Journal of Pathology and Translational Medicine

Dae Shick Kim

8 Articles

Prognostic Significance of Methylation Profiles in Urothelial Carcinomas of the Bladder.: Hee Jung Park, Eui Jin Lee, Sang Yun Ha, Ghee Young Kwon, Young Lyun Oh, Kyoung Mee Kim, Dae Shick Kim, Seongil Seo, Hyun Moo Lee, Han Yong Choi; Korean J Pathol. 2010;44(6):623-630.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.623

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BACKGROUND
Study on epigenetics of urothelial carcinomas has expanded and allowed better understanding of their correlation with clinicopathologic features. The aim of this study was to determine reliable predictive epigenetic markers for patients with urothelial carcinoma of urinary bladder.
METHODS
In 64 urothelial carcinomas of the urinary bladder, methylationspecific polymerase chain reaction with RAS association domain family 1A (RASSF1A), adenomatous polyposis coli (APC), death-associated protein-kinase (DAPK), runt-related transcription factor 3 (RUNX3), p14, p16 and MGMT was performed and correlated the results with p53 mutations, DNA ploidy, clinicopathologic parameters and recurrences.
RESULTS
Hypermethyation of RASSF1A, APC, DAPK, RUNX3, p14, p16 and MGMT promoters was observed in 35 (54.7%), 29 (45.3%), 18 (28.1%), 18 (28.1%), 9 (14.1%), 2 (3.1%), and 6 (9.4%) cases, respectively. Hypermethylation of RUNX3 and APC was significantly associated with high histologic grades and aneuploidy. Methylation of DAPK was significantly associated with muscle invasion. Methylation of DAPK and RUNX3 genes was significantly associated with recurrence. In survival analyses, methylation of RUNX3 gene and methylation-high (methylation at two or more loci) phenotype was significantly associated with poor recurrence-free survival.
CONCLUSIONS
Methylation of RUNX3 gene and methylation-high phenotype are significant indicator of recurrence.

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DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis
Lihe Dai, Chong Ma, Zhensheng Zhang, Shuxiong Zeng, Anwei Liu, Shijie Tang, Qian Ren, Yinghao Sun, Chuanliang Xu, Shengtao Zhou
PLOS ONE.2016; 11(12): e0167228. CrossRef

Evaluation of Self-collected Pad Sampling for the Detection of HPV In Cervicovaginal Secretion.: Seong Rim Kim, Sang Yong Song, Dae Shick Kim, Jung Won Lee, Chang Soo Park, Duk Soo Bae, Hyen Ji Lee, Kyung Tae Kim, Oh Joong Kwon, Eun Seop Song, Hee Jae Joo, Gheungwhan Ahn; Korean J Pathol. 2004;38(4):258-264.

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Abstract PDF: BACKGROUND
Self-collection of secretion samples for HPV testing is a feasible alternative method for women who would decline to participate in population based cervical cancer programs. The purpose of this study was to determine the sensitivity and specificity of self-sampling for HPV in determining high grade squamous intraepithelial lesion (HSIL) using the pad, and we also wished to compare the results from samples collected by women themselves and those results from samples collected by physicians.
METHODS
Fifty patients voluntarily participated in the sensitivity and specificity study at the university hospitals and 290 volunteers participated in the agreement study at local clinics. DNA was extracted and amplified using HPV L1 consensus primers for the direct sequencing of the pad samples.
RESULTS
For the detection of HSIL, self-collected pad sampling showed good sensitivity (75.0%) and excellent specificity (100%). Two hundreds eighty-six samples from the pads and concurrent physicians?samples showed the agreement at 98.6% with the Kappa, 0.9622 (p=0.0000).
CONCLUSIONS
A self-sampling method using the pad for the detection of HPV DNA is suggested to be an efficient method to access many women for screening easily, rapidly and conveniently. Testing the pad method? utility for a country- or large area-based mass screening study will be necessary in the future.

Immunoexpressions of Thyroid Transcription Factor-1 and bcl-2 in Congenital Cystic Adenomatoid Malformation.: Na Rae Kim, Dong Hoon Kim, Gou Young Kim, Dae Shick Kim, Joungho Han; Korean J Pathol. 2003;37(1):10-14.

