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Volume 44(3); June 2010
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Original 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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AbstractAbstract 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.
Expression of Raf-1 Kinase Inhibitory Protein in Extrahepatic Bile Duct Carcinoma.
Hyun Soo Kim, Gou Young Kim, Sung Jig Lim, Youn Wha Kim
Korean J Pathol. 2010;44(3):234-242.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.234
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  • 6 Citations
AbstractAbstract PDF
BACKGROUND
Raf-1 kinase inhibitory protein (RKIP) recently has been identified as a metastasis suppressor in a variety of human carcinomas. The prognostic significance of RKIP expression in extrahepatic bile duct (EBD) carcinoma has not been studied. The aims of the current study were to evaluate RKIP expression and to determine the prognostic significance of RKIP expression in EBD carcinoma.
METHODS
Immunohistochemical staining for RKIP was performed for 131 cases of EBD carcinoma. The associations of RKIP expression with clinicopathologic parameters and patient outcomes were examined. Multivariate logistic regression analysis was used to identify independent predictive parameters for lymphovascular invasion and nodal and distant metastases.
RESULTS
Loss of RKIP expression was observed in 55.0% (72/131) of cases. EBD carcinoma had significantly lower RKIP immunoreactivity than normal EBD (p < 0.001). Loss of RKIP expression was significantly associated with lymphatic invasion (p = 0.030) and nodal metastasis (p = 0.036), but it was not found to be a significant prognostic predictor for overall, disease-free or distant metastasis-free survival. In addition, loss of RKIP expression was an independent predictor for lymphatic invasion (p = 0.027).
CONCLUSIONS
These results suggest that RKIP may play a role in the suppression of lymphatic invasion and nodal metastasis in EBD carcinoma.
Microvessel and Lymphatic Vessel Density and VEGFR-3 Expression of Papillary Thyroid Carcinoma with Comparative Analysis of Clinicopathological Characteristics.
Harin Cheong, Hanna Kang, Hyung Kyung Kim, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo
Korean J Pathol. 2010;44(3):243-251.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.243
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
This study was done to see if there were correlations between anatomic and molecular parameters such as microvessel density (MVD), lymphatic vessel density (LVD), and vascular endothelial growth factor receptor (VEGFR)-3 expression and various clinical parameters for papillary thyroid carcinomas of size > 1.0 cm (PTCs) and size < or = 1.0 cm (papillary thyroid microcarcinomas, PTMCs). PTMCs were divided into two subgroups (0-5 mm and 6-10 mm).
METHODS
We analyzed 197 thyroid carcinomas including 113 PTCs and 84 PTMCs. Tissue samples form 30 patients from each group matched for clinical characteristics were selected for immunostaining.
RESULTS
Although PTCs and PTMCs showed significant differences in clinical characteristics, they did not show significant difference in MVD, LVD, or VEGFR-3 expression. There was a significantly higher LVD in the PTMC subgroup with the larger tumors but no difference in clinical characteristics. LVD was higher in patients > 45 years old (more apparent in the PTC group) and LVD had suggestive correlations with multicentricity and extrathyroidal extension depending on analytic conditions.
CONCLUSIONS
Since LVD showed variable correlations with clinical variables for papillary carcinoma of the thyroid depending on analytic conditions, the individually planned treatments based on overall clinicopathological factors are advised.
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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  • 3 Citations
AbstractAbstract 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.
Comparison of Various Detection Methods of Mycobacterium Species in Formalin-Fixed Paraffin-Embedded Tissue with Chronic Granulomatous Inflammation.
Hyun Seung Lee, Hyoungnam Lee, Soyoung Im, Yun Su Lee, Kyo Young Lee, Yeong Jin Choi
Korean J Pathol. 2010;44(3):259-266.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.259
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR).
METHODS
We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases.
RESULTS
Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%).
CONCLUSIONS
RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.
The Interobserver Variability for Diagnosing Pulmonary Carcinoid Tumor.
Chang Hun Lee, Hee Kyung Chang, Hyoun Wook Lee, Dong Hoon Shin, Mee Sook Roh
Korean J Pathol. 2010;44(3):267-271.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.267
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  • 6 Citations
AbstractAbstract PDF
BACKGROUND
Although the grade of pulmonary carcinoid tumor is routinely reported in pathology practice, there is a paucity of data on the level of agreement between pathologists.
