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Volume 44(4); August 2010
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Letter to the Editor
Original Articles
Expression of Minichromosome Maintenance Protein 7 and Smad 4 in Squamous Cell Carcinoma of the Esophagus.
Ji Hyun Ahn, Hee Kyung Chang
Korean J Pathol. 2010;44(4):346-353.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.346
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  • 4 Citations
AbstractAbstract PDF
BACKGROUND
Minichromosome maintenance protein 7 (MCM 7) performs a direct role in the initiation of DNA replication, which suggests that it may prove useful as a marker of cell proliferation. Smad 4 is a tumor suppressor gene that mediates the transforming growth factor beta pathway. The principal objective of this study was to characterize the expression of MCM 7 and Smad 4 and to analyze their relationship to clinicopathological parameters in patients with esophageal squamous cell carcinoma.
METHODS
Expression levels of MCM 7 and Smad 4 were evaluated via immunohistochemistry on formalin-fixed and paraffin-embedded tissues from 67 cases of esophageal squamous cell carcinoma.
RESULTS
High levels of MCM 7 expression were detected in 53 cases (74.6%), and were associated with higher T stages (p = 0.030). Kaplan-Meier survival curves demonstrated that patients with higher levels of MCM 7 expression had poorer prognoses, although this association was not significant (p = 0.086). Loss of Smad 4 expression was noted in 18 cases (23.4%), and was not associated with clinicopathological characteristics, including MCM 7 expression, or prognosis.
CONCLUSIONS
MCM 7 expression is associated with the invasiveness of esophageal squamous cell carcinoma. Altered expression of Smad 4 does not appear to have pathobiological significance in esophageal carcinoma.
Mutation and Expression of DNA2 Gene in Gastric and Colorectal Carcinomas.
Sung Hak Lee, Yoo Ri Kim, Nam Jin Yoo, Sug Hyung Lee
Korean J Pathol. 2010;44(4):354-359.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.354
  • 2,936 View
  • 18 Download
  • 3 Citations
AbstractAbstract PDF
BACKGROUND
Deregulation of DNA repair and replication are involved in cancer development. DNA2 is a nuclease/helicase that plays roles in DNA repair and replication. The aim of this study was to explore DNA2 mutation and DNA2 protein expression in gastric cancers (GCs) and colorectal cancers (CRCs).
METHODS
We analyzed two mononucleotide repeats in DNA2 in 27 GCs with high microsatellite instability (MSI-H), 34 GCs with stable MSI (MSS), 29 CRCs with MSI-H and 35 CRCs with MSS by single-strand conformation polymorphism. We also analyzed DNA2 expression in GCs and CRCs either with MSI-H or MSS.
RESULTS
We found DNA2 mutations in two GCs (7.1%) and two CRCs with MSI-H (6.9%), but not in cancers with MSS. The mutations consisted of three cases of a c.2593delT and one of a c.2592_2593delTT, which would result in premature stopping of amino acid synthesis (p.Ser865Hisfsx6 and p.Ser865Thrfsx20, respectively). DNA2 expression was observed in 16 (80%) of the GCs and 15 (75%) of the CRCs with MSI-H, but all of the cancers with DNA2 frameshift mutations were weak or negative for DNA2.
CONCLUSIONS
Our data indicate that DNA2 mutation and loss of DNA2 expression occur in GCs and CRCs, and suggest that these alterations may contribute to cancer pathogenesis by deregulating DNA repair and replication.
Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1alpha in Oral Squamous Cell Carcinomas.
Sook Hee Hong, Sang Young Roh, Yoon Ho Ko, Hye Sung Won, Myung Ah Lee, In Sook Woo, Jae Ho Byun, Jin Hyoung Kang, Young Seon Hong, Chan Kwon Jung, Yeon Sil Kim, Young Hoon Ju, Min Sik Kim
Korean J Pathol. 2010;44(4):360-369.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.360
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)-1alpha and prognosis.
METHODS
We performed immunohistochemical staining of HIF-1alpha, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection.
RESULTS
High reactivity of HIF-1alpha, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026).
CONCLUSIONS
Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1alpha may be independent prognostic factors in patients with oral SCC.
Oncocytoma and Oncocytic Carcinoma of the Salivary Glands, Single Institute Experience.
