Journal of Pathology and Translational Medicine

Hoguen Kim

13 Articles

Validation of Gene Expression Changes of Osteopontin and MMP-1 in Primary and Metastatic Colorectal Carcinomas.: Junjeong Choi, Sangkyum Kim, Jeon Han Park, Nam Kyu Kim, Hoguen Kim; Korean J Pathol. 2010;44(3):225-233.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.225

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Abstract PDF: BACKGROUND
Metastasis is one of the most important characteristics of cancer in terms of its impact on patient survival. Unfortunately, identification of altered genes during tumor metastasis is limited.
METHODS
Using high-throughput microarrays containing 19K spotted human oligonucleotides, gene expression of primary and matched metastatic colon cancer were compared in previous study. Although DNA microarray analysis did not demonstrate complete classification of primary and metastatic carcinoma, 80 differentially expressed genes were identified. Among these, expression of osteopontin, matrix metalloproteinase-1 (MMP-1) and serpin A1 was assessed using immunohistochemistry in a validation set containing 43 pairs from tissue microarrays.
RESULTS
The expression of osteopontin was significantly higher in metastatic carcinoma than in primary carcinoma, as indicated by mRNA expression. The expression of MMP-1 was significantly lower in metastatic carcinoma. Expression of serpin A1 was not correlated with the microarray results.
CONCLUSIONS
Osteopontin and MMP-1 expression successfully classified primary and metastatic colorectal carcinomas and further studies on their clinical application is encouraged.

Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability.: Sang Kyum Kim, Junjeong Choi, Hyun Ki Kim, Young Nyun Park, Si Young Song, Hoguen Kim; Korean J Pathol. 2009;43(5):428-434.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.428

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BACKGROUND
High microsatellite instability (MSI-H) colorectal carcinomas (CRCs) with numerous mutations in the microsatellite sequence are characterized by a right-sided preponderance, frequent peritumoral and intratumoral lymphocytic infiltration, and frequent mucin production. However, no study has correlated anatomic site and type of genetic changes with clinicopathologic changes.
METHODS
We analyzed the histopathologic features of 135 MSI-H CRCs and compared them to 140 microsatellite stable (MSS) CRCs. Histopathologic changes in MSI-H were further analyzed according to anatomic sites and genetic changes.
RESULTS
MSI-H CRCs showed previously reported clinicopathologic findings; a right-sided preponderance, an increased number of mucinous carcinomas, and peritumoral lymphoid reactions (p<0.001 for each variable). Increased serum CEA levels showed an MSS CRC preponderance (p=0.013). We further analyzed the histologic differences between right- and left-sided MSI-H tumors. We found that MSI-H CRCs on both sides had similar clinicopathologic findings, except for higher tumor stage (p=0.048) and less frequent abnormal CEA levels in left-sided MSI-H tumors (p=0.027). We found that not all clinicopathologic features were different between hereditary nonpolyposis colorectal cancers (HNPCCs) and sporadic MSI-H CRCs.
CONCLUSIONS
These findings indicate that MSI-H CRCs of the left colon have similar clinicopathologic characteristics as right-sided MSI-H CRCs. We did not find any significant clinicopathological difference between HNPCCs and sporadic MSI-H CRCs.

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Fibroblast Growth Factor Receptor 1 Gene Copy Number and mRNA Expression in Primary Colorectal Cancer and Its Clinicopathologic Correlation
Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Duck-Woo Kim, Sung-Bum Kang, Woo Ho Kim, Hye Seung Lee
Pathobiology.2015; 82(2): 76. CrossRef

Progressive Suppression of Selenium Binding Protein 1 in Gastric Adenoma and Adenocarcinoma.: Hyunki Kim, Hyun Ju Kang, Jong Pil Park, Ju Yeon Pyo, Hoguen Kim; Korean J Pathol. 2008;42(6):344-350.

