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Volume 45(5); October 2011
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Original Articles
The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients.
Tae Hwa Baek, Joo Heon Kim, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Hyun Ki Soon, Chang Nam Kim, Che Myong Ko, Dong Wook Kang
Korean J Pathol. 2011;45(5):445-454.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.445
  • 2,881 View
  • 27 Download
AbstractAbstract PDF
BACKGROUND
Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs).
METHODS
Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated.
RESULTS
CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis.
CONCLUSIONS
Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.
MGMT Gene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour.
Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim
Korean J Pathol. 2011;45(5):455-462.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.455
  • 2,909 View
  • 11 Download
  • 1 Citations
AbstractAbstract PDF
BACKGROUND
The aim of this study was to determine whether pyrosequencing (PSQ) might be useful to achieve O6-methyl guanine methyltransferase (MGMT) promoter methylation using 1- to 13-year-old archival tissues as a clinical biomarker in routine practice.
METHODS
The study included 141 formalin-fixed paraffin-embedded (FFPE) glial tumors from the archives of the Pathology Department from 1997-2010.
RESULTS
The average percentage of methylation (MP) of the 141 cases was 14.0+/-16.8%, and methylated cases were 32.3+/-14.9%. The average MP of each year did not show a linear increasing or decreasing pattern according to the age of the FFPE block (p=0.771). The average MP of methylated glioblastomas was 35.8+/-14.7%, 31.8+/-15.5% for anaplastic astrocytomas, and 22.4+/-15.1% for astrocytoma. A tendency was observed toward an increasing pattern of average MP with World Health Organization (WHO) grade (p=0.063) in astrocytic tumors. A correlation was observed between average MP and WHO grade (p=0.038) and a bimodal distribution was observed between the methylated and unmethylated cases, using a 9% cut-off value (p<0.001).
CONCLUSIONS
The results showed that a quantitative approach for MGMT promoter methylation yielded a 100% success rate for FFPE tissues from archives. PSQ can be used in a retrospective trial, but the cut-off value and calculation method should be further validated.
Expression of Hepatocyte Growth Factor/c-met by RT-PCR in Meningiomas.
Na Rae Kim, Yang Seok Chae, Weon Jeong Lim, Seong Jin Cho
Korean J Pathol. 2011;45(5):463-468.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.463
  • 2,626 View
  • 22 Download
AbstractAbstract PDF
BACKGROUND
Hepatocyte growth factor (HGF) is a potent mitogenic cytokine. C-met protein, which is known to be the HGF receptor has transmembrane tyrosine kinase activity and is encoded by the c-met oncogene. The HGF/c-met signaling pathway may play various roles in the carcinogenesis of various organs.
METHODS
We examined HGF and c-met mRNA expression by utilizing reverse transcription polymerase chain reaction on 40 surgically resected intracranial meningiomas (25 benign, 10 atypical, and 5 anaplastic cases).
RESULTS
An HGF overexpression was detected in 28%, 50%, and 80% of the benign, atypical and anaplastic meningiomas, respectively; a high expression of HGF or the coexpression of HGF/c-met was detected in the high grade meningiomas (the atypical and anaplastic cases, p=0.046, p=0.014). An HGF expression was statistically significant in the recurrent meningiomas (p=0.003), and HGF expression was significantly lower than c-met mRNA expression in benign meningiomas (p=0.034).
CONCLUSIONS
There was no correlation between histologic subtypes and HGF/c-met expression. Determination of HGF expression can be used as a molecular predictor for recurrence of meningioimas. These results suggest that HGF and c-met expression in meningiomas may be associated with anaplastic progression.
CpG Island Methylation According to the Histologic Patterns of Early Gastric Adenocarcinoma.
Junjeong Choi, Mee Yon Cho, So Young Jung, Khalilullah Mia Jan, Hyun Soo Kim
Korean J Pathol. 2011;45(5):469-476.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.469
  • 2,488 View
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Although the importance of aberrant DNA methylation in the development of gastric adenocarcinoma has been described, the mechanism of pathogenesis has not been revealed yet. We quantitatively analyzed methylation of four CpG islands and one repetitive DNA element, according to the histologic features of adenocarcinoma with precursor lesions.