Jeong Hyeon Jo, Seung Ho Choi, Jong Lyel Roh, Soon Yuhl Nam, Sang Yoon Kim, Kyung Ja Cho
Korean J Pathol. 2010;44(4):370-375.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.370
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  • 1 Citations
AbstractAbstract PDF
BACKGROUND
Oncocytic neoplasms of the salivary glands are rare and the differential diagnosis between oncocytic carcinomas (OCs) and oncocytomas is difficult. We present 5 cases of oncocytoma and 3 cases of OC of the salivary glands with clinicopathological and immunohistochemical comparisons.
METHODS
Eight cases of oncocytic neoplasms diagnosed at Asan Medical Center between 1998 and 2009 were reviewed for clinical data and histological features. Immunohistochemical staining for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her-2), c-kit, p53, and Ki-67 was done.
RESULTS
Cytological differences between oncocytomas and OCs were not obvious, but unequivocal infiltrative growths were identified in 3 cases, rendering the diagnosis of oncocytic carcinoma. When the remaining cases were classified as oncocytomas, there was no difference in age, size, and clinical symptoms between oncocytomas and OCs. Two of 3 OCs showed strong membranous expression of c-kit, but all oncocytomas were negative. The proportion of p53-positive cells was larger in OCs than oncocytomas. Her-2 or EGFR expression was absent, and Ki-67 labeling indices were less than 1% in all cases.
CONCLUSIONS
An infiltrative growth pattern, strong membranous expression of c-kit, and an increased proportion of p53-positive cells are features that can differentiate OCs from oncocytomas of the salivary glands.
Pathologic Characteristics of Ovarian Hemorrhagic Polycyst in Estrogen Receptor-alpha (ERalpha) Knockout Mice and Roles of ERalpha in Hemorrhagic Polycyst.
Hyun Jin Son, Joo Heon Kim, Hye Kyung Lee, Mee Ja Park, Dong Wook Kang, Che Myong Ko
Korean J Pathol. 2010;44(4):376-383.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.376
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AbstractAbstract PDF
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERalphaKO) mice display several pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERalphaKO mice using a CreloxP approach and intra-ovarian ERalpha function as regulating key aspects of PCOS.
METHODS
ERalphaKO mice, which were deficient in exon 3 of the ERalpha gene, were used. Immunohistochemical studies were done on ovaries of control and ERalphaKO mice using antibodies specific to ERalpha, ERbeta, inhibin-alpha, and alpha-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B.
RESULTS
All ovaries of ERalphaKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERalphaKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of alpha-SMA.
CONCLUSIONS
ERalphaKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERalpha is the functional key to the pathogenesis of PCOS.
Expression of Carbonic Anhydrase IX Correlates with Histologic Grade and Metastasis in Osteosarcoma.
Hye Rim Park, Jinwon Seo, Patrizia Bacchini, Franco Bertoni, Yong Koo Park
Korean J Pathol. 2010;44(4):384-389.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.384
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AbstractAbstract PDF
BACKGROUND
Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients.
METHODS
We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis.
RESULTS
Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), and younger age (p = 0.0140). However, the overall survival rate was not significantly correlated with gender, tumor size, or American Joint Committee on Cancer stage.
CONCLUSIONS
CA9 expression is a frequent and tumor-specific event in osteosarcoma. CA9 expression is associated with higher grade tumors, metastasis and poor prognosis for the osteosarcoma patients.
Clinicopathological Significance of Invasive Ductal Carcinoma with High Prevalence of CD44(+)/CD24(-/low) Tumor Cells in Breast Cancer.
Ji Youn Sung, Gou Young Kim, Yong Koo Park, Juhie Lee, Youn Wha Kim, Sung Jig Lim
Korean J Pathol. 2010;44(4):390-396.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.390
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
Epithelial tumor cells with a CD44(+)/CD24(-/low) immunoprofile may have the ability to cause breast cancer. We studied these cells and their clinicopathological significance.
METHODS
The clinicopathologic findings of 100 invasive ductal carcinoma (IDC) cases and 45 ductal carcinoma in situ (DCIS) cases were reviewed. CD44(+)/CD24(-/low) tumor cells were identified by immunohistochemistry, and their clinicopathological implications in IDC and DCIS were analyzed.
RESULTS
IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells was significantly associated with larger mass, higher grade, estrogen receptor (ER) negativity, and tumor cells with a higher frequency of metastasis. The proportion of CD44(+)/CD24(-/low) tumor cells in IDC, and its DCIS components was not significantly different, whereas the proportion of CD44(+)/CD24(-/low) tumor cells was higher in DCIS than in the DCIS component of IDC (p < 0.001).