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Abstract PDF: BACKGROUND
Human selenium binding protein 1 (SELENBP1) is a protein that binds selenium as a cofactor. The decreased expression of SELENBP1 in several types of carcinomas and its association with a poor prognosis have previously been reported on. In this study, we evaluated the expression of SELENBP1 in low-grade and high-grade epithelial dysplasia/ adenomas and adenocarcinomas. METHODS: We analyzed 45 cases of low-grade epithelial dysplasia/adenomas, 42 cases of high-grade epithelial dysplasia/adenomas and 64 cases of adenocarcinomas and all of them were obtained from endoscopic mucosal resection or endoscopic submucosal dissection. We analyzed all of them for their SELENBP1 expression by immunohistochemistry. Eight triple-paired cases of gastric mucosa, adenoma and adenocarcinoma from the same patient were selected for RT-PCR analysis. RESULTS: There was a progressive decrease in the expression of SELENBP1 from the low-grade dysplasia/adenomas (42/45, 93%) to the high-grade dysplasia/adenomas (29/42, 69%) and finally to the adenocarcinomas (24/64, 37%), (p<0.001). The progressive decrease in the SELENBP1 expression was also evident in the eight paired cases that were analyzed by RT-PCR. CONCLUSIONS: Our findings demonstrate that the SELENBP1 expression is suppressed in gastric epithelial dysplasia/adenomas and adenocarcinomas. The suppression of SELENBP1 was significantly more frequent and severer in the adenocarcinomas than that in the low-grade dysplasia/ adenomas, and this implies that the suppression of SELENBP1 is a late event in gastric carcinogenesis.

Salivary Duct Carcinoma with Mucin Containing Cells: Report of a Case Misdiagnosed as Mucoepidermoid Carcinoma on Fine Needle Aspiration Cytology.: Haeryoung Kim, Hyunki Kim, Hoguen Kim, Jin Kim, Soon Won Hong, Se Hoon Kim; Korean J Cytopathol. 2006;17(1):56-62.

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Abstract PDF: Salivary duct carcinoma (SDC) is a rare primary salivary gland malignancy characterized by histological features similar to those of ductal carcinomas of the breast. It is regarded as a high-grade malignancy associated with frequent local recurrences and early distant metastases that require aggressive treatment. The typical fine needle aspiration cytology (FNAC) findings in SDC include cellular smears showing tumor cells with eccentric pleomorphic nuclei and a granular cytoplasm arranged in flat sheets or cribriform patterns against a necrotic background. However, the presence of mucin-containing cells in SDC has been rarely described. We report the FNAC findings in a patient with histologically confirmed SDC that demonstrated numerous mucin-containing cells and was subsequently misdiagnosed as a high-grade mucoepidermoid carcinoma. Here we discuss the problems involved in distinguishing SDC from high-grade mucoepidermoid carcinoma on the basis of cytologic findings alone.

Adequate Microsatellite Markers for 1p/19q Loss of Heterozygosity of Oligodendroglial Tumors in Korean Patients.: Se Hoon Kim, Hoguen Kim, Tai Seung Kim; Korean J Pathol. 2005;39(1):23-33.

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Abstract PDF: BACKGROUND
It is well known that oligodendrogliomas can be divided into two groups according to the 1p/19q or 1p loss of heterozygosity (LOH) status because oligodendrogliomas with the 1p/19q LOH or the 1p LOH have a better prognosis and chemosensitivity. In this study, we investigated the adequate microsatellite markers for 1p/19q LOH of oligodendroglial tumors in Korean patients.
METHODS
We performed PCR that was based on the LOH test with the 1p (D1S508, D1S199, D1S2734, D1S186 & D1S312) and 19q (D19S219, D19S112, D19S412 & D19S596) microsatellite markers; these were the markers that were recommended by other researchers. We performed this PCR on microdissected paraffin embedded tissue blocks of 67 tumors from 56 cases.
RESULTS
The PCR based LOH analysis revealed that 3 microsatellite markers (D1S508, D1S2734 & D1S186) of 1p and 2 markers (D19S219 & D19S412) of 19q had higher heterozygosity scores than other markers. In addition, chromosomal LOH status using these selective markers showed a statistically significant difference of prognosis for oligodendroglial tumors.
CONCLUSIONS
We can suggest that the microsatellite markers with high heterozygosity scores (D1S508, D1S2734, D1S186, D19S219 and D19S412) would be adequate microsatellite markers for a PCR based LOH test of oligodendroglial tumors in Korean patients.

beta-Catenin Expression in Gastric Carcinogenesis.: Haeyoun Kang, Yon Rak Choi, Hoguen Kim; Korean J Pathol. 2001;35(5):376-382.