METHODS
Data for 30 cases of surgically resected pulmonary tumors diagnosed as carcinoid tumors (19 typical carcinoids [TCs] and 11 atypical carcinoids [ACs]) were retrieved from four university hospitals. These cases were independently evaluated by five pathologists and were classified according to the 2004 World Health Organization (WHO) classification. Agreement was regarded as "unanimous" if all five pathologists agreed, and as a "majority" if four agreed. The kappa statistic was calculated to measure the degree of agreement between pathologists.
RESULTS
Unanimous agreement was achieved for 50.0% and a majority agreement for 83.3% of the 30 cases. The range of the kappa values extended from 0.37 to 0.89. After a consensus meeting, there was disagreement between the original diagnosis by each institute and the consensus diagnosis by the five pathologists for 40.0% of the 30 cases. Based on the consensus diagnosis, the agreement was greater for TCs than that for ACs.
CONCLUSIONS
Discriminating carcinoid tumors is subject to interobserver variability. This study indicates that there is a need for more careful standardization and application of diagnostic criteria for making the diagnosis of pulmonary carcinoid tumor.
Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen Responsiveness In Vitro.
Eun Ju Lee, Prati Bajracharya, Dong Mok Lee, Kyung Hyun Cho, Keuk Jun Kim, Young Kyung Bae, Mi Jin Kim, Ki Ho Lee, Hang Jin Kim, Gun Ho Song, Sang Sik Chun, Inho Choi
Korean J Pathol. 2010;44(3):272-283.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.272
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  • 3 Citations
AbstractAbstract PDF
BACKGROUND
Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women. The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression.
METHODS
Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma. The data was confirmed at protein level by tissue microarray.
RESULTS
Gene microarray analysis revealed 792 upregulated genes in leiomyoma. Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4alpha2], insulin-like growth factor binding protein 5 [IGFBP5], tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples. Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-alpha, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4alpha2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group. PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate. Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell.
CONCLUSIONS
This observation implies the importance of the whole tissue context including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.
Immunohistochemical Array for Clear Cell Type Mucoepidermoid Carcinoma.
Yeon Sook Kim, Sang Shin Lee, Ji Yong Song, Eun Cheol Kim, Suk Keun Lee
Korean J Pathol. 2010;44(3):284-294.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.284
  • 2,580 View
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
The protein expression profile of clear cell type mucoepidermoid carcinoma (MEC) is not well known.
METHODS
We examined a case of clear cell type MEC by immunohistochemical (IHC) array using 59 antibodies against oncoproteins, proliferation-related proteins, apoptosis-related proteins, growth factor-related proteins, angiogenesis-related proteins, and matrix proteins.
RESULTS
MEC tumor cells showed 40 to 60% more expression of BCL-2 and cyclin-dependent kinase 4 than normal gingival tissue, and 20-40% more expression of BCL-2-associated agonist of cell death, deleted in malignant brain tumors 1, E-cadherin, eIF5A, hypoxia-inducible factor, vimentin, and Wnt-1. Expression of other proteins, including p53, epidermal growth factor receptor, proliferating cell nuclear antigen, survivin, carcinoembryonic antigen, beta-catenin, poly-ADP ribose-polymerase, etc. were relatively weak in MEC tumor cells.
CONCLUSIONS
The IHC array for our MEC contained strong oncogenic signals involving Wnt-1/adenomatous polyposis coli, tumor necrosis factor a/signal transducer and activator of transcription 3/BCL-2, and pAKT pathways, signals that could result in the prolonged survival of clear tumor cells.
Quality Control Program for Fresh Frozen Tissue and Its Results of Chonbuk National University Hospital National Biobank of Korea.
Shin Young Park, Hyun Ah Baek, Hyoung Jong Kwak, Sang Hyun Hong, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung
Korean J Pathol. 2010;44(3):295-301.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.295
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Molecular tools for tissue profiling generally require collection of fresh frozen tissues (FFT) as sources of high-quality DNA and RNA. Nowadays, researchers carry out large-scale, multi-center studies and they request inter-institutional minimal intrinsic bias, some fundamental similarities, and the same standardized and validated procedures.
METHODS
This study reports standardized quality control procedure for fresh frozen tissue of the National Biobank of Korea.
