Journal of Pathology and Translational Medicine

Review

Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation: Kyu Sang Lee, Gheeyoung Choe; J Pathol Transl Med. 2021;55(3):163-170. Published online April 7, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.22

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Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

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Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP
Antonio López-Beltrán, Pilar González-Peramato, Julián Sanz-Ortega, Juan Daniel Prieto Cuadra, Isabel Trias, Rafael J. Luque Barona, María Eugenia Semidey, Pablo Maroto, Ferran Algaba
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Systemic treatment of advanced and metastatic urothelial cancer: The landscape in Australia
Howard Gurney, Timothy D. Clay, Niara Oliveira, Shirley Wong, Ben Tran, Carole Harris
Asia-Pacific Journal of Clinical Oncology.2023; 19(6): 585. CrossRef
PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays
Harriet Evans, Brendan O’Sullivan, Frances Hughes, Kathryn Charles, Lee Robertson, Philippe Taniere, Salvador Diaz-Cano
Pathology and Oncology Research.2022;[Epub] CrossRef
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Original Articles

Reclassification of Mongolian Diffuse Gliomas According to the Revised 2016 World Health Organization Central Nervous System Tumor Classification: Enkhee Ochirjav, Bayarmaa Enkhbat, Tuul Baldandorj, Gheeyoung Choe; J Pathol Transl Med. 2019;53(5):298-307. Published online August 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.07.15

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Abstract PDF

Background
The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas.
Methods
A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis.
Results
According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDH^mut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDH^mut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDH^mut, 11 diffuse astrocytoma, IDH^wt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDH^mut, eight anaplastic astrocytoma, IDH^wt, NOS; and 35 glioblastoma, IDH^wt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDH^mut and 1p/19q co-deleted and diffuse astrocytoma IDH^mut showed significantly higher survival than those with diffuse astrocytoma IDH^wt, NOS (p<.01).
Conclusions
Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.

Citations

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Targeted next‐generation sequencing of adult gliomas for retrospective prognostic evaluation and up‐front diagnostics
J. K. Petersen, H. B. Boldt, M. D. Sørensen, S. Blach, R. H. Dahlrot, S. Hansen, M. Burton, M. Thomassen, T. Kruse, F. R. Poulsen, L. Andreasen, H. Hager, B. P. Ulhøi, S. Lukacova, G. Reifenberger, B. W. Kristensen
Neuropathology and Applied Neurobiology.2021; 47(1): 108. CrossRef

Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases: Kyu Sang Lee, Soo Kyung Nam, Jiwon Koh, Duck-Woo Kim, Sung-Bum Kang, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee; J Pathol Transl Med. 2016;50(4):270-277. Published online May 31, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.19

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Abstract PDF

Background
The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis.
Methods
miR-21 expression was investigated by using locked nucleic acid– fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry.
Results
The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1–4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041).
Conclusions
miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.