CONCLUSIONS
IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells might correlate with aggressive features, such as ER and higher grades. Moreover, the proportion of CD44(+)/CD24(-/low) tumor cells in the DCIS components of IDC and DCIS might harbor different biology, which may lead to differences in cancer progression and early carcinogenesis.
Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma.
Ji Min Jeon, Hye Won Lee, Ji Young Park, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Mi Sun Choe, Yu Na Kang, Sang Pyo Kim, Sang Sook Lee, Won Il Choi, Kun Young Kwon
Korean J Pathol. 2010;44(4):397-403.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.397
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  • 6 Citations
AbstractAbstract PDF
BACKGROUND
Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance.
METHODS
We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray.
RESULTS
We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128).
CONCLUSIONS
MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.
Growth Differentiation Factor 5 (GDF5) Core Promoter Polymorphism Is Not Associated with Susceptibility to Osteoarthritis of the Knee in the Korean Population.
Zhang Cao, Hwa Sung Lee, Jae Hwi Song, Jeong Whan Yoon, Yong Kyu Park, Suk Woo Nam, Jung Young Lee, Won Sang Park
Korean J Pathol. 2010;44(4):404-409.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.404
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  • 8 Citations
AbstractAbstract PDF
BACKGROUND
Osteoarthritis (OA) is a common disease characterized by degenerating joint cartilage in the knee, hip, and hand. A functional single nucleotide polymorphism (SNP) +104T/C; rs143383 in the 5' untranslated region of the growth differentiation factor 5 (GDF5) gene was recently associated with susceptibility to OA in the Japanese and Chinese populations.
METHODS
To investigate whether this association is present in the Korean population, the frequency of the polymorphism was investigated in 276 patients with knee OA and 298 healthy subjects as controls. Polymorphism analysis was performed by amplifying the core promoter region of the GDF5 gene and digesting it with the BsiEI restriction enzyme.
RESULTS
The frequency of the TT, CT, and CC genotypes was 54.3% (150/276), 41.7% (115/276), and 4.0% (11/276), respectively, in patients with OA, and 53.4% (159/298), 37.9% (113/298), and 8.7% (26/298), respectively, in healthy controls. No significant differences in genotypic or allelic frequencies of the +104T/C SNP of the GDF5 gene were observed between patients with OA and controls. Also, no significant differences in allelic and genotypic frequencies were found when the individuals were stratified by age and gender.
CONCLUSIONS
The results suggest that the +104T/C; rs143383 GDF5 core promoter polymorphism is not a risk factor for OA in the Korean population.
Clinical Outcome of Surgically Resected Pancreatic Intraductal Papillary Mucinous Neoplasm According to the Marginal Status: A Single Center Experience.
Sun A Kim, Eunsil Yu, Song Cheol Kim, Jihun Kim
Korean J Pathol. 2010;44(4):410-419.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.410
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  • 2 Citations
AbstractAbstract PDF
BACKGROUND
Surgical resection is the treatment of choice of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. However, the benefit of clearing resection margin is still controversial.
METHODS
We reviewed 281 surgically resected cases of IPMN. The recurrences were compared according to the histologic grade (benign or borderline IPMN, malignant noninvasive IPMN, invasive carcinoma) and size (pancreatic intraepithelial neoplasia, PanIN, less than 0.5 cm in the long axis; and IPMN, greater than or equal to 0.5 cm) of the residual lesions at the resection margin.
RESULTS
Sixty cases (21.4%) were invasive carcinoma, and 221 (78.6%) noninvasive cases included 87 (31.0%) benign, 107 (38.1%) borderline and 11 (3.9%) malignant noninvasive IPMN cases. In noninvasive IPMN, increased recurrence in patients with five or more years of follow-up was only related to the involvement of resection margin by severe dysplasia. The recurrence of invasive carcinoma was high (27.3%) even when the resection margin was clear, and was not related to the grade or size of residual tumors at the resection margin.
CONCLUSIONS
Invasiveness is a strong risk factor for recurrence in IPMN regardless of the status of the resection margin. However, in noninvasive IPMN, histologic grading of residual lesions at the resection margin predicts local recurrence.
Case Reports
Solitary Fibrous Tumor of the Kidney: A Report of Two Cases with Review of Literature.
