Journal of Pathology and Translational Medicine

Jae Hyuk Lee

21 Articles

Type and Incidence of Soft Tissue Sarcomas in Korea: 2001-2007.: Kyung Un Choi, Hae Youn Kang, Heasoo Koo, Mi Seon Kwon, Dong Hoon Kim, Mi Jung Kim, Su Jin Kim, Young Sill Kim, Chul Hwan Kim, Yong Koo Park, Hye Rim Park, Seung Sam Paik, Jin Young Yoo, Anhi Lee, Jae Hyuk Lee, Hyekyung Lee, Kyu Yun Jang, Young Chae Chu, Joon Hyuk Choi; Korean J Pathol. 2011;45(6):557-563.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.557

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BACKGROUND
The Korean Bone and Soft Tissue Pathology Study Group of the Korean Society of Pathologists conducted a nationwide retrospective analysis of soft tissue sarcoma (STS) to provide the clinicopathologic characteristics of STS within the population of the Republic of Korea.
METHODS
The cases of STS were collected during a 7-year period (2001-2007) from 19 institutes in Korea. All cases were classified according to the histologic criteria proposed by the World Health Organization. Clinicopathologic data were reviewed.
RESULTS
Data from 722 patients (median age, 50 years) were collected. Data showed a slight male predominance. The most frequent types of STS in decreasing order were liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and synovial sarcoma. STS occurred throughout the body, although approximately half (47.8%) were located in the extremities. The majority of STS was histologically classified as high grade with a large tumor size (>5 cm). The overall survival rate for the patients was 76.3% (median follow-up time, 26 months; range, 1 to 89 months). Histologic grade, tumor size, American Joint Committee on Cancer stage, tumor site, and resection status were prognostic. Significant independent adverse prognostic factors were large tumor size (>5 cm) and tumor site other than extremities.
CONCLUSIONS
We reported the distribution and characteristics of STS in the Republic of Korea.

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Distribution and survival of primary sarcoma in Korea: A single center analysis of 2017 cases
Sung Jun Jo, Kyeong Sik Kim, Kyo Won Lee, Jae Berm Park, Yoon-La Choi, Jeong Il Yu, Su Jin Lee, Dong Il Choi, Sung Joo Kim
Korean Journal of Clinical Oncology.2018; 14(1): 30. CrossRef

Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma.: Kyung Hwa Lee, Soong Lee, Hyeon Min Lee, Seung Chul Back, Sung Bum Cho, Jae Hyuk Lee; Korean J Pathol. 2011;45(4):397-405.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.397

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Abstract PDF

BACKGROUND
The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance.
METHODS
Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method.
RESULTS
Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041).
CONCLUSIONS
Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

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A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer
Pierina Cetraro, Julio Plaza-Diaz, Alex MacKenzie, Francisco Abadía-Molina
Cancers.2022; 14(7): 1671. CrossRef

Differences in Expression of VEGF-A, VEGFR-1, VEGFR-2 and Microvessel Density in Colorectal Cancer with Liver Metastasis.: Eun Hui Jeong, Young Kim, Byeong Woo Min, Kyung Hwa Lee, Hyun Soo Kim, Jae Hyuk Lee; Korean J Pathol. 2010;44(6):571-580.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.571

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Abstract PDF: BACKGROUND
Colorectal cancer (CRC) is one of the most common malignant neoplasms and is a leading cause of mortality worldwide. Metastasis to the liver is a frequent event in patients with CRC. An essential step in the metastatic cascade is angiogenesis.
METHODS
This study included 45 patients who underwent a partial colectomy with hepatic resection for CRC with hepatic metastases. Immunohistochemistry was performed using vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1, VEGFR-2, and CD34 antibodies to examine the relationship between CRC with liver metastases and angiogenesis.
RESULTS
CRC showed significantly stronger expression of VEGF-A, VEGFR-1, and VEGFR-2 than liver metastases (p < 0.05). Microvessel density was also higher in CRC than in liver metastases (p < 0.05).
CONCLUSIONS
Compared with previous studies, we found a higher expression of VEGF-A, VEGFR-1, VEGFR-2, and microvessel density in CRC than in liver metastases, which could be ascribed to a difference in vessel distribution and blood supply in each organ. Given its profuse blood supply and distinct cell populations, the liver might provide a rich milieu for tumor cell growth with less expression of angiogenesis-inducing agents.