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Abstract PDF: BACKGROUND
The molecular pathogenesis of gastric carcinoma is not yet well characterized. The purpose of this study is to assess the role of beta-catenin in gastric carcinogenesis.
METHODS
We analyzed beta-catenin expression using immunohistochemistry on 68 gastric adenomas and 34 gastric adenocarcinomas, and compared the result with pathological and molecular types of tumors and E-cadherin expression.
RESULTS
Nuclear expression of beta-catenin was noted more frequently in gastric adenomas than in carcinomas (40% vs. 21%, 0.05< or = P<1). There was no significant relationship between nuclear beta-catenin expression and histologic degree of adenoma, histologic type of carcinoma or microsatellite instability. E-cadherin expression showed significantly more frequent decrease in the membrane stainability of carcinomas compared to adenomas (P<0.01).
CONCLUSIONS
The frequent nuclear beta-catenin expression in gastric adenomas suggests that the beta-catenin alteration might play an early role in gastric carcinogenesis.

Isolated Polypoid Ganglioneuroma in the Rectum.: Se Hoon Kim, Chang Hwan Choi, Yong Han Paik, Won Ho Kim, Hoguen Kim; Korean J Pathol. 2001;35(4):344-346.

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Abstract PDF: Gastrointestinal ganglioneuroma is a rare benign neoplasm, composed of ganglion cells, nerve fibers, and supporting cells. Ganglioneuromas are presented as isolated polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromas. We have experienced a case of an isolated ganglioneuromatous polyp in the rectum. The patient was a 58-year-old female who had experienced low abdominal discomfort and tenesmus for 6 to 7 months. Colonoscopic examination revealed a polypoid tumor in the rectum. Microscopically, the tumor showed cystic glands, expanded lamina propria, and smooth surface epithelium. Many proliferated ganglion cells with nerve fibers were evident in the lamina propria which was extended to the submucosa.

Expression Pattern of DNA Mismatch Repair Genes in Tumors of Microsatellite Mutator Phenotype.: Jung Jin Kim, Myung Jin Baek, Nam Gyun Kim, Yun Hee Kim, Ji Eun Kim, Hoguen Kim, Chanil Park; Korean J Pathol. 2000;34(9):609-614.

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Abstract PDF: Microsatellite mutator phenotype (MMP) tumors were reported in a subset of gastrointestinal carcinomas. The molecular pathogenesis of MMP tumors shows defects in the DNA mismatch repair genes, and also many germline and somatic mutations were reported in the MMP tumors. However, the detection of genetic defects in the MMP tumors is very difficult, mainly because many genes are included in the DNA mismatch repair genes. This study was undertaken to determine the best strategy for detecting defects in the DNA mismatch repair genes in gastrointestinal carcinomas. One of the effective ways for detecting defects in DNA mismatch repair genes is to screen the MMP tumors and evaluate the products of DNA mismatch repair genes by performing the multiplex RT-PCR method. We have screened the MMP tumors by using 5 microsatellite markers in the 12 cancer cell lines, 120 colon carcinomas and 99 gastric carcinomas and found 6 MMP cell lines, 10 MMP colon cancers, and 9 MMP gastric carcinomas. In addition, we evaluated 6 DNA mismatch repair gene products (hMSH2, hMSH3, hMSH6, hMLH1, hPMS1 and hPMS2) by multiplex RT-PCR analysis and found decreased expression of the DNA mismatch repair genes in 5 (hMSH6 in DLD-1 and HCT-15; hMSH2 in LoVo; hMLH1 and hMSH3 in HCT-116; hMLH1 in SNU-638) out of 6 MMP cell lines. We also found a decreased expression of hMLH1 in 3 out of 10 MMP colon carcinomas, and in 6 out of 9 MMP gastric carcinomas. Our results indicate that the expression analysis of the DNA mismatch repair genes by multiplex RT-PCR method can reduce the number of genes subjected to mutational analysis and is convenient for screening the responsible DNA mismatch repair genes.

Bleeding from Dieulafoy's Vascular Malformation of the Proximal Ileum: A case report .: Hee Jung Kim, Jun Keun Jung, Young Min Suh, Kyung Sook Kim, Hoguen Kim; Korean J Pathol. 1999;33(12):1207-1210.