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Abstract PDF: BACKGROUND
Congenital cystic adenomatoid malformation (CCAM) is a congenital abnormality of branching morphogenesis of the lung. Thyroid transcription factor-1 (TTF-1) is detected in human respiratory epithelial cells from 11 weeks of gestation, and at full term, TTF-1 expression is confined within type II epithelial cells and in some respiratory nonciliated bronchiolar epithelial cells. Immunoexpression of bcl-2 is intimately related to apoptosis during the development.
METHODS
To elucidate the nature of the lesion, TTF-1 expression was evaluated in twenty-four cases of CCAM (eight cases of type 1 and sixteen cases of type 2) along with immunostaining for bcl-2. For the control group, four cases of fetal lungs (19 week-, 21 week-, 27 week- and 40 week-gestational age) were also evaluated. In all cases of CCAM, TTF-1 was detected in the nuclei of epithelial cells lining the cysts.
RESULTS
TTF-1 was expressed in the majority of the bronchiolar-like epithelial cells of the cysts in CCAM types 1, and 2, where almost 100% of the lining cells of the cysts were TTF-1 positive with variable intensity, while negative TTF-1 expressions were found in the alveolar-like epithelium of the adjacent alveoli or distal nonciliated bronchi. For bcl-2 immunostaining, no lining epithelial cells of the cysts were stained except for the infiltrating lymphocytes. In the control group, strong immunoreactivities found in early fetal stages were absent in the full-term aged lung (40 gestational weeks).
CONCLUSION
These results support the hypothesis that CCAM types 1 and 2 reflect the abnormalities in lung morphogenesis and differentiation that are distinct from those for normally developed alveolar epithelium or adjacent bronchial epithelium, thus retaining the abnormal TTF-1 immunoreactions. Though restricted to CCAM types 1 and 2 in this study, CCAM might be related to TTF-1 rather than apoptosis in the morphogenesis of the developing lung.

Diagnostic Utility of Polymerase Chain Reaction-Based Clonality Analysis for Immunoglobulin Heavy Chain Gene and T-cell Receptor Gamma Chain Gene Rearrangement in Lymphoid Neoplasms.: Eun Yoon Cho, Young Hyeh Ko, Dae Shick Kim, Jae Joon Han, Howe J Ree; Korean J Pathol. 2001;35(6):461-469.

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Abstract: BACKGROUND
The clonality of lymphoid infiltrates determined by polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) or T cell receptor (TCR) genes is not only useful in confirming the diagnosis of malignant lymphoma but also in establishing the lineage of a clonal lymphoid proliferation. We analyzed the efficiency of PCR analyses for IgH and TCRgenes that have been routinely applied for the diagnosis of malignant lymphoma in our laboratory.
METHODS
Paraffin sections of 200 cases were analyzed by seminested PCR. Primers were FRIIIA-LJH/VLJH consensus primer for IgH gene and V-J consensus primer for TCR gene. The cases showing negative results by PCR for TCR gene were further analyzed by multiplex V family primers with heteroduplex analysis.
RESULTS
PCR approach for IgH gene allowed detection of clonality in 100% of cases with false positive rate of 0.3% and false negative rate of 0%. The combination of PCR for TCR consensus primers with multiplex V family primers allowed detection of clonality in 91% of cases with false positive rate of 0.6% and false negative rate of 10.3%.
CONCLUSIONS
Combined analysis of IgH and TCR gene rearragnements by the PCR technique followed by heteroduplex analysis can be a useful diagnostic adjunct to determine the clonality of various lymphoproliferative diseases with high sensitivity. But clinical, morphological and immunophenotypical correlation should be considered to reach the final diagnosis due to a few false positive cases.

Morphohistometric Investigation and bcl-2 Expression in the Placenta of Chromosomally Abnormal Pregnancy.: Joung ho Han, Kyu Rae Kim, Yeon Lim Suh, Mi Kyung Kim, Young Hyeh Ko, Dae Shick Kim, Howe Jung Ree; Korean J Pathol. 1999;33(5):353-360.

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Abstract PDF: To evaluate the significance of placental histology, a collaborative histological and cytogenetic study was performed on the products of 88 spontaneous abortions, and subsequently bcl-2 immunostaining was performed on 62 cases. The morphometric parameters included were DCIRCLE, FORMSHAPE, CPRATIO, and the expression of bcl-2 immunostainig was graded in four categories (I to IV). The results were as follows: 1) 40% (n=35) were chromosomally abnormal: trisomies predominated (57%, n=20) and was followed by triploidy (14%, n=5), double trisomy (6%, n=2), monosomy X (6%, n=2), inversion (9) (6%, n=2). 2) mean of DCIRCLE in chromosomally abnormal pregnancy was 40 micrometer larger than that in chromosomally normal pregnancy (p=0.012, one side t-test), while no difference was found in FORMSHAPE and CPRATIO between chromosomally abnormal and normal pregnancy. 3) bcl-2 expression was found in syncytiotrophoblast and cytotrophoblast. bcl-2 expression was weaker in chromosomally abnormal pregnancy with intensity I and II of 59% than chromosomally normal pregnancy with intensity I and II of 24%. 4) In comparison bcl-2 expression with DCIRCLE, in chromosomally normal abortion one (10%) in I & II and one (3%) in III & IV showed large DCIRCLE (above 360 micrometer), while 11 (85%) in I & II and 3 (33%) in III & IV in chromosomally abnormal pregnancy. It would mean that bcl-2 protein is necessary in preservation of pregnancy and placental morphology. Abnormal villous diameter and weak bcl-2 expression may be suggestive of chromosomal anomaly. Besides other histologic parameters, application of bcl-2 immunostaining and morphometric analysis probably give more sensitive and specific results in identifying chromosomally abnormal abortion.