Prognostic Value of Phosphorylated Akt and Survivin Expression in Gastric Adenocarcinoma.: Soong Lee, Yun Cheol Kim, Hyeon Min Lee, Ki Sang Lee, Byung Chul Shin, Hyung Seok Kim, Jae Hyuk Lee, Chang Soo Park, Kyung Hwa Lee; Korean J Pathol. 2010;44(3):252-258.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.252

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Abstract PDF

BACKGROUND
pAkt (the phosphorylated form of the proto-oncogene protein c-akt) and survivin (human BIRC5 protein) are candidate apoptosis-related molecules that may be responsible for cancer progression. The aim of this study was to determine the expression of pAkt and survivin in malignant stomach neoplasm, and their value as prognostic indicators of cancer.
METHODS
The expression of pAkt and survivin in 144 cases of gastric cancer was detected by immunohistochemistry and compared with established clinicopathological parameters and prognosis of this disease.
RESULTS
Expression of pAkt showed significant correlations with depth of invasion, lymph node and distant metastasis, as well as the stage (p < 0.05 for all three correlations), but not with the Lauren classification. Survivin expression closely correlated with histological type, Lauren classification, depth of invasion, metastasis, and stage (p < 0.05 for all). The overall survival of patients with pAkt/survivin expression was inferior to that of patients with loss of pAkt/survivin expression. Cox multivariate analysis demonstrated a significant correlation between stage (p = 0.04), survivin expression (p = 0.02), and prognosis.
CONCLUSIONS
Patients with pAkt/survivin expression in gastric cancer are at increased risk of cancer-related mortality via the apoptosis resistance pathway. Expression of pAkt and survivin could be used as a prognostic indicator for gastric cancer.

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Transcriptome analysis reveals GPNMB as a potential therapeutic target for gastric cancer
Feifei Ren, Qitai Zhao, Bin Liu, Xiangdong Sun, Youcai Tang, Huang Huang, Lu Mei, Yong Yu, Hui Mo, Haibin Dong, Pengyuan Zheng, Yang Mi
Journal of Cellular Physiology.2020; 235(3): 2738. CrossRef
The Relationship Between Estrogen/Progesterone Receptor and Expression of mTOR/pAkt Proteins and the Analysis of Prognosis in Breast Cancer
Sun Wook Han, Moon Soo Lee, Sung Yong Kim, Gil Ho Kang, Zi Sun Kim, Cheol Wan Lim, Ji Hyun Lee, Hyun Ju Lee, Mee-Hye Oh, Min Hyuk Lee
Journal of Breast Disease.2013; 1(1): 8. CrossRef
Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer
Mee-Hye Oh, Hyun Ju Lee, Seol Bong Yoo, Xianhua Xu, Jae Sung Choi, Yong Hoon Kim, Seok Yeol Lee, Choon-Taek Lee, Sanghoon Jheon, Jin-Haeng Chung
Virchows Archiv.2012; 460(6): 601. CrossRef

Aberrant Promoter Methylation of the Vimentin Gene in Colorectal Cancer Associated with the Adenoma-Carcinoma Sequence.: Mi Hee Cho, Yu Mi Lee, Jin Sook Kim, Hyun Soo Kim, Kyung Hwa Lee, Sang Woo Juhng, Jae Hyuk Lee; Korean J Pathol. 2010;44(2):179-186.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.179

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Abstract PDF

BACKGROUND
DNA hypermethylation is a common epigenetic finding in human cancers and is closely associated with transcriptional silencing. In the present study, we investigated the proportion of colorectal neoplasms that showed the adenoma-carcinoma progression and vimentin gene methylation.
METHODS
Methylation status of the vimentin gene was examined in nontumoral mucosa, adenomas, and adenocarcinomas from 45 colorectal cancer patients who had adenoma and adenocarcinoma together. Methylation status was determined by bisulfite modification and the methylation-specific polymerase chain reaction. The expression of the vimentin gene product was also examined by immunohistochemistry.
RESULTS
Promoter methylation of vimentin was detected in 80% (36 out of 45 cases) of adenocarcinomas, 82.2% (37 of 45) of adenomas, and 28.9% (13 of 45) of normal epithelia, and the difference between neoplastic and normal specimens was statistically significant (p < 0.001). However, no significant correlations were observed between methylation frequency and clinicopathologic variables. Immunohistochemically, vimentin expression was not observed in either normal epithelial cells or tumor cells. Protein expression and vimentin promoter methylation were not associated.
CONCLUSIONS
The frequency of aberrant methylation of the vimentin gene was high in colonic adenomas and adenocarcinomas. This result suggests that the methylation status of vimentin may be clinically beneficial in screening for colorectal cancer patients and may be helpful in clarifying colorectal cancer biology.