METHODS
We divided the cases as adenocarcinoma with intestinal type precursors (type A, n=19 cases) and adenocarcinoma with diffuse type precursors (type B, n=19 cases). We micro-dissected tumor cells and matched non-neoplastic gastric mucosa from the hematoxylin and eosin-stained slides.
RESULTS
A total of 20 CpG sites of long interspersed nucleotide element-1 (LINE1), RAR-related orphan receptor alpha (RORA), Kruppel-like factor 7 (KLF7), mutL homolog 1 (MLH1), MINT25, and CD133 were analyzed. Methylation was determined by bisulfate-pyro-sequencing, and hypomethylation of LINE1 and CD133 was noted in the tumors, compared to the levels in the non-neoplastic gastric mucosa (p=0.014 and p=0.015, respectively). A statistically different methylation pattern of CpG sites at CD133 and KLF7 was noted only in type B lesions, compared to that in matched non-neoplastic gastric mucosa (p=0.027 and p=0.043, respectively).
CONCLUSIONS
Given that aberrant methylation occurs in a relatively early phase of carcinogenesis, different patterns of methylation may determine the carcinoma phenotype. However, further large-scale study is required to clarify the significance of this difference.
CD56 and High Molecular Weight Cytokeratin as Diagnostic Markers of Papillary Thyroid Carcinoma.
Mi Kyung Shin, Jeong Won Kim, Young Su Ju
Korean J Pathol. 2011;45(5):477-484.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.477
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  • 8 Citations
AbstractAbstract PDF
BACKGROUND
The incidence of papillary thyroid carcinoma (PTC) has been increasing recently and a precise diagnosis is essential for optimal treatment. Ancillary immunohistochemical stains are important for diagnosing some difficult cases.
METHODS
The dignostic value of CD56, high molecular weight cytokeratin (HMCK), galectin-3 (GAL3), and cytokeratin 19 (CK19) were evaluated to distinguish PTC from other benign thyroid lesions (BTL). We studied 23 cases of papillary thyroid overt carcinomas, 57 papillary thyroid microcarcinomas, five follicular adenomas, five cases of Hashimoto's thyroiditis, and 12 nodular hyperplasias.
RESULTS
The statistical analysis showed significantly different expressions of CD56, HMCK, GAL3, and CK19 in PTC vs other BTL. The diagnostic specificity of HMCK and CD56 (90.9% and 72.7%, respectively) was higher than that of GAL3 and CK19 (50.0% and 36.4%, respectively). However, the sensitivity of HMCK and CD56 detection (92.5% and 95.0%, respectively) was lower than that of GAL3 and CK19 (98.8% and 100.0%, respectively). The combined use of CD56, HMCK, GAL3, and CK19 showed 87.5% sensitivity, 100.0% specificity, and 100.0% positive predictive value in differentiating PTC from other BTL.
CONCLUSIONS
Although the differential diagnosis of thyroid follicular lesions are based on histological and cytomorphological criteria, CD56 and HMCK might be useful markers for diagnosing PTC.
14-bp Insertion/Deletion Polymorphism of the HLA-G Gene in Osteosarcoma Patients.
Ahrim Moon, Su Kang Kim, Joo Ho Chung, Ki Yong Na, Liliana G Olvi, Eduardo Santini-Araujo, Youn Wha Kim, Yong Koo Park
Korean J Pathol. 2011;45(5):485-490.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.485
  • 2,708 View
  • 15 Download
  • 1 Citations
AbstractAbstract PDF
BACKGROUND
The major histocompatibility complex class I, G (human leukocyte antigen-G [HLA-G]) gene plays a vital role in the suppression of immune responses. Recently, a number of studies have reported an association between HLA-G and diseases (pregnancy complications, organ transplantation, and tumors). Some of the studies have revealed that the 14-bp insertion/deletion polymorphism might be associated with various diseases. The aim of the present study was to explore a possible influence of the 14-bp insertion/deletion polymorphism on osteosarcoma.
METHODS
Genomic DNA was extracted from 75 formalin-fixed, paraffin-embedded tumor tissues derived from patients with conventional osteosarcoma (OSA) and 183 peripheral blood samples of healthy controls. Fifty-eight cases were South Korean patients with OSA and 17 cases were Argentine patients with OSA. The HLA-G 14-bp insertion/deletion polymorphism at exon 8 of the HLA-G locus was analyzed by polymerase chain reaction.