Significance of the Expression of Cyclin-Dependent Kinase Inhibitor, p27Kip1, in Human Breast Cancer.: Sang Yong Song, Duck Hwan Kim, Yeon Lim Suh, Young Hyeh Ko, Dae Shick Kim, Seok Jin Nam, Jung Hyun Yang; Korean J Pathol. 1998;32(12):1081-1088.

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Abstract: p27Kip1 protein, a negative cell cycle regulator in G1 progression, has been reported to be related with human cancers including colon, breast and non-small cell lung carcinomas. To elucidate a possible prognostic indicator, we studied 49 cases of human breast carcinoma for expression of p27Kip1 protein using an immunohistochemical method, and compared these results with known prognostic parameters of the breast cancer. p27Kip1 protein was intensely stained in nuclei of carcinoma cells in 26 cases (53.1%). The expression rate of p27Kip1 protein was significantly higher in higher nuclear grade (p<0.05), lower histologic grade (p<0.01), lower N classification (p<0.001) and lower clinical stage (p<0.05) than in lower nuclear grade, higher histologic grade, higher N classification and higher clinical stage, respectively. p27Kip1 protein expression was significantly correlated with progesterone receptor status (p<0.05) or cyclin D expression (p<0.05). No statistical correlations were found between expression of p27Kip1 protein and other parameters including tumor size, estrogen receptor status, p53 overexpression and c-erbB-2 expression. The results suggest that reduced expression of p27Kip1 protein plays a role in biologically aggressive behavior of breast carcinoma and might contribute in predicting breast cancer patient's survival.

Cyclin D1 Expression in 101 Cases of Breast Carcinoma.: Duck Hwan Kim, Eun Sook Nam, Hyung Sik Shin, Jin Woo Ryu, Jai Hyang Go, Young Lyun Oh, Sang Yong Song, Dae Shick Kim, Min Chul Lee; Korean J Pathol. 1998;32(4):266-272.

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Abstract PDF: Cyclin D1, a cell cycle regulator essential for G1 phase progression, is a candidate proto-oncogene implicated in pathogenesis of several human carcinomas including breast carcinoma. We studied the cyclin D1 expression in 101 cases of primary breast carcinoma tissues. The overexpression of cyclin D1 was immunohistochemically demonstrated in 34 (37.8%) of 90 cases of invasive breast carcinoma. Positive cyclin D1 staining was seen in 32 of 79 invasive ductal carcinomas, and 2 of 3 mucinous carcinomas. All 5 medullary carcinomas, 2 invasive lobular carcinomas, and 1 metaplastic carcinoma were negative. Cyclin D1 overexpression was observed in 9 of 11 ductal carcinoma in situ (DCIS). Normal epithelial components, either ductal or lobular, were not immunoreactive for cyclin D1. No significant correlations were observed between cyclin D1 immunoreactivity and other parameters including tumor size, clinical stage, nuclear or histologic grades, lymphatic or angioinvasion, lymph node metastasis, and immunohistochemical status of progesterone receptor, p53 and c-erbB-2. The overexpression of cyclin D1 was positively correlated with estrogen receptor status (p=0.025). Based on our results, the cyclin D1 protein aberration may play a role in tumorigenesis of breast carcinoma, but does not seem to have prognostic value in invasive breast carcinoma without hormonal treatment.

Primitive Neuroectodermal Tumor of the Kidney: A case report .: Sang Yong Song, Eun Youn Cho, Jung Won Lee, Jai Hyang Go, Mi Kyung Kim, Dae Shick Kim, Young Hyeh Ko; Korean J Pathol. 1998;32(3):231-236.

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Abstract PDF: Peripheral primitive neuroectodermal tumor (pPNET), a rare, highly aggressive neoplasm of indetermined histogenesis, occurs typically in the soft tissues of the chest wall and the paraspinal region. Comprehensive diagnostic studies including histological, ultrastructural, immunohistochemical and molecular analyses have been stressed to diagnose this entity. We report a case of primary renal PNET which was incidentally found in a 59-year-old man who presented with generalized weakness for 4 months. He was diagnosed as a non-insulin dependent diabetes mellitus 15 years ago and has been made well by oral therapy. An ill-defined mass, measuring 3.5 3 cm, located in the left kidney and perirenal fat, was incidentally found by ultrasonogram during a renal diabetic examination. The mass was resected because of the unresponsiveness against one-year chemotherapy and radiation therapy. Grossly, a homogeneously solid, gray-white mass, measuring 2.8 1.8 cm, was noted in the mid portion of renal cortex. The mass showed severe adhesion to the perirenal fatty tissue. Microscopically, tumor cells were rather uniform, small round with scanty cytoplasm and often showed rosette formation. Ultrastructurally, they showed membrane-bound dense core granules, measuring 125~150 nm, intercellular junctions and microvillous cytoplasmic projections. The tumor cells were uniformly immunoreactive for neuron-specific enolase and were focally immunoreactive for CD99 (013), chromogranin, synaptophysin and cytokeratin. They were not reactive for S-100 protein, vimentin, Leu-7, leukocyte common antigen, desmin and smooth muscle actin. To our knowledge, this is the smallest renal PNET in literature.

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