Sun A Kim, Jung Eun Hwang, Jae Y Ro, Kyung Ja Cho, Cheryn Song, Mi Jung Kim
Korean J Pathol. 2010;44(4):420-425.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.420
  • 2,687 View
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  • 2 Citations
AbstractAbstract PDF
Solitary fibrous tumor (SFT) is a benign mesenchymal neoplasm usually occurring in the pleura. Kidney is one of the rarest sites for SFT. We report here on two cases of renal SFT found in 30-year-old and 33-year-old men with review of the literatures. Both cases manifested as well-enhanced solid masses in kidney and radical nephrectomies were done. The tumors consisted of bland-looking spindle cells arranged in short, ill-defined fascicles and storiform pattern with characteristic hemangiopericytoma-like blood vessels. The tumor cells were strongly positive for CD34 and CD99, focally positive for bcl-2, and negative for cytokeratin and human melanoma black-45 on immunohistochemical stainings. Possibility of SFT should be considered in the differential diagnosis of a renal mass which consists of benign-looking spindle cells and hemangiopericytomatous blood vessels. Immunohistochemical staining for CD34 is essential to confirm the renal solitary fibrous tumor.
Myofibrillar Myopathy: A Case Report.
Jee Young Kim, Eun Hae Jeong, Kee Duk Park, Heasoo Koo
Korean J Pathol. 2010;44(4):426-430.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.426
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AbstractAbstract PDF
Myofibrillar myopathies (MFMs) are a genetically or clinically heterogeneous group of diseases that are characterized by focal myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins. Since MFMs show morphologically distinct features but consist of genetically and clinically heterogeneous diseases, muscle biopsy is important for the diagnosis. A 20-year-old man complained of progressive weakness and atrophy of both legs for two years. He had a dysmorphic face and short stature. The light microscopic examination of his muscle biopsy showed mixed myopathic and neurogenic changes. Many myofibers with multiple clusters of blue red rod-like structures and cytoplasmic inclusions were noted. Immunohistochemistry showed a focal positive reaction in sarcoplasm to desmin and myotilin antibodies. An electron microscope study revealed variable abnormalities of myofibrillar structures. To the best of our knowledge, this is the first reported case of MFM with pathology findings in Korea.
Exuberant Smooth Muscle Cells in Fibroadenoma of the Breast: A Case Report.
Ga Eon Kim, Young Kim, Eun Hui Jeong, Jo Heon Kim, Min Ho Park, Ji Shin Lee
Korean J Pathol. 2010;44(4):431-434.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.431
  • 3,390 View
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  • 1 Citations
AbstractAbstract PDF
Smooth muscle cell metaplasia is an extremely rare form of stromal differentiation in fibroadenomas. We describe a case of fibroadenoma with exuberant smooth muscle cells in a 72-year-old woman. The mass was located in the upper central portion of the left breast. It was well circumscribed and its greatest dimension was 3 cm. Histologically, the glandular elements resembled the appearance of fibroadenoma, but the stromal elements were composed of spindle cell bundles with abundant eosinophilic cytoplasm and elongated cigar-shaped nuclei. Neither mitotic activity nor cellular atypia was seen. The stromal cells were immunohistochemically positive for smooth muscle actin, calponin, desmin, and estrogen receptor-beta, but negative for CD34, S-100 protein, p63, CD10, estrogen receptor-alpha, progesterone receptor and cytokeratin. These results proved that the stromal cells showed features of smooth muscle cells.
First Report of a Gangliocytic Paraganglioma Arising in a Tailgut Cyst.
Yosep Chong, Mee Yon Cho
Korean J Pathol. 2010;44(4):435-440.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.435
  • 2,798 View
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  • 1 Citations
AbstractAbstract PDF
Here we present the first report of a gangliocytic paraganglioma arising in a tailgut cyst; it occurred in a 56-year-old man. Tailgut cysts are uncommon congenital hamartomatous lesions that arise in the retrorectal presacral space in infants or adults. Benign or malignant tumors associated with tailgut cysts are rarely described; the most common tumors are adenocarcinomas and carcinoid tumors. A gangliocytic paraganglioma is a rare benign tumor that occurs nearly exclusively in the second portion of the duodenum. Rare cases have been reported at other locations, but a tailgut cyst has never been described. In our case, a resected 3.9 x 3.3 x 3 cm mass was composed predominantly of a solid yellow white neuroendocrine tumor within the area of a tailgut cyst. The neuroendocrine component of this tumor was different from previously described carcinoid tumors with respect to the histologic findings of neural differentiation as well as the intermixed typical gangliocytic features highlighted by immunohistochemical stains for S-100 protein and neurofilament. Although an intermixed area of the tailgut cyst and gangliocytic paraganglioma were found in some areas, the pathogenesis of this tumor remains to be elucidated.

JPTM : Journal of Pathology and Translational Medicine