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Abstract PDF: Dieulafoy's vascular malformation is a rare cause of massive gastrointestinal bleeding. Most often it occurs in stomach within 6 cm from the gastroesophageal junction. Only a few cases have been reported to occur in the small intestine and colon. Occasionally, Dieulafoy's lesion of small intestine is difficult to recognize because of rarity, a paucity of symptoms and negative findings on barium studies. Therefore, this lesion needs to be considered in a patient with massive lower gastrointestinal bleeding. We report a case of Dieulafoy's vascular malformation in ileum 2 m proximal to ileocecal value in a 41-year-old woman who visited emergency clinic because of hematemesis, dizziness and vomiting. Small intestine revealed a wide-caliber artery within the submucosa showing intimal thickening, medial muscular hypertrophy and thrombosis.

Gastrointestinal Polyposis in Koreans: A Nationwide Survey of Clinicopathologic Analysis of 112 Surgically Resected Cases.: Mee Soo Chang, Hoguen Kim, Woo Ho Kim, Chan Il Park, Eun Kyung Hong, Han Kyeom Kim, In Soo Suh, Byung Kee Kim, Ja June Jang, Woon Sub Han, Hyung Sik Shin, So Young Jin, Dae Young Kang, Yong Il Kim; Korean J Pathol. 1998;32(6):404-412.

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Abstract: Gastrointestinal polyposis (GIP) is a rare disease characterized by formation of the numerous polyps in the gastrointestinal tract and presenting several extraintestinal manifestations. Most of the diseases are transmitted in an autosomal dominant pattern. In Korea, the epidemiological study as well as the pathological analysis of the GIP is not well established. We therefore analysed 38 items of GIP using surgically resected specimens. The materials in this study were collected from the 12 institutions and case reports in Korean literature between 1980 and 1991. The clinicopathologic findings were reevaluated by several members of the study group for gastrointestinal pathology. The results are as follows: (1) A total of 112 cases were included in this study: 83 cases were collected from 12 institutions and 29 cases were collected from Korean literature. The cases were classified as familial adenomatous polyposis (FAP), 59 cases; Gardner's syndrome, 3 cases; juvenile polyposis, 12 cases; Peutz-Jeghers syndrome, 35 cases; multiple colonic adenomas, 3 cases. (2) Among 59 cases of FAP, the range of age at operation was 14 to 61 years, and a family history was positive in 25 cases. The number of polyps in colorectum was 100~8,000. Of the 37 cases in which the examination of polyp density was available, 16 cases (43%) showed the highest density in the rectum and the sigmoid colon. The carcinomatous change within polyp(s) was present in 18 cases (31%), and associated advanced single or multiple colonic carcinomas existed in 37 cases (63%). Twenty-six (45%) tumors out of total 58 carcinomas were in the rectum. Twenty-five patients were evaluated for the upper gastrointestinal lesions, and 11 patients (44%) had pathologic lesions; multiple fundic gland polyps in 3 cases (12%), gastric and duodenal adenomas in 2 cases (8%), gastric adenomas in 2 cases (8%), duodenal adenomas in 2 cases (8%), gastric carcinoma and adenoma in 1 case (4%), gastric carcinoma in 1 case (4%). (3) Among 3 cases of Gardner's syndrome, the range of age at operation was 25 to 31 years, a family history was identified in 2 cases. One case was associated with an advanced colonic carcinoma and carcinomatous change within polyp. Extra gastrointestinal lesions were sebaceous cyst, epidermal cyst, osteoma and desmoid tumor. (4) Among 12 juvenile polyposis, the range of age at operation was 8 to 51 years and 5 patients had a family history. The carcinomatous change within polyp was found in 2 cases (17%) and associated advanced colonic carcinoma was in 4 cases (33%). The associated different type of polyps was tubular adenomas in 9 cases (75%), hyperplastic polyps in 4 cases (33%) and villous adenomas in 2 cases (17%). (5) Among 35 Peutz-Jeghers syndrome, the range of age at first operation was 6 to 42 years, family history was positive in 11 cases. The carcinomatous change within polyp was found in 1 case (3%), and associated advanced colonic carcinoma in 1 case (3%). The epithelial misplacement was observed in 4 cases (11%), and tubular or villous adenomatous feature in 4 cases (11%). In summary, the most frequent GIP for the surgical resection in Korea is FAP and the FAP is associated with high incidence of coexisting advanced and intramucosal carcinomas. Hamartomatous polyposis syndromes, such as juvenile polyposis and Peutz-Jeghers syndrome are another frequent disease for the surgical resection and are also associated with an increased risk of cancer.