RESULTS
The main procedures for quality control for FFT are as follows: records related to sample collection such as labeling of samples, transport temperature, lag time from excision of tissue to freezing, and sample size were reviewed for all fresh frozen samples. The stability of RNA and DNA in fresh frozen tissue was evaluated for 3% of collected samples and purity was assessed (ratio of the absorbance at 260 and 280 nm) as was integrity (agarose gel electrophoresis). Stained hematoxylin and eosin sections were reviewed by a pathologist to confirm the diagnosis and to assess how representative the frozen sample was.
CONCLUSIONS
We introduced that the quality-control criteria for fresh frozen tissue of the NBK. We expect that this study contributes to standardization of collection, storage, and quality control of fresh frozen tissue.
Metastatic Carcinomas to the Sinonasal Tract.
Eun Ju Kim, Bong Jae Lee, Kyung Ja Cho
Korean J Pathol. 2010;44(3):302-307.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.302
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Metastases to the sinonasal tract are rare but occur for many malignancies. The demographics of sinonasal metastases in Korea aren't well known.
METHODS
Nine cases of metastases to the sinonasal tract identified at Asan Medical Center from January, 1995 to December, 2007 were reviewed.
RESULTS
Metastatic carcinomas accounted for 2.4% of sinonasal malignancies and 4.7% of carcinomas. Six kinds of cancer metastasized to the sinonasal tract. They included hepatocellular carcinomas (nasal cavity and maxillary sinus), colonic adenocarcinomas (sphenoid sinus and maxillary sinus), clear cell renal cell carcinoma (nasal cavity), pulmonary small cell carcinoma (nasal cavity), follicular carcinoma of thyroid (sphenoid sinus), and breast ductal carcinoma (maxillary sinus). Primary sites had been known in 7 cases, but follicular carcinoma and one adenocarcinoma were diagnosed after sinus metastases. Histologically, they had ill-defined borders and involved both mucosae and bones. Microscopic findings were not different from those for the primary tumors.
CONCLUSIONS
The pattern of sinonasal metastases in Korea are different from western data regarding incidence, site, and type, with hepatocellular carcinoma and the nasal cavity being the most common type and site, respectively. Awareness of the possibility of metastases and their pattern is encouraged when examining sinonasal tumors.
The Frequency of BRAF Mutation in Very Small Papillary Thyroid Carcinomas.
Taeeun Kim, Ji Hyun Roh, Hee Jung Park, Jee Eun Kwon, So Young Kang, Yoon La Choi, Young Lyun Oh
Korean J Pathol. 2010;44(3):308-314.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.308
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  • 3 Citations
AbstractAbstract PDF
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid and BRAF (V600E) is the most frequent genetic alteration in PTCs. The aim of this study was to investigate the frequency of BRAF mutation, especially in very small PTCs.
METHODS
We analyzed the presence of the BRAF mutation in PTCs in subgroups defined by tumor size (0.5 cm intervals).
RESULTS
Of 140 patients, 85 (60.7%) showed a BRAF mutation. The frequency of BRAF mutation in the subgroup was: 45/70 (64.3%) in tumors less than 0.5 cm in size, 18/28 (64.3%) in 0.6-1 cm tumors, 10/22 (45.5%) in 1.1-1.5 cm tumors, and 12/20 (60.0%) in 1.6-2 cm tumors. There was no statistically significant association between BRAF mutation and tumor size (p = 0.44). Similarly, BRAF mutation was not statistically related to age, sex, stage, perithyroidal extension or lymph node metastasis. On multivariate logistic regression analysis, tumor sizes larger than 0.5 cm were associated with lymph node metastasis (odds ratio, 3.79; 95% confidence interval, 1.81 to 7.91; p < 0.01).
CONCLUSIONS
The BRAF mutation is not related to tumor size even in very small PTCs. The similar frequency of BRAF mutation in very small PTCs suggests that the BRAF mutation is a very early event in the tumorigenesis of PTCs.
Utility of Promoter Hypermethylation for Differentiating Malignant and Benign Effusions in Liquid-Based Cytology Specimens.