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Epigenetic Modifications as Biomarkers of Tumor Development, Therapy Response, and Recurrence across the Cancer Care Continuum
Margaret Thomas, Paola Marcato
Cancers.2018; 10(4): 101. CrossRef
Aberrant promoter methylation of beta‐1,4 galactosyltransferase 1 as potential cancer‐specific biomarker of colorectal tumors
Maria Luana Poeta, Emanuela Massi, Paola Parrella, Pasquale Pellegrini, Mariangela De Robertis, Massimiliano Copetti, Carla Rabitti, Giuseppe Perrone, Andrea Onetti Muda, Francesca Molinari, Elena Zanellato, Stefano Crippa, Damiano Caputo, Marco Caricato,
Genes, Chromosomes and Cancer.2012; 51(12): 1133. CrossRef

Metastatic Osteosarcoma to the Prostate: A Case Report.: Hyoung Yeon Seo, Jae Hyuk Lee, Chang Soo Park, Jin Gyoon Park, Sung Taek Jung; Korean J Pathol. 2009;43(5):475-477.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.475

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Abstract PDF: The most common site for the metastasis of osteosarcoma is the lung, and other sites of metastases include the bone, lymph node, pleura and liver. Although unusual extrapulmonary metastases have been reported with the improvement of the therapeutic results for the primary lesions, they are exceptionally rare. We report here on a case of prostatic metastasis of an osteosarcoma of the proximal tibia, and this developed seven years after successful resection, and four years after resection of a pulmonary metastasis. Radical prostatectomy was performed, and histological examination demonstrated metastatic osteosarcoma. To the best of our knowledge, this is the first case of prostatic metastasis of osteosarcoma in the medical literature.

Expression of Survivin in Gastric Carcinoma and its Relation to Tumor Cell Proliferation and Apoptosis.: Wan Sik Lee, Sung Bum Cho, Jong Sun Rew, Jae Hyuk Lee, Chang Soo Park, Young Eun Joo; Korean J Pathol. 2009;43(4):329-334.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.329

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Abstract PDF

BACKGROUND
Survivin, a novel antiapoptotic gene has been linked with tumor development and progression in various human carcinomas including gastric carcinomas. The aim of this study was to evaluate the expression of survivin in gastric carcinoma and its correlation with tumor cell proliferation and apoptosis. METHODS: Expression of survivin was evaluated immunohistochemically in 84 surgically resected gastric carcinomas. Tumor cell apoptosis was evaluated with terminal deoxynucleotidyl transferase (TdT) mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), and Ki-67 immunostaining was used for evaluation of tumor cell proliferation. RESULTS: Expression of survivin was noted in 53.6% of the gastric carcinomas, and was significantly associated with depth of invasion, status of lymph node metastasis or tumor stage (p=0.022, 0.034, 0.040, respectively). There was an inverse correlation between survivin expression and apoptotic index (p=0.015). But there was no significant correlation between survivin expression and Ki-67 labeling index (p=0.430). CONCLUSIONS: These results suggest that survivin expression may contribute to tumor development and progression by inhibiting apoptosis in human gastric carcinoma.

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Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression
SOO-AH KIM, RAN HONG
Oncology Letters.2014; 7(5): 1589. CrossRef

Solitary Splenic Metastases from Uterine Cervical Cancer: Case Reports and Review of the Literature.: Jo Heon Kim, Yoo Duk Choi, Jae Hyuk Lee, Jong Hee Nam, Sang Woo Juhng, Yang Seok Koh, Chol Kyoon Cho, Chan Choi; Korean J Pathol. 2008;42(5):317-322.

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Abstract PDF: Splenic metastasis from gynecologic tumors is extremely rare, especially in the absence of apparent disease at other sites. We report two patients that underwent splenectomy for a solitary splenic metastasis from uterine cervical carcinoma. In case 1, a 54-year-old woman with FIGO Stage IIb squamous cell carcinoma of the uterine cervix treated with radiotherapy and chemotherapy developed a solitary splenic metastasis 10 months after initial treatment. In case 2, a 46-year-old woman with FIGO Stage IIb adenocarcinoma of the uterine cervix treated with radiotherapy and chemotherapy was found to have a solitary splenic metastasis 11 months after treatment. Thus all abdominal organs including the spleen must be evaluated for metastases during follow-up of gynecologic tumors.

