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고지원,박하영,배정모,강준,조의주,이승은,강혜윤,홍민의,원재경,최윤라,김완섭,이아원,The Molecular Pathology Study Group of the Korean Society of Pathologists 대한병리학회 2023 Journal of Pathology and Translational Medicine Vol.57 No.5
Background: The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education. Methods: The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education. Results: The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated. Conclusions: Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.
Standardized Pathology Report for Colorectal Cancer, 2nd Edition
김백희,김준미,강경훈,장희진,강동욱,김정호,배정모,서안나,박호성,강윤경,이경화,조미연,도인구,이혜승,장희경,박도윤,강효정,손진희,장미수,정은선,진소영,유은실,한혜승,김윤화,The Gastrointestinal Pathology Study Group of the Korean Society of Pa 대한병리학회 2020 Journal of Pathology and Translational Medicine Vol.54 No.1
The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.
Investigation and Standardization on Current Practice of Renal Transplant Pathology in Korea
조의주,서광선,기정혜,최영진,Renal Pathology Study Group of Korean Society of Pathologists 대한이식학회 2017 Korean Journal of Transplantation Vol.31 No.4
We need to establish an informative guideline to increase inter-institutional and inter-observer reproducibility of renal transplant diagnosis, and to improve the diagnostic ability of pathologists in Korea. A first nation-wide survey for renal transplant pathology was conducted by Renal Pathology Study Group of the Korean Society of Pathologists in 2016, to provide the continued excellence in the transplantation pathology laboratory, and to improve the diagnostic ability for the best treatment of transplant patients. This survey revealed the significant variations in scale, work load and biopsy indications for the renal transplant pathology in various institutions in Korea. The Banff classification were used by all institutions for the diagnosis of renal transplant pathology, but different formats were used: most institutions (70%) used the “2013 Banff classification” while the others were using “2007 Banff classification” (20%) or even older formats. In daily diagnostic practice of the renal allografts, difficulties that pathologists encounter were quite diverse due to different environments they work in. Most respondents agreed that standardized diagnostic practice guidelines, regular education on renal transplant pathology and convenient ways of consultation are further needed. We are currently working toward the enhancement of the expertise of renal pathologists and to increase inter-institutional and inter-observer reproducibility by 1) development of a set of virtual slides of renal allograft biopsies for the training, 2) validation and gathering expert's consensus on the core variables of rejection diagnosis by using virtual slides, and 3) continued education by the developed virtual slide atlas.
장선희,심효섭,김태정,최윤라,김완섭,신동훈,김루시아,박혜성,이건국,이창훈,Korean Cardiopulmonary Pathology Study Group 대한병리학회 2021 Journal of Pathology and Translational Medicine Vol.55 No.3
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.
Metabolic, Metallic and Mitotic Sources of Oxidative Stress in Alzheimer Disease
Smith, Mark A.,Zhu, Xiongwei,Nunomura, Akihiko,Raina, Arun K.,Rottkamp, Catherine A.,Takeda , Atsushi,Perry, George 한림대학교 환경·생명과학연구소 2000 [일송 국제심포지엄] 노화와 만성퇴행성 신경질환 Vol.- No.3
Alzheimer disease (AD) is marked by increases in oxidative damage to macromolecules such as sugars, lipids, proteins and nucleic acids. Notably, such damage is not limited to the lesions of the disease but instead involves all vulnerable neurons. These findings of oxidative abnormalities clearly predate gross described neuronal cytopathology and support the primacy of oxidative damage as an early and dynamic change of AD. Here, we review possible sources of oxidative damage as it applies to AD. Contrary to in vitro findings, correlations between cases with various extents of amyloid-β deposits or neurofibrillary tangles (NFT) show that oxidative damage is in fact reduced with increasing senile plaque and neurofibrillary tangle density (Nunomura et al., 1999a). for amyloid-β, there is a direct negative linear correlation with oxidative damage (Nunomura et al., 1999b). These findings indicate that the formation of the amyloid-β plaques and NFT, long thought of as a deleterious process leading to neuronal death, may in fact be a cytoprotective response (Morsch et al.,1999) to reduce oxidative damage.
신동훈,심효섭,김태정,박혜성,최윤라,김완섭,김루시아,장선희,송준선,김효진,한정호,이창훈,이건국,장세진,Korean Cardiopulmonary Pathology Study Group 대한병리학회 2019 Journal of Pathology and Translational Medicine Vol.53 No.3
Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
장선희,박형규,최윤라,장세진,Cardiopulmonary Pathology Study Group of the Korean Society of Patholo 대한병리학회 2019 Journal of Pathology and Translational Medicine Vol.53 No.6
Background: Assessment of programmed cell death-ligand 1 (PD-L1) immunohistochemical staining is used for treatment decisions in non-small cell lung cancer (NSCLC) regarding use of PD-L1/programmed cell death protein 1 (PD-1) immunotherapy. The reliability of the PD-L1 22C3 pharmDx assay is critical in guiding clinical practice. The Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists investigated the interobserver reproducibility of PD-L1 staining with 22C3 pharmDx in NSCLC samples. Methods: Twenty-seven pathologists individually assessed the tumor proportion score (TPS) for 107 NSCLC samples. Each case was divided into three levels based on TPS: < 1%, 1%–49%, and ≥ 50%. Results: The intraclass correlation coefficient for TPS was 0.902 ± 0.058. Weighted κ coefficient for 3-step assessment was 0.748 ± 0.093. The κ coefficients for 1% and 50% cut-offs were 0.633 and 0.834, respectively. There was a significant association between interobserver reproducibility and experience (formal PD-L1 training, more experience for PD-L1 assessment, and longer practice duration on surgical pathology), histologic subtype, and specimen type. Conclusions: Our results indicate that PD-L1 immunohistochemical staining provides a reproducible basis for decisions on anti–PD-1 therapy in NSCLC.
Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms
강동욱,김백희,김준미,김지훈,장희진,장미수,손진희,조미연,진소영,장희경,한혜승,김정연,김희성,박도연,박하영,이소정,이원애,이혜승,강유나,최영희,The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists 대한병리학회 2021 Journal of Pathology and Translational Medicine Vol.55 No.4
Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.
Song,Hyung Geun,Sung,Rohyun,Park,Seong Hoe,Lee,Geon Kook 충북대학교 의과대학 충북대학교 의학연구소 1996 忠北醫大學術誌 Vol.6 No.1
세포간의 상호작용은 림프구 등의 면역세포들이 완벽한 면역기능을 수행하기 위해 필수적이며, 림프구의, 특히 흉선세포의 분화 및 교육과정에 대단히 중요하다. 동질성 세포유착은 생리적인 상태에서의 세포간의 상호작용을 체외에서 재현하는 모델로 생각되며, 이 같은 현상이 제대로 일어나기 위해서는 일반적으로 에너지 대사가 필요하고 기능적으로 온전한 세포골격(cytoskeleton)이 요구된다. 최근에 인체 백혈구동통항원인 AP4항원은 대부분의 백혈구 및 인체 백혈병세포주들에 비교적 널리 표현되며, 그 세포질내 부분이 protein tyrosine phosphatase의 활성을 가지고 있어 림프구에서의 활성화 초기 신호전달에 관여한다고 알려져 있다. 하지만 백혈구공통항원의 기능에 대해서는 아직 많은 부분이 알려져 있지 않다. 저자들은 항-AP4 항체에 의해 인체 백혈병세포주 Molt-4의 동질성 유착이 유발되었으며, 이 같은 동질성 유착은 에너지 대사와 기능적으로 온전한 세포골격 및 온도, 그리고 Mg²+ 이온의 존재가 요구됨을 알 수 있었다. 그리고 okadaic acid와 같은 인산분해효소 억제제에 의해 흉선세포간의 동질성 세포유착이 저해되었다. 또한 림프구 등의 세포간 유착에 기여한다고 이미 알려져 있는 LFA-1-α 및 -β에 대한 항체들에 의해서는 동질성 유착이 방해받지 않았다. 상기 결과들을 토대로 AP4 항원은, 적절한 리간드의 교합 (engagement)에 의해 인체 백혈병세포주 Molt-4의 동질성 세포유착을 유발하는, 세포표면 수용체의 기능을 가지는 물질임을 확인하였다. 또한 종양세포에서 확인된 이상의 결과는 정상 림프구 혹은 흉선세포에서의 백혈구공통항원의 역할 및 기능을 제시하는 것이라고 할 수 있다. Cell-cell interaction is essential for an immune response of immunocytes to various antigens and for the differentiation and maturation of lymphocytes. Homotypic cell aggregation in the test tube is thought to reflect the important physiologic cell-cell adhesion events; it requires energy, a functionally intact cytoskeleton, and a number of cell adhesion molecules, and can be triggered nonspecifically by phorbol esters. We produced a mAb against leukocyte common antigen (LCA), AP4, which is a cell surface glycoprotein and its molecular weight is 180 to 220 kDa. We now show here that anti-AP4 mAb induce homotypic aggregation of human T-lymphocytic leukemic cell line, Molt-4, which is temperature-, energy-, Mg²+- and Ca²+-dependent, and requires an intact cytoskeleton. hese adhesion properties are rather characteristic of integrins. Nevertheless, mAbs against LFA-1α and -β, which are known to be involved in aggregation of human lumphocytes induced by mAbs against human LCA, are unable to block Molt-4 aggregation. Therefore, the homotypic adhesion pathway triggered by AP4 engagement is most likely to be LFA-1-independent. In addition, inhibition by okadaic acid suggested the requirement of functionally intact protein phosphatases in AP4-induced homotypic aggregation of leukemic cell lines.
Interobserver Variability of Ki-67 Measurement in Breast Cancer
정율리,장민혜,박소연,공경엽,정우희,이지신,The Korean Breast Pathology Ki-67 Study Group 대한병리학회 2016 Journal of Pathology and Translational Medicine Vol.50 No.2
Background: As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. Methods: Thirty observers from thirty different institutions reviewed Ki-67–stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. Results: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. Conclusions: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.