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Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma
Václav Mandys, Alexey Popov, Robert Gürlich, Jan Havránek, Lucie Pfeiferová, Michal Kolář, Jana Vránová, Karel Smetana, Lukáš Lacina, Pavol Szabo
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MicroRNAs and colorectal cancer: clinical potential and regulatory networks
George Yiadom Osei, Joseph Adu-Amankwaah, Selina Koomson, Solomon Beletaa, Emmanuel Akomanin Asiamah, Cecilia Smith-Togobo, Siti Razila Abdul Razak
Molecular Biology Reports.2023; 50(11): 9575. CrossRef
MicroRNA-552 expression in colorectal cancer and its clinicopathological significance
Joon Im, Soo Kyung Nam, Hye Seung Lee
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Masahiro Fukada, Nobuhisa Matsuhashi, Takao Takahashi, Nobuhiko Sugito, Kazuki Heishima, Kazuhiro Yoshida, Yukihiro Akao
Cancer Science.2021; 112(10): 4270. CrossRef
Differential expression of microRNAs in colorectal cancer: Different patterns between isolated cancer gland and stromal cells
Ayaka Sato, Yasuko Fujita, Koki Otsuka, Akira Sasaki, Hiromu Suzuki, Takayuki Matsumoto, Tamotsu Sugai
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High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment
Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim
Cancer Research and Treatment.2020; 52(1): 98. CrossRef
Tumor Tissue MIR92a and Plasma MIRs21 and 29a as Predictive Biomarkers Associated with Clinicopathological Features and Surgical Resection in a Prospective Study on Colorectal Cancer Patients
Masahiro Fukada, Nobuhisa Matsuhashi, Takao Takahashi, Nobuhiko Sugito, Kazuki Heishima, Yukihiro Akao, Kazuhiro Yoshida
Journal of Clinical Medicine.2020; 9(8): 2509. CrossRef
The promising role of noncoding RNAs in cancer-associated fibroblasts: an overview of current status and future perspectives
Zengli Fang, Jin Xu, Bo Zhang, Wei Wang, Jiang Liu, Chen Liang, Jie Hua, Qingcai Meng, Xianjun Yu, Si Shi
Journal of Hematology & Oncology.2020;[Epub] CrossRef
Altered miR-21, miRNA-148a Expression in Relation to KRAS Mutation Status as Indicator of Adenoma-Carcinoma Transitional Pattern in Colorectal Adenoma and Carcinoma Lesions
Somayeh Igder, Javad Mohammadiasl, Pooneh Mokarram
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Adewale Oluwaseun Fadaka, Babajide A. Ojo, Olusola Bolaji Adewale, Temitope Esho, Ashley Pretorius
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Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts
Fengming Yang, Zhiqiang Ning, Ling Ma, Weitao Liu, Chuchu Shao, Yongqian Shu, Hua Shen
Molecular Cancer.2017;[Epub] CrossRef
Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in stage II and III gastric cancer patients
Jiwon Koh, Chan-Young Ock, Jin Won Kim, Soo Kyung Nam, Yoonjin Kwak, Sumi Yun, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee
Oncotarget.2017; 8(16): 26356. CrossRef

Expression of c-MET in Invasive Meningioma: Sumi Yun, Jae Moon Koh, Kyu Sang Lee, An Na Seo, Kyung Han Nam, Gheeyoung Choe; J Pathol Transl Med. 2015;49(1):44-51. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.13

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Abstract PDF

Background
Meningiomas show high recurrence rates even after curative tumor removal. The invasiveness of meningiomas may contribute to their high recurrence rates. Recently, c-MET and hepatocyte growth factor (HGF) have been reported to be involved in cancer invasion. Methods: We examined the immunohistochemical expression of c-MET and HGF in 100 cases of patients with meningiomas who have undergone complete tumor removal. Results: c-MET^-High and HGFHigh were found in 17% and 13% of meningiomas, respectively. Brain invasion was observed in 17.6% of c-MET^-High meningiomas, but in only 2.4% of c-MET^-Low meningiomas (p=.033). Bone/ soft tissue invasion was observed in 23.5% of c-MET^-High meningiomas and in 9.6% of c-MET^-Low meningiomas (p=.119). HGF^-High did not show statistical association with brain invasion or bone/ soft tissue invasion. c-MET^-High demonstrated shorter recurrence-free survival (RFS, 93.5±8.2 months vs 96.1±1.9 months); however, this difference was not statistically significant (p=.139). There was no association of HGF^-High with RFS. Conclusions: This study demonstrates that c- MET^-High is associated with brain invasion of meningiomas, and that c-MET expression may be a useful predictive marker for meningioma recurrence. Patients with invasive meningiomas with high expressions of c-MET may be good candidates for targeted therapy using c-MET inhibitors.

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Curcumin Inhibits HGF-Induced EMT by Regulating c-MET-Dependent PI3K/Akt/mTOR Signaling Pathways in Meningioma
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Alborz Adeli, Katharina Hess, Christian Mawrin, Eileen Maria Susanne Streckert, Walter Stummer, Werner Paulus, André Kemmling, Markus Holling, Walter Heindel, Rene Schmidt, Dorothee Cäcilia Spille, Peter B. Sporns, Benjamin Brokinkel
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Letter: Brain Invasion in Meningiomas—Sex-Associated Differences are not Related to Estrogen- and Progesterone Receptor Expression
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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 J Pathol. 2013;47(6):541-548. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.541

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Abstract PDF

Background

Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.

Methods

We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.

Results

According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.