An Immunohistochemical Study of Angiogenesis in Tumor Emboli.: Jo Heon Kim, Chan Choi, Jae Hyuk Lee, Ji Shin Lee, Sung Sun Kim, Chang Woo Han, Sang Woo Juhng; Korean J Pathol. 2007;41(4):252-257.

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Abstract PDF: BACKGROUND
Angiogenesis, which is essential for tumor growth, is known to occur in the extravascular stroma. However, vascular structures were noted in intravascular tumor emboli in surgical specimens. This prompted our investigation of the frequency and morphology of angiogenesis in tumor emboli.
METHODS
Hematoxylin-eosin stained specimens were reviewed for tumor emboli, in 21 cases of stomach adenocarcinoma and 22 cases of colon adenocarcinoma. The cases were examined with immunohistochemistry using antibodies against epithelial antigen (cytokeratin), endothelial antigens (CD31, CD34), lymphatic endothelial antigen (D2-40), and proliferation-associated antigen (MIB1).
RESULTS
Endothelial cells were observed in 16 tumor emboli among four (19.1%) of the 21 cases of stomach adenocarcinoma and in 32 tumor emboli among four (18.2%) of the 22 cases of colon adenocarcinoma. The endothelial cells in the tumor emboli showed papillary ingrowth from the vessel wall, formation of vascular lumens, scattered distribution, or surface coating of the emboli. Some of the endothelial cells in the tumor emboli were D2-40-positive, and some were MIB1- positive.
CONCLUSIONS
These findings demonstrated that angiogenesis occurs in intravascular tumor emboli as well as in the extravascular stroma. Angiogenesis in the tumor emboli may reflect an active process and may facilitate tumor growth.

Expression of VEGF, MMP-9 and Neovascularization in Relationship to the Clinical Behavior of Giant Cell Tumors of Bone.: Kyung Hwa Lee, Jo Heon Kim, Min Keun Shim, Chang Woo Han, Sung Sun Kim, Sang Woo Juhng, Sung Taek Jung, Jae Hyuk Lee; Korean J Pathol. 2006;40(6):420-426.

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Abstract PDF: BACKGROUND
Giant cell tumors (GCT(s)) of bone are benign but can be locally aggressive neoplasms. Their clinical behavior has been difficult to predict on the basis of histology alone. This study investigated the neovascularization and expression of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase-9 (MMP-9) in GCT(s) of bone; in addition we evaluated their relationship to clinical behavior.
METHODS
We evaluated the microvessel number and density in 33 samples of giant cell tumor using CD34 immunohistochemistry. In addition, we examined the immunohistochemical expression of VEGF and MMP-9.
RESULTS
The microvessel number alone, not the microvessel density, had statistical association with the clinical stage of GCT(s) (p=0.045). The proportion of cases with strong expression of VEGF increased with advancing clinical stage, however, these results were not statistically significant (p=0.257). The percentage of the cases with strong expression of MMP-9 also increased with advancing clinical stage and this was statistically significant (p=0.022).
CONCLUSIONS
These results suggest that intratumor microvessel count and the expression of MMP-9 correlate with GCT stage. Evaluation of their expression may therefore provide prognostic information on the aggressive behavior of GCT(s) of bone.

Clonal Analysis of Neurofibroma by PCR Amplification of HUMARA Gene.: Jae Hyuk Lee, Seung Sang Han, Hyun Sik Oh, Yoo Duk Choi, Hyun Joong Kim, Kyung Hwa Lee, Jong Hee Nam, Chan Choi, Sang Woo Juhng; Korean J Pathol. 2003;37(6):421-428.