Ga Eon Kim, Jo Heon Kim, Yeong Hui Kim, Chan Choi, Ji Shin Lee
Korean J Pathol. 2010;44(3):315-321.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.315
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Making the cytologic differentiation between benign and malignant effusions can be difficult. Because promoter hypermethylation of tumor suppressor genes is a frequent epigenetic event in many human cancers, it could serve as a marker for the diagnosis of cancer. The aim of this study was to investigate the feasibility of detecting promoter hypermethylation as a diagnostic tool with using liquid-based cytology samples for differentiating between malignant and benign effusions.
METHODS
A multiplex, nested, methylation-specific polymerase chain reaction analysis was used to examine promoter methylation of 4 genes (retinoic acid receptor-beta, [RAR-beta], adenomatous polyposis coli [APC], Twist and high in normal-1 [HIN-1]) in malignant (n = 85) and benign (n = 31) liquid-based cytology samples.
RESULTS
The frequencies of hypermethylation of RAR-beta, APC, Twist and HIN-1 were significantly higher in the malignant effusions than in the benign effusions (p < 0.001 for each). On the receiver-operating characteristic analysis, the area under the curve (AUC) for APC was the greatest. The AUC for the best two-gene combination (APC/HIN-1) was not statistically different from the AUC for the best individual tumor suppressor gene (APC).
CONCLUSIONS
This study suggests that promoter methylation analysis on residual liquid-based effusion samples may be a feasible approach to detect malignant effusions, and that APC is the best marker for differentiating between malignant and benign effusions.
Case Reports
Malignant Fibrous Histiocytoma Arising in a Mature Cystic Teratoma of the Ovary: A Case Report.
Soyoung Im, Sun Mi Lee, Ji Han Jung, Hyun Joo Choi, Jinyoung Yoo, Seok Jin Kang, Kyo Young Lee
Korean J Pathol. 2010;44(3):322-325.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.322
  • 2,318 View
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AbstractAbstract PDF
A 50-year-old female patient presented with anorexia and weight loss. Pelvic computed tomography revealed a 12.5 x 7.3 cm heterogeneous mass in the left ovary. About 30% of the tumor was occupied by a mature cystic teratoma. The remaining solid portion was composed of fibrous and histiocytic elements, arranged in storiform patterns admixed with bizarre giant cells. The mitotic index was 8 per 10 high power fields, including atypical mitoses. The only immunopositivity was for vimentin. The tumor was diagnosed as a malignant fibrous histiocytoma arising in a mature cystic teratoma. To the best of our knowledge, this is only the third such case in the English language literature.
Glomus Tumor of the Sinonasal Tract: Two Case Reports and a Review of Literature.
Young Wha Koh, Bong Jae Lee, Kyung Ja Cho
Korean J Pathol. 2010;44(3):326-329.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.326
  • 2,568 View
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  • 7 Citations
AbstractAbstract PDF
Herein we describe two cases of nasal glomus tumor. Histological findings were typical, save for one which was quite large (3.1 cm in its greatest dimension) with an invasive growth pattern and increased ki-67 labeling index (up to 10%). These features raised a red flag of similarity to a recently described "invasive glomus tumor of nasal cavity", suggesting a more aggressive form of glomus tumor. However, objective criteria for this possibility is lacking at present and more similar case studies are needed to establish a truly aggressive form of glomus tumor.
Acute Appendicitis Associated with Aspergillosis in a Leukemia Patient: A Case Report.
Bong Hee Park, Jae Hee Suh, Hye Jeong Choi, Hee Jeong Cha, Chang Woo Nam, Young Min Kim
Korean J Pathol. 2010;44(3):330-332.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.330
  • 2,575 View
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  • 5 Citations
AbstractAbstract PDF
Herein we describe a rare case of acute appendicitis associated with localized aspergillosis in an 8-year-old boy with acute lymphoblastic leukemia. During chemotherapy, the patient complained of mild abdominal pain in the peri-umbilical area and displayed an increased C-reactive protein level. Abdominal ultrasonography disclosed appendicitis and consequently an appendectomy was done. Histologically, acute appendicitis and Aspergillus hyphae were identified in the lumen and necrotic mucosa. However, there was no evidence of systemic aspergillosis. While aspergillosis is a common fungal infection in immunocompromised patients treated with chemotherapy, acute appendicitis associated with localized aspergillosis without systemic infection is a very rare occurrence.

JPTM : Journal of Pathology and Translational Medicine