Conclusions

We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

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Case Report

Liquid-Based Cytology of Villoglandular Adenocarcinoma of the Cervix: A Report of 3 Cases: Younghwa Choi, Haeryoung Kim, Haiyoung Choi, Daehyun Hwang, Gheeyoung Choe, Jin-Haeng Chung, So Yeon Park, Hye Seung Lee, Jin Ho Paik, Hyo Jin Park; Korean J Pathol. 2012;46(2):215-220. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.215

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Abstract PDF

Villoglandular adenocarcinoma (VGA) is a rare subtype of cervical adenocarcinoma with a more favorable prognosis compared to conventional adenocarcinomas. Although the tumors are usually recognized on colposcopic examination due to the mainly exophytic growth pattern, they may be underdiagnosed as benign lesions by cytology because of their minimal cytologic atypia. We report the liquid-based cytology (LBC) findings of three histologically confirmed VGAs which we have recently identified. They were characterized by hypercellular smears on low-power examination with smooth-bordered three-dimensional papillary fragments. The nuclei were relatively uniform with irregular nuclear membranes. Nucleoli were small but distinct and macronucleoli were also seen. The abnormal architectural patterns such as papillary structures and nuclear overlapping and nuclear hyperchromasia are important clues to the diagnosis of VGA. In addition, nuclear membrane irregularity and prominent nucleoli can be recognized on LBC specimens, further facilitating its diagnosis.

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Annales de Pathologie.2016; 36(3): 192. CrossRef

Original Articles

Chemotherapy-Associated Hepatopathy in Korean Colorectal Cancer Liver Metastasis Patients: Oxaliplatin-Based Chemotherapy and Sinusoidal Injury: Soo Jeong Nam, Jai Young Cho, Hye Seung Lee, Gheeyoung Choe, Ja June Jang, Yoo-Seok Yoon, Ho-Seong Han, Haeryoung Kim; Korean J Pathol. 2012;46(1):22-29. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.22

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Abstract PDF

Background

Although chemotherapy-related hepatic injury has been reported in colorectal cancer liver metastasis (CRLM) patients, the morphologic changes caused by chemotherapeutic agents and the effect of chemotherapy on postoperative outcome remain ill-defined. A comprehensive review of the morphologic changes in the post-chemotherapy non-neoplastic liver was performed and the clinical effect of preoperative chemotherapy in CRLM patients was analyzed.

Methods

Hematoxylin-eosin, Masson's trichrome and reticulin-stained slides from non-neoplastic livers obtained from 89 CRLM patients were analyzed, and the clinicopathologic features were correlated with the status of chemotherapy exposure.

Results

Histopathologic features of sinusoidal injury (sinusoidal dilatation, centrilobular perivenular fibrosis, parenchymal extinction lesions, small vessel obliteration, and hepatocyte plate disruption) were significantly more frequent in oxaliplatin-exposed livers (p<0.05). The extent of sinusoidal dilatation was positively correlated with increasing numbers of chemotherapy cycles (p=0.022). Abnormal preoperative liver function tests were more frequently seen (p<0.05) and postoperative total bilirubin was higher in the chemotherapy group (p=0.008). Postoperative morbidity was more common in the chemotherapy group (p=0.044).

Conclusions

Sinusoidal injury is frequently seen in oxaliplatin-treated livers, and its presence, especially when extensive, should be documented in surgical pathology practice. The recognition of sinusoidal injury may provide helpful guidelines for surgeons in deciding the extent of hepatic resection.