RESULTS
There was a significantly different distribution profile for the 14-bp genotypes between the Korean OSA and Korean control groups. Specifically, there were more heterozygote 210 bp/224 bp genotypes in the Korean OSA group when compared to the Korean control group (62.1% vs 40.4%, p=0.002).
CONCLUSIONS
The results suggest that HLA-G heterozygote patients may be more susceptible to OSA in the Korean population.
Idiopathic Duct Centric Pancreatitis in Korea: A Clinicopathological Study of 14 Cases.
Hyo Jeong Kang, Tae Jun Song, Eunsil Yu, Jihun Kim
Korean J Pathol. 2011;45(5):491-497.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.491
  • 2,967 View
  • 14 Download
AbstractAbstract PDF
BACKGROUND
Idiopathic duct centric pancreatitis (IDCP) is a subtype of autoimmune pancreatitis (AIP) that is histologically characterized by granulocytic epithelial lesion and scarce IgG4-positive cells. This subtype of AIP has not been documented in Asian countries.
METHODS
We reviewed 38 histologically confirmed AIP cases and classified them into lymphoplasmacytic sclerosing pancreatitis (LPSP) and IDCP. Then, clinicopathological characteristics were compared between LPSP and IDCP.
RESULTS
Fourteen cases (36.8%) were IDCP. IDCP affected younger patients more than LPSP. IDCP was associated with ulcerative colitis in 35.7% of cases, whereas LPSP was associated with IgG4-related sclerosing diseases such as cholangitis, retroperitoneal fibrosis or sialadenitis in 41.7% of cases. IDCP was microscopically characterized by neutrophilic ductoacinitis with occasional granulocytic epithelial lesions, whereas LPSP was characterized by storiform inflammatory cell-rich fibrosis and obliterative phlebitis. IgG4-positive cells were not detected in any IDCP case but more than 20 IgG4-positive cells per high-power-field were invariably detected in LPSP cases. All patients with IDCP responded dramatically to steroids without recurrence, whereas 33.3% of patients with LPSP developed recurrences.
CONCLUSIONS
IDCP is clinicopathologically distinct from LPSP and can be diagnosed when neutrophilic ductoacinitis or granulocytic epithelial lesions are observed in a pancreatic biopsy under the appropriate clinical setting.
Diagnostic Utility of the JAZF1/JJAZ1 Gene Fusion in Endometrial Stromal Sarcomas and Their Histologic Variants.
Sang Ryung Lee, Joon Seon Song, Ga Hye Kim, Jene Choi, Hyung Kyoung Kim, Yonghee Lee, Kyu Rae Kim
Korean J Pathol. 2011;45(5):498-505.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.498
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AbstractAbstract PDF
BACKGROUND
The diagnosis of endometrial stromal sarcoma (ESS) is often difficult in cases showing diverse histological differentiation or in undifferentiated endometrial sarcoma (UES). Recently, JAZF1/JJAZ1 gene fusion has been described as a defining feature of low-grade ESS (LGESS). However, its prevalence is variably reported, and the diagnostic utility has rarely been examined for cases showing various histological differentiation.
METHODS
To test the diagnostic utility of JAZF1/JJAZ1 gene fusion in difficult cases, we compared the prevalence of the JAZF1/JJAZ1 fusion gene in LGESS with and without histological differentiation.
RESULTS
The JAZF1/JJAZ1 fusion transcript was detected in 18 of 21 LGESS (85.7%), including 14 classical LGESS (93%), four LGESS with diverse histological differentiation (67%), and two with UES (28.6%). Positive cases included two LGESS with sex cord-like differentiation, one with osseous differentiation, and two UES. LGESS showing smooth muscle differentiation revealed the fusion transcript only in the classic area. Direct sequencing analysis of two LGESS revealed a previously reported breakpoint at t(7;17)(p15;q21).
CONCLUSIONS
The JAZF1/JJAZ1 fusion gene was identified in a significant proportion of LGESS showing secondary histological differentiation except in cases with smooth muscle differentiation. Thus, this fusion gene may be useful to confirm the diagnosis in difficult cases of LGESS.
Histologic Parameters Predicting Survival of Patients with Multiple Non-small Cell Lung Cancers.