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Abstract PDF: BACKGROUND
While neurofibromas have generally been regarded as polyclonal hyperplastic lesions, it remains unclear whether the tumor is a true neoplasm or a hyperplastic lesion.
METHODS
Determination of clonality by X chromosome inactivation pattern was investigated in twenty-one cases of neurofibroma employing enzyme digestion and PCR of the HUMARA gene. The histological, immunohistochemical, and ultrastructural characteristics of the tumors were also examined.
RESULTS
Immunohistochemically, most of the tumor cells showed vimentin and S-100 protein positivity. Axons were demonstrated by neurofilament protein positivity and were seen mainly at the periphery and rarely in the central portion of the tumor. Ultrastructurally, the tumors were composed of a variety of cell types: perineurial cells, Schwann cells, fibroblasts, and axons. X chromosome inactivation analysis was completed on thirteen out of fifteen cases in which DNA was successfully extracted. Of thirteen neurofibromas that were heterozygous at the HUMARA loci, eleven showed a polyclonal pattern. The remaining two cases were considered as indeterminate for clonality because of unequal band intensity and failure to obtain the normal control DNA.
CONCLUSION
The results from this study suggest that neurofibromas are polyclonal in origin and might be a neoplastic lesion comprising non-neoplastic cells among constituent components.

Mesoblastic Nephroma of Adulthood.: Jae Woo Park, Jae Hun Chung, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 2001;35(6):551-554.

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Abstract: Mesoblastic nephroma is a benign neoplasm of the kidney, which is usually diagnosed during the first six months of life. Incidence in adults is exceedingly rare. We report herein a case of mesoblastic nephroma that occurred in the upper pole of the right kidney of a 39-year-old woman. It was a round mass measuring 3X3X2 cm in dimension. Microscopically, it consisted of uniform spindle cells with foci of hyalinization and dystrophic calcification. Tubular structures were entrapped in the tumor. Upon immunohistochemical staining, the spindle cells were found to be positive for smooth muscle actin, desmin, and vimentin. The epithelial cells of the entrapped tubules were positive for cytokeratin. On electron microscopic examination, the spindle cells demonstrated smooth muscle differentiation identified by indented nuclei, microfilaments beneath the cell membrane, dense bodies, and basal lamina-like materials.

Clinicopathologic Characteristics of Replication Error-Positive Gastric Adenocarcinoma in Korean.: Jae Hyuk Lee, Mi Hwa Kim, Wan Sik Lee, Young Jin Kim, Mi Sun Jee, Kwang Min Lee, Sang Woo Juhng, Chan Choi; Korean J Pathol. 2000;34(7):488-493.

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Abstract PDF: The purpose of this study is to obtain the clinicopathological characteristics of replication error-positive (RER ) gastric adenocarcinoma in Korean, and to identify the significance of RER in adenoma stage of gastric carcinogenesis. Microsatellite instability was examined at D2S71, D2S119, D3S1067, D6S87, D11S905, DM, AR, VWF, HPRT, and BAT-26 loci. Frameshift mutation of BAX gene was analyzed in RER tumors. Normal and tumor DNA of 76 cases of gastric carcinoma and 25 cases of adenoma were examined. RER was found in 8 of 76 cases (10.5%), and it was more frequently found in adenocarcinoma of female (17.7%) than those of male (4.8%). The frequency of RER was not different between the histologic types, age of the patient, anatomical location of the carcinoma, and the stage. The RER found in adenoma suggests that RER contributes to the malignant transformation early in the adenoma stage of the gastric carcinogenesis. None of the RER tumors revealed frameshift mutation of the BAX gene.

Malignant Granular Cell Tumor of the Shoulder: A case report.: Jae Hun Chung, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Cheol Lee; Korean J Pathol. 2000;34(6):475-479.

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Abstract PDF: A malignant granular cell tumor (MGCT) occurred in the left shoulder of a 62-year-old man. The patient underwent wide marginal excision followed by chemotherapy and radiotherapy. A metastatic tumor was identified in the axillary lymph node 22 months after the excision of the shoulder mass. The primary tumor was a poorly circumscribed mass measuring 5 5 4 cm. On cut section, it was a solid mass with yellowish tan color. Histologically, both primary and metastatic tumor consisted of polygonal cells with abundant granular cytoplasm and a vesicular nucleus with a prominent nucleolus. Two to three mitotic figures per ten high power fields at 200 were counted. Tumor cells were weakly stained with periodic acid-Schiff (PAS) preparation both before and after diastase digestion, and were positive for S-100 protein, neuron-specific enolase (NSE), and vimentin. By electron microscopy, the cytoplasm was filled with numerous autophagolysosomes containing myelin figures, mitochondria, and fragmented rough endoplasmic reticula. Basal laminae and angulated bodies were also noted. These findings suggest schwannian differentiation of this tumor.