Citations

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Model establishment and microarray analysis of mice with oxaliplatin‑induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
Molecular Medicine Reports.2022;[Epub] CrossRef
Oxaliplatin-induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
Toxicology.2021; 460: 152882. CrossRef
Hepatic steatosis in patients undergoing resection of colorectal liver metastases: A target for prehabilitation? A narrative review
D.T. Doherty, P.O. Coe, L. Rimmer, S. Lapsia, A. Krige, D.A. Subar
Surgical Oncology.2019; 30: 147. CrossRef
Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer
Jeonghyun Kang, Joon Seong Park, Sung Gwe Ahn, Jin Hong Lim, Seung Hyuk Baik, Dong Sup Yoon, Kang Young Lee, Joon Jeong
Annals of Surgical Treatment and Research.2018; 95(3): 161. CrossRef
Use of Imaging to Predict Complete Response of Colorectal Liver Metastases after Chemotherapy: MR Imaging versus CT Imaging
Min Jung Park, Nurhee Hong, Kyunghwa Han, Min Ju Kim, Yoon Jin Lee, Yang Shin Park, Sung Eun Rha, Sumi Park, Won Jae Lee, Seong Ho Park, Chang Hee Lee, Chung Mo Nam, Chansik An, Hye Jin Kim, Honsoul Kim, Mi-Suk Park
Radiology.2017; 284(2): 423. CrossRef
Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases
J Zhao, K M C van Mierlo, J Gómez-Ramírez, H Kim, C H C Pilgrim, P Pessaux, S S Rensen, E P van der Stok, F G Schaap, O Soubrane, T Takamoto, L Viganò, B Winkens, C H C Dejong, S W M Olde Damink, I García Sanz, E Martín Pérez, J Y Cho, Y R Choi, W Phillip
British Journal of Surgery.2017; 104(8): 990. CrossRef
Hepatic Lesions that Mimic Metastasis on Radiological Imaging during Chemotherapy for Gastrointestinal Malignancy: Recent Updates
Sung-Hye You, Beom Jin Park, Yeul Hong Kim
Korean Journal of Radiology.2017; 18(3): 413. CrossRef
Changes in Noninvasive Liver Fibrosis Indices and Spleen Size During Chemotherapy
Sehhoon Park, Hwi Young Kim, Haeryoung Kim, Jin Hyun Park, Jung Ho Kim, Ki Hwan Kim, Won Kim, In Sil Choi, Yong Jin Jung, Jin-Soo Kim
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Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: Report of five cases
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Sinusoidal obstruction syndrome after oxaliplatin-based chemotherapy
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Clinical and Molecular Hepatology.2014; 20(1): 81. CrossRef
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Xuchen Zhang, Jie Ouyang, Swan N. Thung
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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.

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Biomedicine & Pharmacotherapy.2024; 173: 116275. CrossRef
Alterations in the PI3K Pathway Drive Resistance to MET Inhibitors in NSCLC Harboring MET Exon 14 Skipping Mutations
Philippe Jamme, Marie Fernandes, Marie-Christine Copin, Clotilde Descarpentries, Fabienne Escande, Angela Morabito, Valérie Grégoire, Matthieu Jamme, Simon Baldacci, David Tulasne, Zoulika Kherrouche, Alexis B. Cortot
Journal of Thoracic Oncology.2020; 15(5): 741. CrossRef
PTEN Tumor-Suppressor: The Dam of Stemness in Cancer
Francesca Luongo, Francesca Colonna, Federica Calapà, Sara Vitale, Micol E. Fiori, Ruggero De Maria
Cancers.2019; 11(8): 1076. CrossRef
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
PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature
Jian Xiao, Cheng-Ping Hu, Bi-Xiu He, Xi Chen, Xiao-Xiao Lu, Ming-Xuan Xie, Wei Li, Shu-Ya He, Shao-Jin You, Qiong Chen
Oncotarget.2016; 7(36): 57832. CrossRef
Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment
Seol Bong Yoo, Yu Jung Kim, Hyojin Kim, Yan Jin, Ping-Li Sun, Sanghoon Jheon, Jong Seok Lee, Jin-Haeng Chung
Annals of Surgical Oncology.2013; 20(S3): 545. CrossRef
High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas
Ping‐Li Sun, Yan Jin, Hyojin Kim, Choon‐Taek Lee, Sanghoon Jheon, Jin‐Haeng Chung
Cancer Cytopathology.2013; 121(6): 311. CrossRef
Impact of HER2 and PTEN Simultaneous Deregulation in Non-small Cell Lung Carcinoma: Correlation with Biological Behavior
Ioannis Panagiotou, Stavros N. Georgiannos, Evangelos Tsiambas, Andreas Karameris, Marios Konstantinou, Andreas C. Lazaris, Nikolaos Kavantzas, George Vilaras, Efstratios Patsouris
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Expression of the Mammalian Target of Rapamycin Pathway Markers in Lung Adenocarcinoma and Squamous Cell Carcinoma
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Immunohistochemical and Molecular Characteristics of Follicular Patterned Thyroid Nodules with Incomplete Nuclear Features of Papillary Thyroid Carcinoma.: Hye Sook Min, Gheeyoung Choe, Nam Yun Cho, Gyeong Hoon Kang, Seong Hoe Park, So Yeon Park; Korean J Pathol. 2009;43(6):495-502.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.6.495