Joo Young Kim, Hee Jin Lee, Jun Kang, Se Jin Jang
Korean J Pathol. 2011;45(5):506-515.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.506
  • 2,368 View
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AbstractAbstract PDF
BACKGROUND
In multiple lung cancers (MLCs), distinction between intrapulmonary metastases and multiple primary tumors is important for staging and prognosis. In this study, we have investigated histopathologic prognostic factors of patients with MLCs.
METHODS
Histologic subtype, size differences, lobar location, lymphovascular invasion (LVI), size of the largest tumor, nodal status, number of tumors, morphology of tumor periphery, and immunohistochemical profiles using eight antibodies, were analyzed in 65 patients with MLCs.
RESULTS
There was no significant difference in the survivals of patients with multiple primary tumors and intrapulmonary metastases, as determined by the Martini-Melamed criteria (p=0.654). Risk grouping by four histologic parameters, LVI, margin morphology, size differences, and lobar locations of paired tumors were prognostic. The patients with one or two of aforementioned parameters had significantly longer survival than those with three or four parameters (p=0.017). In patients with largest mass (< or =5 cm), the risk grouping was found to be an independent prognostic factor (p=0.022). However, differences in immunohistochemical staining were not related to patients' survival.
CONCLUSIONS
A risk grouping of MLC patients by using combinations of histologic parameters can be a useful tool in evaluating the survival of patients with MLCs, and may indicate clonal relationship between multiple tumors.
Value of Additional Immunocytochemical Stain for Cytokeratin in the Diagnosis of Leptomeningeal Involvement of Metastatic Carcinoma.
Junjeong Choi, Se Hoon Kim
Korean J Pathol. 2011;45(5):516-519.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.516
  • 2,449 View
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AbstractAbstract PDF
BACKGROUND
The purpose of this study was to describe potential pitfalls in the diagnosis of metastatic adenocarcinoma in cerebrospinal fluid (CSF) and to suggest additional work in association with cytokeratin immunocytochemistry for the proper diagnosis, especially in the specimens with low cellularity.
METHODS
We collected 267 cytologic specimens of CSF from patients, who were diagnosed over a 9-month period. Each of the individual samples were divided into half the sample size and processed via both, ThinPrep (TP) with Papanicolau stain and cytocentrifugation-based preparation (cytospin, CP) with immunocytochemical stain for cytokeratin.
RESULTS
Amongst the 267 cases, 45 cases from 22 patients were diagnosed to be positive for metastasis adenocarcinoma in CSF. TP with Papanicolau stain showed satisfactory cytomorphology when compared with specimen of CP preparation and cytokeratin immunocytochemical staining. All the TP processed cases belonged to satisfactory/superior categories based on the assessment of technical artifact, which potentially helps in decreasing diagnositc errors. However, in 10 out of 45 cases, diagnostic atypical cells were present only in one of the two slides.
CONCLUSIONS
Immunocytochemical stain for cytokeratin along with TP processed specimen helps in decreasing potential diagnostic errors in the cytological diagnosis of metastatic carcinoma in CSF specimen.
Case Reports
Cavernous Hemangioma of the Uterus in a Postmenopausal Woman: A Case Report.
Hye Ra Jung, Chi Hum Cho, Sang Hun Kwon, Sun Young Kwon
Korean J Pathol. 2011;45(5):520-522.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.520
  • 2,500 View
  • 15 Download
  • 2 Citations
AbstractAbstract PDF
Cavernous hemangioma of the uterus is an uncommon mesenchymal tumor. Most cases have been reported in young, pregnant women and the condition is very rare in a postmenopausal patient. An 81-year-old woman presented with a huge pelvic mass. Abdominal computed tomography and magnetic resonance imaging results suggested a leiomyoma with degenerative change and hemorrhage. Microscopically, large, thick-walled and variable-sized vascular channels were evident in the majority part of myometrium; the lining cells were immunohistochemically reactive for CD31. Vascular tumors of the female genital tract should be cautiously excised due to the profuse intra-operative bleeding. The pathological examination of a hysterectomy specimen is the only method to confirm the diagnosis of this tumor.
Ovarian Large Cell Neuroendocrine Carcinoma Associated with Endocervical-like Mucinous Borderline Tumor: A Case Report and Literature Review.