Analyses of Genetic Alterations in Breast Cancers by Comparative Genomic Hybridization.: Jin Man Kim, Young Mi Jeon, Young Hyeh Ko, Kyu Sang Song, Howe J Ree, Joo Seob Keum, Jae Hyuk Lee, Sun Hoe Koo; Korean J Pathol. 1999;33(8):603-613.

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Abstract PDF: Transformation and progression of breast cancer are thought to be caused by an accumulation of complex genetic alterations, but little is known about specific changes. In this study, the author has undertaken a genome-wide screening to detect genetic changes in 20 cases of breast cancer among Koreans, including 16 infiltrating ductal carcinomas, 2 medullary carcinomas, 1 invasive lobular carcinoma, and 1 borderline phyllodes tumor. Comparative genomic hybridization (CGH) was used to screen for DNA sequence gains and losses across all human chromosomes. Simultaneous immunohistochemical staining for c-erbB-2 (Her-2/neu), c-myc, cyclin D1, and p53 protein was done to make comparisons with nuclear grade and that with CGH results. Biotin-labeled tumor DNA and digoxigenin-labeled normal DNA were hybridized to normal metaphase cells. The fluorescence signals were captured by fluorescence microscope after detection by avidin-FITC and anti-digoxigenin rhodamine. Then, the ratio of fluorescence was calculated by an image analyzer. The immunohistochemical staining was done in paraffin-embedded tissue with an LSAB kit and avidin-biotin complex (ABC) method. The CGH results showed gains on chromosomes 8q (40%), 1q (30%), 17q (15%), 20q (15%), 18q (15%), 5p (15%), and 13q (15%). Deletions were on chromosomes 17p (45%) and 22q (20%). High-level amplifications (green/red ratio >1.5) were noted on chromosomes 1p31, 1q, 3q25-qter, 5p, 7q31-qter, 8q, 9p22-qter, 10p, 11p, 11q22-qter, 12p, 12q24, 14q21-qter, 15q23-qter, 17q, 18p, 18q12-qter, 20p, and 20q. By comparison with infiltrating ductal carcinoma, the two medullary carcinomas showed high-level amplification on chromosomes 1p31, 1q, 8q, 10p, 11p and 12p. c-erbB-2, c-myc, cyclin D1, and p53 protein expression was immunohistochemically detected in 9 of 20 (45%), 8 of 20 (40%), 10 of 20 (50%), and 13 of 20 (65%), respectively. The results indicate that the amplification on chromosome 8q, 1q and the deletions on chromosomes 17p and 22q are the most frequent genetic alterations in breast cancers among Koreans. The results reveal a different pattern of genetic alteration from previous studies. The CGH results were not correlated with the immunohistochemical profiles. The amplification pattern of medullary carcinomas was quite different from the pattern of infiltrating ductal carcinomas. The CGH was thought to be very useful in the screening of genetic alterations of solid tumors.

Relationship between Insulin Secretory Capacity and Mitochondrial Morphology in Pancreatic beta-Cell.: Seung Won Yang, Jae Hyuk Lee, Chang Soo Park, Min Young Chung; Korean J Pathol. 1999;33(5):326-336.

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Abstract PDF: To investigate the relationship between insulin response and morphometric changes of the mitochondria of pancreatic beta-cell, this study was performed using hyperglycemia and streptozotocin as oxidative stresses. Adult and neonatal rats were used. Intravenous glucose tolerance test (IVGTT) and morphologic examination of pancreas using immunohistochemical stain, in situ end-labeling method and electron microscopic study were performed. Various mitochondrial parameters were measured by image analyzer. Immunohistochemical stain revealed a markedly reduced islet size and decreased number of beta-cells and the increased number of non-beta-cell in adult and neonatoal streptozotocin group, and the appearance of insulin positive cells throughout the exocrine parenchyma in neonatal streptozotocin group. Three days after injection of streptozotocin in adult streptozotocin group, TUNEL stain showed increased apoptotic cells in islets. Ultrastructurally, beta-cells in adult streptozotocin group showed increase in number and size of mitochondria, and disruption of mitochondrial structures. Hyperglycemic group and neonatal streptozotocin group showed preserved mitochondrial ultrastructure. Ultrastructural morphometric study revealed increase in size and number of mitochondria and decrease in mitochondrial contour index in adult streptozotocin-treated rats, which suggested mitochondrial degeneration. Hyperglycemic group showed mild increase in size of mitochondria. Increased number of mitochondria was also observed in neonatal streptozotocin group. IVGTT revealed marked decrease in insulin response in adult streptozotocin group, and non-insulin-dependent diabetes mellitus pattern in glucose and insulin response in neonatal streptozotocin group. Hyperglycemic group showed a glucose and insulin response similar to control group. The above results suggest that a severe oxidative injury may cause degeneration and disruption of mitochondria of pancreatic beta-cell, and may be associated with substantial apoptotic cell death. The changes in the morphology and the number of mitochondria may result from streptozotocin treatment within neonatal period and hyperglycemia treatment, which may be associated with changes in insulin response.