Grading System for Gastric Epithelial Proliferative Diseases Standardized Guidelines proposed by Korean Study Group for Pathology of Digestive Diseases.: Hoguen Kim, So Young Jin, Ja June Jang, Woo Ho Kim, Sang Yong Song, Kyu Rae Kim, Eun Sil Yu, Hyung Sik Shin, Han Kyeom Kim, Jin Hee Sohn, Eun Kyung Hong, Youn Wha Kim, Jin Sook Jeong, Chang Jin Kim, Shin Eun Choi, In Suh Park, Chan Il Park, Yong Il Kim; Korean J Pathol. 1997;31(5):389-400.

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Abstract PDF: The assessment of epithelial changes in gastric mucosal biopsies has been one of the major problems caused by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, members of the Study Group for Pathology of Digestive Diseases reviewed microslides of 50 gastric lesions showing varying degrees of mucosal abnormality and reached the following consensus; 1) the proliferating gastric epithelium can be divided into hyperplastic and neoplastic; 2) the term "dysplasia" is reserved for the microscopic epithelial changes that are unequivocally neoplastic; 3) Biopsy specimens can be categorized as regenerative(negative for dysplasia), indefinite(questionable dysplasia), positive(positive for dysplasia) and overt carcinoma; 4) The positive category can be divided into two subgroups, high grade dysplasia and low grade dysplasia. Criteria for each grade are presented and discussed. We offer these guidelines for establishing the correct diagnosis of the gastric mucosal biopsy specimens and for prospective studies.

Pathologic Characteristics of Colorectal Cancers with DNA Replication Errors.: Hoguen Kim, Yoon Mi Jeen, Jeong Yeon Shim, Chanil Park; Korean J Pathol. 1995;29(5):590-595.

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Abstract: Unstable microsatellite repeat sequences or DNA replication errors(RER) due to defective mismatch repair genes have been reported in a subset of sporadic colorectal tumors and in most tumors of patients of hereditary nonpolyposis colorectal carcinoma(HNPCC). To elucidate the clinicopathological correlation of these RER-positive cancers, we examined 16 cases of colorectal carcinoma of different histologic subtypes(6 cases of carcinoma with no gland formation, 5 cases of mucinous carcinoma and 5 cases of gland forming carcinoma). We detected RER in five cases. The patients with RER-positive cancers had a marked preponderance of carcinoma with no gland formations out of 6 carcinomas with no gland formation were RER-positive cancers) and of cancers proximal to splenic flexure(all of the RER-positive cases were proximal colon carcinomas). We conclude that RER-positive cancers have wiique pathologic features that may be useful for the screening and counselling of patients with hereditary colon cancers.

Malignant Endometrioid Adenofibroma of the Ovary: A case report.: Tae Jung Jang, Soon Hee Jung, Kyu Rae Kim, Hoguen Kim; Korean J Pathol. 1990;24(4):497-501.

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Abstract PDF: Ovarian endometrioid adenofibroma is rare and characterized by prominent stroma. Its histologic classification is controversial but the malignant counterpart is distinguished from the borderline by the presence of confluent growth pattern of epithelium with invasion of the stroma by the endometrioid cells. A fifty-year-old woman was admitted with one month history of abdominal enlargement. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed under the clinical diagnosis of ovarian malignancy. Grossly, the righy ovary had round, encapsulated, solid and whitish gray mass which measured 9 cm in the greatest dimension and showed peripheral small cysts. Microscopic examination revealed that the tumor consisted of endometria type glands set in fibrous stroma. The glands varied from tubules to cysts and the lining cells showed complicated architectural pattern with occasional papillary infoldings, atypical mitosis and malignant nuclear characteristics. Some cysts of glands showed intraluminal mucin products. Stromal invasions by individual epithelial cells showing malignant characteristics were often found. A brief summary of the histopathologic aspect of this tumor is presented together with review of literatures.

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