosis and Respiratory Diseases.2023; 86(3): 176. CrossRef
Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics
Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
Diagnostics.2022; 12(2): 326. CrossRef
Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(5): 1102. CrossRef
Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2022; 56(5): 249. CrossRef
Biomarker testing of cytology specimens in personalized medicine for lung cancer patients
Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2022; 56(6): 326. CrossRef
Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
Journal of Pathology and Translational Medicine.2022; 56(6): 334. CrossRef
Lung Cancer in Korea
Sehhoon Park, Chang-Min Choi, Seung-Sik Hwang, Yoon-La Choi, Hyae Young Kim, Young-Chul Kim, Young Tae Kim, Ho Yun Lee, Si Yeol Song, Myung-Ju Ahn
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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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Abstract 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

Current status and future perspectives of liquid biopsy in non-small cell lung cancer: Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim; J Pathol Transl Med. 2020;54(3):204-212. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.27

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Abstract PDF

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management. Epidermal growth factor receptor (EGFR) ctDNA tests have been performed in routine clinical practice in advanced NSCLC patients to guide tyrosine kinase inhibitor treatment. In the near future, liquid biopsy will be a crucial prognostic, predictive, and diagnostic method in NSCLC. Here we present the current status and future perspectives of liquid biopsy in NSCLC.

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Tailored point-of-care biosensors for liquid biopsy in the field of oncology
Sima Singh, Pritam Saha Podder, Matt Russo, Charles Henry, Stefano Cinti
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Akash Bararia, Prosenjeet Chakraborty, Paromita Roy, Bitan Kumar Chattopadhay, Amlan Das, Aniruddha Chatterjee, Nilabja Sikdar
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Gabriela Fernandes, Ana Rodrigues, Cláudia Matos, Fernando Barata, Luís Cirnes, Lurdes Ferreira, José Albino Lopes, Margarida Felizardo, Paula Fidalgo, Ulisses Brito, Bárbara Parente
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Tweezer PCR: A Highly Specific Method for Accurate Identification of Low-Abundance Mutations
Shanglin Li, Yin Gu, Zhi Geng, Kaiyi Li, Yawei Hu, Qiang Liu, Rongxin Fu, Peng Liu
Analytical Chemistry.2023; 95(48): 17679. CrossRef
Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics
Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
Diagnostics.2022; 12(2): 326. CrossRef
Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(5): 1102. CrossRef
Exosomal MicroRNA Analyses in Esophageal Squamous Cell Carcinoma Cell Lines
Sora Kim, Gwang Ha Kim, Su Jin Park, Chae Hwa Kwon, Hoseok I, Moon Won Lee, Bong Eun Lee
Journal of Clinical Medicine.2022; 11(15): 4426. CrossRef
Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
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Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
Update on molecular pathology and role of liquid biopsy in nonsmall cell lung cancer
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Tumor immune response and immunotherapy in gastric cancer: Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee; J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019; DOI: https://doi.org/10.4132/jptm.2019.10.08

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Abstract PDF

Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.

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Original Article

Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma: Seung-Yeon Yoo, Ji-Ae Lee, Yunjoo Shin, Nam-Yun Cho, Jeong Mo Bae, Gyeong Hoon Kang; J Pathol Transl Med. 2019;53(5):289-297. Published online June 24, 2019; DOI: https://doi.org/10.4132/jptm.2019.06.07

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Abstract PDF Supplementary Material

Background
SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC.
Methods
We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs.
Results
A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancerspecific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022).
Conclusions
We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.

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Review

PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future: Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2019;53(4):199-206. Published online May 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.04.24; Correction in: J Pathol Transl Med 2020;54(2):196

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Abstract PDF

Blockade of the programmed cell death-1 (PD-1) axis has already been established as an effective treatment of non-small cell lung cancer. Immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) protein is the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer. Because each PD-1/PD-L1 blockade was approved together with a specific PD-L1 IHC assay used in the clinical trials, pathologists have been challenged with performing various assays with a limited sample. To provide a more unified understanding of this, several cross-validation studies between platforms have been performed and showed consistent results. However, the interchangeability of assays may be limited in practice because of the risk of misclassification of patients for the treatment. Furthermore, several issues, including the temporal and spatial heterogeneity of PD-L1 expression in the tumor, and the potential for cytology specimens to be used as an alternative to tissue samples for PD-L1 testing, have still not been resolved. In the future, one of the main aims of immunotherapy research should be to find a novel predictive biomarker for PD-1 blockade therapy and a way to combine it with PD-L1 IHC and other tests.

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Original Article

MGMT Gene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour.: Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim; Korean J Pathol. 2011;45(5):455-462.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.455

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Abstract PDF

BACKGROUND
The aim of this study was to determine whether pyrosequencing (PSQ) might be useful to achieve O6-methyl guanine methyltransferase (MGMT) promoter methylation using 1- to 13-year-old archival tissues as a clinical biomarker in routine practice.
METHODS
The study included 141 formalin-fixed paraffin-embedded (FFPE) glial tumors from the archives of the Pathology Department from 1997-2010.
RESULTS
The average percentage of methylation (MP) of the 141 cases was 14.0+/-16.8%, and methylated cases were 32.3+/-14.9%. The average MP of each year did not show a linear increasing or decreasing pattern according to the age of the FFPE block (p=0.771). The average MP of methylated glioblastomas was 35.8+/-14.7%, 31.8+/-15.5% for anaplastic astrocytomas, and 22.4+/-15.1% for astrocytoma. A tendency was observed toward an increasing pattern of average MP with World Health Organization (WHO) grade (p=0.063) in astrocytic tumors. A correlation was observed between average MP and WHO grade (p=0.038) and a bimodal distribution was observed between the methylated and unmethylated cases, using a 9% cut-off value (p<0.001).
CONCLUSIONS
The results showed that a quantitative approach for MGMT promoter methylation yielded a 100% success rate for FFPE tissues from archives. PSQ can be used in a retrospective trial, but the cut-off value and calculation method should be further validated.

Citations

Citations to this article as recorded by

Immunohistochemical Classification of Primary and Secondary Glioblastomas
Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park
Korean Journal of Pathology.2013; 47(6): 541. CrossRef

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