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Kyoung-Mee Kim 10 Articles
Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer
Sujin Park, Junsik Kim, Woncheol Jang, Kyoung-Mee Kim, Kee-Taek Jang
J Pathol Transl Med. 2023;57(2):113-122.   Published online March 14, 2023
DOI: https://doi.org/10.4132/jptm.2023.02.01
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AbstractAbstract PDF
Background
Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression.
Methods
We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually.
Results
The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression.
Conclusions
This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.
A standardized pathology report for gastric cancer: 2nd edition
Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho
J Pathol Transl Med. 2023;57(1):1-27.   Published online January 15, 2023
DOI: https://doi.org/10.4132/jptm.2022.12.23
  • 1,063 View
  • 227 Download
AbstractAbstract PDFSupplementary Material
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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
  • 3,276 View
  • 160 Download
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
Molecular Testing for Gastrointestinal Cancer
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y. Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
J Pathol Transl Med. 2017;51(2):103-121.   Published online February 19, 2017
DOI: https://doi.org/10.4132/jptm.2017.01.24
  • 16,480 View
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  • 46 Citations
AbstractAbstract PDF
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.

Citations

Citations to this article as recorded by  
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    Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
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    Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi,
    Journal of Pathology and Translational Medicine.2023; 57(1): 1.     CrossRef
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    Familial Cancer.2021; 20(2): 145.     CrossRef
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    Faranak Khanipouyani, Hassan Akrami
    Journal of Gastrointestinal Cancer.2021; 52(3): 922.     CrossRef
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PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors
Yooju Shin, Jiyeon Hyeon, Boram Lee, Sang Yun Ha, Min Eui Hong, In Gu Do, Kyoung-Mee Kim
J Pathol Transl Med. 2015;49(1):23-29.   Published online January 15, 2015
DOI: https://doi.org/10.4132/jptm.2014.10.08
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  • 7 Citations
AbstractAbstract PDF
Background
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

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Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples
Soomin Ahn, Jeeyun Lee, Ji-Youn Sung, So Young Kang, Sang Yun Ha, Kee-Taek Jang, Yoon-La Choi, Jung-Sun Kim, Young Lyun Oh, Kyoung-Mee Kim
Korean J Pathol. 2013;47(4):348-354.   Published online August 26, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.348
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  • 9 Citations
AbstractAbstract PDF
Background

Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical.

Methods

BRAF mutations were tested by dual-priming oligonucleotide-polymerase chain reaction (DPO-PCR), direct sequencing and subsequently retested with a real-time PCR assay, cobas 4800 V600 mutation test. In total, 64 tumors including 34 malignant melanomas and 16 papillary thyroid carcinomas were analyzed. DNA was extracted from formalin-fixed paraffin embedded tissue samples and the results of cobas test were directly compared with those of DPO-PCR and direct sequencing.

Results

BRAF mutations were found in 23 of 64 (35.9%) tumors. There was 9.4% discordance among 3 methods. Out of 6 discordant cases, 4 cases were melanomas; 3 cases were BRAF V600E detected only by cobas test, but were not detected by DPO-PCR and direct sequencing. One melanoma patient with BRAF mutation detected only by cobas test has been on vemurafenib treatment for 6 months and showed a dramatic response to vemurafenib. DPO-PCR failed to detect V600K mutation in one case identified by both direct sequencing and cobas test.

Conclusions

In direct comparison of the currently available DPO-PCR, direct sequencing and real-time cobas test for BRAF mutation, real-time PCR assay is the most sensitive method.

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Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters
Mee-Yon Cho, Jin Hee Sohn, So Young Jin, Hyunki Kim, Eun Sun Jung, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Joon Mee Kim, Yun Kyung Kang, Joon Hyuk Choi, Dae Young Kang, Youn Wha Kim, Eun Hee Choi
Korean J Pathol. 2013;47(3):227-237.   Published online June 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.227
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AbstractAbstract PDF
Background

There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients.

Methods

We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report.

Results

Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms.

Conclusions

A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET.

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Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination
Go Eun Bae, Nara Yoon, Ha Young Park, Sang Yun Ha, Junhun Cho, Yunkyung Lee, Kyoung-Mee Kim, Cheol Keun Park
Korean J Pathol. 2013;47(2):163-166.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.163
  • 5,723 View
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  • 7 Citations
AbstractAbstract PDF

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.

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Plexiform Angiomyxoid Myofibroblastic Tumor of the Stomach: Report of Two Cases and Review of the Literature
Youngran Kang, Wonkyung Jung, In-Gu Do, Eui Jin Lee, Min Hyeong Lee, Kyoung-Mee Kim, Jongsang Choi
Korean J Pathol. 2012;46(3):292-296.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.292
  • 7,235 View
  • 53 Download
  • 27 Citations
AbstractAbstract PDF

Plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach is a recently recognized entity. Because of its rarity, only 22 cases have been reported in the English-language literature and most of these are single case reports. We report two cases of gastric PAMT. The tumor cells were bland and plexiform arranged in a myxoid stroma, which was positive for alcian blue. Immunohistochemically, the tumor cells were positive for smooth muscle actin, but negative for c-kit, CD34, desmin, S-100 protein, epithelial membrane antigen, neurofilament, and protein kinase C-theta. Mutation analyses for exon 9, 11, 13, and 17 of KIT genes and 12, 14, and 18 of the platelet-derived growth factor receptor alpha (PDGFRA) genes were performed and the tumors were wild-type for mutation.

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Gastric Adenocarcinoma of Fundic Gland Type: Report of Three Cases
Eun Su Park, Young Eun Kim, Cheol Keun Park, Takashi Yao, Ryoji Kushima, Kyoung-Mee Kim
Korean J Pathol. 2012;46(3):287-291.   Published online June 22, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.287
  • 8,485 View
  • 88 Download
  • 20 Citations
AbstractAbstract PDF

Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.

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JPTM : Journal of Pathology and Translational Medicine