Jun Mo Kim, Hyeong Chan Shin, Mi Jin Kim
Korean J Pathol. 2011;45(5):523-528.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.523
  • 3,044 View
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  • 4 Citations
AbstractAbstract PDF
Ovarian large cell neuroendocrine carcinoma is a rare tumor that is usually associated with surface epithelial tumors. Mucinous tumors are most common surface epithelial component identified in reported cases. Ovarian mucinous tumor associated with large cell neuroendocrine carcinoma is almost always an intestinal type. However, large cell neuroendocrine carcinoma associated with pure mucinous borderline tumor of endocervical-like type has not been described previously. The present case report describes a large cell neuroendocrine carcinoma associated with endocervical-like mucinous borderline tumor of the ovary in a 35-year-old woman. The tumor was confirmed by histopathology and immunohistochemistry. A review of the pertinent literature is included.
Childhood Asymmetry Labium Majus Enlargement.
Mi Jin Gu, Sang Yoon Kim
Korean J Pathol. 2011;45(5):529-531.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.529
  • 3,208 View
  • 25 Download
  • 4 Citations
AbstractAbstract PDF
Childhood asymmetry labium majus enlargement (CALME) is a disctinctive clinicopathologic entity of pre- and early puberty first described in 2005. It is defined as an expansion of normal soft tissues of the vulva. Although CALME is not a rare lesion, it has been called lipoma, fibroma, hamartoma, and fibrous hyperplasia. CALME is not a true neoplasm and is a physiologic growth in response to hormone. It may tend to resolve spontaneously and recur after surgical resection. We report four cases of CALME with a review of the literature. To the best of the knowledge, this is the first Korean report.
Chondroblastoma of the Lumbar Spine: A Case Report and Review of the Literature.
Sun A Kim, Kyung Ja Cho, Yong Koo Park, Jong Seok Lee, Heon Ju Kwon, Hyewon Chung, Mi Jung Kim
Korean J Pathol. 2011;45(5):532-536.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.532
  • 2,772 View
  • 31 Download
  • 6 Citations
AbstractAbstract PDF
We report a case of chondroblastoma arising in the lumbar spine in a 25-year-old man who presented with low back pain of 5 years duration. Plain radiography and computed tomography revealed a well-defined osteolytic mass surrounded by marginal sclerosis in the third lumbar vertebra. The mass encroached on the left neural foramen on magnetic resonance imaging. Histologically, the tumor consisted of round to oval cells with eosinophilic cytoplasm and randomly scattered osteoclastic type giant cells. There were characteristic chicken-wire calcification and aneurysmal bone cyst-like changes. Chondroblastomas of the lumbar spine are extremely rare, and only nine cases have been reported. Spinal chondroblastoma should be distinguished from other benign bone tumors, because it tends to show aggressive biological behavior with high recurrence and mortality rates.
Mixed Endocrine-Exocrine Carcinoma of Gallbladder Derived from Dysplasia.
Min Jin Lhee, Ji Young Woo
Korean J Pathol. 2011;45(5):537-541.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.537
  • 2,250 View
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AbstractAbstract PDF
A rare case of multiple mixed endocrine-exocrine carcinoma (MEEC) of gallbladder in a 68-year-old man is described. The lesions were two separate nodules (17x13x7 mm and 17 mm in length) on the mucosa, which were composed of predominant neuroendocrine carcinoma (NEC) infiltrating into the adventitia and minor portion of adenocarcinoma (AC) or high grade dysplasia (HGD) on the surface. Surrounding mucosa showed areas of low grade dysplasia (LGD). Two nodal metastases out of 16 nodes were found containing NEC component. By immunohistochemistry, human mutL homolog 1 (hMLH1), p53, human mutS homolog 2 (hMSH2) and human mutS homolog 6 (hMSH6) showed diffuse strong positive reaction in HGD, AC and NEC, contrasting with weak positive reaction in LGD. On genetic analysis, all lesions of HGD, AC, and NEC except for LGD showed positive loss of heterozygosity in D5S346 locus. For microsatellite instability and K-ras mutation tests, all lesions showed negative results. Common immunophenotypes and molecular results among HGD, AC, and NEC suggested that NEC of this MEEC was derived from the dysplasia-AC sequence.

JPTM : Journal of Pathology and Translational Medicine