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Abstract PDF

BACKGROUND
Follicular patterned thyroid nodules with incomplete nuclear features of papillary thyroid carcinoma (FTN-INPTCs) are difficult to diagnose, and their biological behavior and association with follicular variants of PTC (FVPTCs) have not yet been established. The aim of this study is to determine immunohistochemical and molecular characteristics of FTN-INPTCs. METHODS: We investigated immunohistochemical features (galectin-3, HBME-1, CK19, fibronectin-1, CITED1), BRAF V600E mutation and RASSF1A promoter methylation status in 30 FTN-INPTC cases, along with 26 FVPTCs, 21 follicular adenomas (FAs) and 14 nodular hyperplasias (NHs). RESULTS: Expression of galectin-3, HBME-1, CK19 and CITED1 was significantly higher in FTN-INPTCs than in FAs or NHs, but expression of galectin-3, CK19 and fibronectin-1 was lower in FTN-INPTCs than in FVPTCs. The BRAF V600E mutation was not detected in the benign nodules or FTN-INPTCs, whereas 57% of FVPTCs had the mutation. RASSF1A promoter methylation was higher in FTN-INPTCs than in benign nodules but there was no difference between FTN-INPTCs and FVPTCs. CONCLUSIONS: Our results represent the borderline immunohistochemical and molecular characteristics of FTN-INPTC. We conclude that FTN-INPTC is an intermediate lesion between a benign nodule and a FVPTC, and that it is pathogenetically related to FVPTC.

Citations

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A Case of Multifocal Papillary Thyroid Carcinoma Consisting of One Encapsulated Follicular Variant withBRAFK601E Mutation and Three Conventional Types withBRAFV600E Mutation
Wook Youn Kim, Young Sin Ko, Tae Sook Hwang, Hye Seung Han, So Dug Lim, Wan Seop Kim, Seo Young Oh
Korean Journal of Pathology.2013; 47(3): 293. CrossRef
The Frequency ofBRAFMutation in Very Small Papillary Thyroid Carcinomas
Taeeun Kim, Ji-Hyun Roh, Hee-Jung Park, Jee Eun Kwon, So-Young Kang, Yoon-La Choi, Young Lyun Oh
The Korean Journal of Pathology.2010; 44(3): 308. CrossRef

Malignant Mesothelioma in Body Fluids: with Special Reference to Differential Diagnosis from Metastatic Adenocarcinoma.: Jin Ho Paik, Jin Haeng Chung, Baek Hui Kim, Gheeyoung Choe; Korean J Pathol. 2009;43(5):458-466.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.458

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Abstract PDF: BACKGROUND
Malignant mesothelioma (MM) is a rare malignant neoplasm occurring in pleura, pericardium, and peritoneum. The differential diagnosis between MM and metastatic adenocarcinoma (MA) causes diagnostic, staging, and therapeutic dilemmas. Herein, we investigated characteristic cytologic features of MM.
METHODS
Cytologic specimens of MM (n=10), MA (n=25), and reactive mesothelial hyperplasia (n=10) were retrieved and reviewed from archival materials in the Department of Pathology, Seoul National University Bundang Hospital from May 2003 to July 2008.
RESULTS
MM showed tumor cell clusters and singly scattered malignant tumor cells forming single cell populations with sparse reactive benign mesothelial cells. In contrast, MA showed distinct two cell populations of tumor cell clusters and scattered reactive mesothelial cells. Furthermore, MM frequently exhibited a characteristic long chain-like arrangement (hand-in-hand appearance) and intercellular windows, which were rarely evident in MA. Variable nuclear size, relatively consistent nuclear-cytoplasmic ratio, bior multi-nucleation, and lacy cytoplasmic borders were also frequently observed in MM.
CONCLUSIONS
Differential diagnosis of MM from MA in body fluids is possible based on meticulous examination of certain cytologic parameters, which could have significant implications in staging and treatment.