A Comparative Study of Immunohistochemistry and PCR-SSCP for Detection of p53 Mutation In Gastric Carcinoma.: Jong Soon Kim, Jae Hyuk Lee, Min Cheol Lee, Chang Soo Park, Sang Woo Juhung; Korean J Pathol. 1998;32(1):21-28.

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Abstract PDF: Mutation of the p53 tumor-suppressor gene in exons 4 through 9 was examined in 34 cases of primary advanced gastric cancer using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and the results were compared with p53 protein expression as determined by immunohistochemistry (IHC) using a monoclonal antibody(DO-1). p53 protein detected by IHC was observed in 14 cases (41.2%) and genotypic mutation detected by PCR-SSCP in exons 4-9 was observed in 13 cases (38.2%) One case showed an aberrant band on PCR-SSCP both in Exon 7 and Exon 8/9. p53 alteration detected by either IHC or PCR-SSCP was observed in 19 cases (55.9%), but only 8 cases (23.5%) showed both p53 mutation and protein expression. We also tried to obtain the correlation between relative intensity of the shifted bands on PCR-SSCP and percentage of positive cells by IHC, but a significant correlation was not seen between relative intensity of shifted bands on PCR-SSCP and positve cell ratio. A discrepancy between p53 protein expression and p53 mutation is observed in primary gastric carcinomas. The reason for this discrepancy are not apparent. However, examination of gastric carcinomas for mutations in other exons may identify a better correlation with protein overexpression. The results obtained in this study suggest that the negative reaction for p53 immunohistochemistry may not necessarily mean no genetic alteration of the p53 locus.

Detection of Human Papillomavirus in Lesions of Uterine Cervix Immunohistochemistry and in situ Hybridization.: Chang Soo Park, Jong Hee Nam, Jae Hyuk Lee, Jong Soon Kim, Seung Jin Oh; Korean J Pathol. 1997;31(4):289-297.

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Abstract PDF: To evaluate the detection of HPV DNA according to subtype of lesions of uterine cervix and its clinical applicability, in situ hybridization (ISH) and immunohistochemistry for HPV were performed in 189 cases of uterine cervical lesion, including 23 cases of low grade squamous intraepithelial lesion (SIL), 115 cases of high grade SIL and 51 cases of invasive carcinoma. Positive immunostaining, brown precipitate, was mainly noted in the nucleus of koilocytes in the superficial and intermediate layer. Positivity of immunostaining was 21.7% in low grade SIL, 13.0% in high grade SIL and 9.8% in invasive carcinoma. Positive reaction in ISH, red precipitate, was noted in the nucleus of not only koilocytes but also non-koilocytes in the superficial and intermediate layer, and dot precipitate was rarely identified in the nest of squamous cell carcinoma. Based on HPV subtype, 6/11 was 21.7% in low grade SIL, 16/18 was 32.2% and 39.2% in high grade SIL and invasive carcinoma, respectively. With regard to their associated HPV types, low grade SILs were heterogeneous and high grade SILs and invasive carcinomas were related with the high oncogenic risk group only. The correlation of HPV subtypes with panHPV was 91.3% in low grade SIL, 91.3% in high grade SIL and 98.0% in invasive carcinoma. These results suggest that detection of HPV infection by ISH may be a more useful method than immunohistochemistry and application of the HPV subtype probe with the panHPV probe could improve the sensitivity of ISH.

Immunohistochemical and Ultrastructural Studies of Gastric Smooth Muscle Tumor.: Hyang Mi Ko, Kyung Soo Kim, Jae Hyuk Lee, Woo Sik Juhng, Sang Woo Juhng; Korean J Pathol. 1996;30(3):245-254.

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Abstract PDF: To evaluate the differentiation status of smooth muscle in gastric stromal tumors which were negative for S-100 protein, immunohistochemistry using desmin, actin, myosin and vimentin was performed in 14 cases of gastric smooth muscle tumors. Ultrastructural Examination was also performed. For comparison a case of leiomyoma of the esophagus, a case of the sigmoid colon, 10 cases of the uterus were also examined. The results obtained were as follows. All gastric smooth muscle tumors showed vimentin-positivity. Six of 14 gastric smooth muscle tumors, (5 of 8 leiomyoma and 1 of 4 leiomyosarcoma) showed positivity for desmin, actin, and myosin(42.9%). All esophageal, colonic, and uterine leiomyomas showed diffuse positive reaction for desmin, actin, and myosin. Vimentin positivity was also noted in leiomyoma of the colon and uterus. Ultrastructurally, a few cells in the gastric stromal tumors had scattered microfilaments with dense bodies, subplasmalemmal dense plaques, and micropinocytic vesicles. However, most of the tumor cells did not have any of the ultrastructural features of smooth muscle differentiation. Leiomyomas of the esophagus and uterus showed many cytoplasmic microfilaments with dense bodies. These results suggest that most of the benign and malignant tumor cells of gastric stromal tumors have features of the undifferentiated cells, immunohistochemically as well as ultrastructurally, although a few cells have. It is speculated that most gastric stromal tumors may have lost their smooth muscle differentiation.

A study of Digital Image Analysis of Chromatin Texture for Discrimination of Thyroid Neoplastic Cells.: Sang Woo Juhng, Jae Hyuk Lee, Eun Kyung Bum, Chang Won Kim; Korean J Cytopathol. 1996;7(1):23-30.

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Abstract PDF: Chromatin texture, which partly reflects nuclear organization, is evolving as an important parameter indicating cell activation or transformation. In this study, chromatin pattern was evaluated by image analysis of the electron micrographs of follicular and papillary carcinoma cells of the thyroid gland and tested for discrimination of the two neoplasms. Digital grey images were converted from the electron micrographs; nuclear images, excluding nucleolus and intranuclear cytoplasmic inclusions, were obtained by segmentation; grey levels were standardized; and grey level histograms were generated. The histograms in follicular carcinoma showed Gaussian or near-Gaussian distribution and had a single peak, whereas those in papillary carcinoma had two peaks(bimodal), one at the black zone and the other at the white zone. In papillary carcinoma. the peak in the black zone represented an increased amount of heterochromatin particles and that at the white zone represented decreased electron density of euchromatin or nuclear matrix. These results indicate that the nuclei of follicular and papillary carcinoma cells differ intheir chromatin pattern and the difference may be due to decondensed chromatin and/or matrix substances.

The Study of Proliferating Cell Nuclear Antigen (PCNA) Reactivity in Fibrohistiocytic Tumors.: Jae Hyuk Lee, Yong Han Park, Hyang Mi Ko, Ji Shin Lee, Chang Soo Park; Korean J Pathol. 1994;28(4):350-357.

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Abstract PDF: Fibrohistiocytic tumors are a diverse group of benign and malignant soft tissue lesions, including dermatofibroma, dermatofibrosarcomaprotuberans, and malignant fibrous histiocytoma. On the clinical point of view, the distinction between benign and malignant lesions and malignancy grading is far more important. Therefore, we investigated 23 fibrohistiocytic tumors, using PCNA (PC10) which was a useful marker of proliferating activity, to differentiate the benign lesions from the malignant and correlate with other prognostic factors including tumor necrosis. cellularity, histologic grade, and mitotic counts. The results obtained were as follows 1) Positive tumor cells were clearly identified by the characteristic diffuse or granular nuclear staining. 2) The number of PCNA-positive tumor cells were 2.16+/-2.39% in dermatofibroma, 16.12+/-7.38% in dermatofibrosacoma protuberans, and 28.02+/-17.47% in the malignant fibrous histiocytoma. The numbers of PCNA-positive tumor cells in the malignant lesions higher than in the benign (p<0.001). 3) Deep seated, large size (>5 cm) and recurred or metastatic cases of MFH were more the high PCNA index (more than 20%) than the low index (less than 20%) groups. 4) PCNA index in MFHs had positive correlation with the number of mitotic counts (r=0.7582, p<0.001), cellularity (r=0.5908, p<0.05) and histologic grade (r=0.4164, p<0.05). These results suggested that reactivity on PCNA might assist in the distinction between benign and malignant lesions in fibrohistiocytic tumors, and could be a useful prognostic factor in the patients with malignant fibrous histiocytoma.

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