Pathological Analysis of Post-Transplantation Endomyocardial Biopsies.: Jaegul Chung, Soonae Oak, Gheeyoung Choe, Gyungyub Gong, Jooryung Huh, Eunsil Yu, Inchul Lee, Meong Gun Song, Kwang Hyun Sohn, Jae Joong Kim, Jong Goo Lee; Korean J Pathol. 1995;29(4):431-441.

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Abstract PDF: Heart transplantation was first performed in 1967. It is now regarded as a well-established treatment modality for end-stage cardiac diseases. Once the transplantation is performed, endomyocardial biopsy(EMB) is the examination of choice in monitoring the transplanted heart. We analyzed the pathological findings of follow-up EMB of 6 heart transplant patients. All patients have been suffered from severe heart failure. Four patients were adult male and two were adult females. All the hearts, except for one, displayed characteristic features of dilated cardiomyopathy. The remaining heart was diagnosed as having giant cell myocarditis. Post-transplantion EMBs were performed according to the protocol and standard cardiac biopsy grading of ISHT (1990). The standards were applied for grading of cellular rejection. In five patients, there were one or two episodes of biopsy proven acute rejection, grade II or IIIA without any clinical symptoms of rejection. Immediate "pulse therapy" was performed and follow-up biopsies were done. All episodes of rejection were cleared in subsequent biopsies. All patients are doing well without evidence of cardiac problem. The postoperative monitoring of acute rejection is critical since clinical signs of rejection are usually absent. At present, EMB is regarded as the most reliable method for diagnosis and grading of acute rejection and is an efficient guide to the monitoring of the cardiac recipients. Our experience of post-transplantation EMB corresponds with previously published reports.

Pathologic Analysis of 2159 Cases of Appendix.: Chan Sik Park, Mee Soo Chang, In Ae Park, Yong Il Kim, Gheeyoung Choe; Korean J Pathol. 2000;34(1):39-49.

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Abstract PDF: We reviewed 2159 consecutive cases of surgically resected appendices. The appendectomy specimen consisted of 91 cases of acute focal appendicitis (5.4%), 926 cases of acute suppurative appendicitis (55.1%), 228 cases of acute gangrenous appendicitis (13.6%), 63 cases of periappendicitis (3.8%), 13 cases of pure fibrous obliteration of the lumen (FOL; 0.8%), 18 cases of other diseases (7 mucoceles, 2 mucinous cystic neoplasms, 4 carcinoids, 2 metastatic carcinomas, 2 tuberculous appendicitides, and 1 eosinophilic appendicitis; 1%), and 342 cases with no diagnostic abnormality (20.3%). Patients having acute appendicitis ranged from 3 to 84 years of age, and patients in their 10's and 20's occupied over half of 2159 cases. Diagnostic accuracy of the acute appendicitis was 79.7%. Incidence of the acute appendicitis was suspected to be 7.2/100,000/year. Twenty eight cases of acute appendicitis were associated with diverticula. In the former acute primary diverticulitis led to acute appendicitis in 14 of 28 cases. Among 478 incidental appendectomy cases, there were 3 acute focal appendicitides, 1 acute suppurative appendicitis, 1 eosinophilic appendicitis, 32 periappendicitides, 1 mucocele, 40 pure FOLs, 1 deciduosis, 1 endometriosis, and 1 diverticulosis without inflammation. There were 69 cases of FOL (32 complete forms and 37 incomplete forms), among which 13 cases were associated with acute appendicitis. FOL was more frequent in female patients as well as patients over 40 years of age. Incomplete FOL was considered to progress to complete form with age. The incidence of appendiceal diverticula was higher, whereas the incidences of carcinoid tumor and FOL were lower compared with that in the western report. In 14 of 28 cases the appendiceal diverticulum was the site in which acute appendicitis began.

Cytologic Features of Primary Tumors in Central Nervous System.: Soonae Oak, Jaegul Chung, Gyungyub Gong, Gheeyoung Choe, Eunsil Yu, Inchul Lee; Korean J Cytopathol. 1994;5(2):90-98.

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Abstract PDF: There has been a marked increase in the utility of aspiration cytology for pathologic diagnosis. It may be applied to any kinds of organs and substitutes surgical biopsy. Because of the high risk of complication and difficulties in localization, aspiration cytology in the central nervous system(CNS) has been used with less frequency compared to other sites. However, with the advent of sophisticated imaging instruments, aspiration cytology of lesions in the CNS is being used increasingly. Cytologic features of the CNS neoplasms were quite similar to those of histology except one spindle cell tumor. Reviewing various CNS neoplasms, it appears that cytology may be a useful diagnostic method.

The Prognostic Significance of Neuroendocrine Differentiation for Treating Prostatic Carcinoma in 699 Cases of Radical Prostatectomy.: Tae Hoon Kang, Eun Shin, Baek Hee Kim, Gheeyoung Choe; Korean J Pathol. 2008;42(6):381-388.

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Abstract PDF: BACKGROUND
Neuroendocrine differentiation of prostatic carcinoma is known to be associated with a poor prognosis, tumor progression and androgen-independency, and there is currently no successful therapy for this type of tumor. The purpose of this study is to evaluate the prognostic implications of neuroendocrine differentiation in prostatic carcinoma in Korean men. METHODS: Six hundreds and ninety nine consecutive cases of radical prostatectomy specimens were systematically processed for topographic mapping. Neuroendocrine differentiation was detected by immunohistochemistry by using antibody to chromogranin. We analyzed the relationship between neuroendocrine differentiation and the clinicopathological prognostic factors, as well as biochemical failure. The neuroendocrine differentiation was evaluated according to the presence of chromogranin-positive cells, the pattern of neuroendocrine cells and the number of neuroendocrine cells, respectively.
RESULTS
Neuroendocrine differentiation was detected in 150 out of 699 cases (21.5%). The presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells was correlated with biochemical failure and the other clinicopathological prognostic factors such as the Gleason score, the pathologic stage, the tumor volume, angiolymphatic invasion, perineural invasion, and the Ki-67 proliferative index (p<0.05). CONCLUSIONS: We suggest that neuroendocrine differentiation of prostatic carcinoma is a prognostic factor even in radical prostatectomy specimens for localized prostate cancer. Evaluation of the presence of neuroendocrine differentiation as well as the pattern of neuroendocrine cells is recommended in radical prostatectomy specimens.

Pathological Analysis of 1,000 Cases of Transrectal Ultrasoundguided Systematic Prostate Biopsy: Establishment of New Sample Processing Method and Diagnostic Utility of Immunohistochemistry.: Chang Lim Hyun, Hee Eun Lee, Haeryung Kim, Hye Seung Lee, So Yeon Park, Jin Haeng Chung, Gheeyoung Choe; Korean J Pathol. 2006;40(6):406-419.

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Abstract PDF: BACKGROUND
We developed a new processing method for extended prostate needle biopsy, and evaluated diagnostic utility of routine immunohistochemistry in 1,000 consecutive unselected cases of transrectal ultrasound-guided systematic prostate biopsy.
METHODS
Four to five biopsy cores were embedded in one paraffin block. All the biopsy cores were immunohistochemically stained with basal cell markers.
RESULTS
The new sample processing method was technically perfect for making a diagnosis from extended prostate needle biopsy. Among 1,000 cases, there were 323 cases (32.3%) of adenocarcinoma, 5 cases of other malignant tumors, 9 cases of high-grade prostatic intraepithelial neoplasia without a carcinoma, and only 8 cases of atypical small acinar proliferation. Among the 323 cases of adenocarcinoma, there were 38 cases (11.8%) of microcarcinomas <0.1 cm and 101 cases (31.3%) of small adenocarcinomas <0.3 cm in length. In the needle biopsy specimens, 59 cases (18.3%) were classified as clinically insignificant carcinomas. Among them, 37 cases underwent radical prostatectomy, which turned out to be clinically significant carcinomas in 24 cases (64.9%).
CONCLUSIONS
Routinely performed immunohistochemistry combined with the new sample processing method is very effective for detecting microscopic carcinoma foci as well as differentiating carcinoma from benign conditions mimicking cancer.

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