BACKGROUND JC virus (JCV) is a polyomavirus that commonly infects humans and can cause progressive multifocal leukoencephalopathy in immunocompromised patients. Recently, many reports have documented detection of JCV in gastrointestinal tract cancers. We investigated the presence of JCV in gastric adenocarcinoma, adenoma, and non-neoplastic gastric mucosa. METHODS We selected paraffin-embedded tissue from endoscopic mucosal resections performed from January 2007 to September 2008. DNA was extracted from the paraffin-embedded specimens of 30 adenocarcinomas, 20 adenomas of the stomach, and 20 non-neoplastic gastric mucosa. Polymerase chain reaction amplifications were performed using gene-specific primers to detect the JCV gene sequences, and immunohistochemical staining was performed to detect the T-antigen (T-Ag) protein. RESULTS The T-Ag sequence was detected in nine of 30 gastric cancers (30%), two of 20 adenomas (10%), and eight of 20 non-neoplastic gastric mucosa specimens (40%). T-Ag protein expression was found in five of 30 gastric cancers (16.7%) and one of 20 non-neoplastic gastric mucosa specimens (5%), whereas no expression was observed in any of the adenomas. CONCLUSIONS Although we could not detect a correlation between JCV and gastric cancer, we demonstrated the presence of JCV T-Ag expression in human gastric cancers. These findings suggest a possible role for JCV in gastric carcinogenesis.
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BACKGROUND Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement. METHODS Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry. RESULTS OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls. CONCLUSIONS The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.
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Podocyte Expression of Osteopontin and FSP-1/S100A4 in Human Crescentic Glomerulonephritis Ghil Suk Yoon, Tae Sook Kim The Korean Journal of Pathology.2011; 45(3): 237. CrossRef
BACKGROUND The epithelial mesenchymal transition (EMT) is intimately associated with tumor hypoxia. The present study was conducted to investigate the immunohistochemical relationship between hypoxic and EMT-related molecules in non-small cell lung carcinoma (NSCLC). METHODS Immunohistochemical staining for hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase (CA) IX, TWIST, and E-cadherin proteins was performed in 146 cases of NSCLC (80 cases of adenocarcinoma and 66 cases of squamous cell carcinoma) using tissue microarray blocks. RESULTS HIF-1alpha, TWIST, CA IX, and E-cadherin were expressed in 58 (40%), 90 (62%), 82 (56%), and 36 (25%) of 146 NSCLC cases, respectively. TWIST expression was positively correlated with HIF-1alpha expression (p = 0.03) and inversely correlated with E-cadherin expression (p < 0.01). TWIST and CA IX expression were not significantly interrelated, but each showed a relationship with histological tumor grade. However, the expression of these molecules had no significant effect on clinical staging or patient survival. CONCLUSIONS Although TWIST expression was correlated positively with HIF-1alpha expression and inversely correlated with E-cadherin, HIF-1alpha expression was not associated with E-cadherin expression. However, considering the relationship between HIF-1alpha and TWIST expression, further studies should be performed to demonstrate the role of hypoxia-induced EMT in NSCLC.
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BACKGROUND S100A4 has been implicated in invasion and metastasis of various malignant tumors. The aim of this study was to investigate whether or not S100A4 plays an important role in non-small cell lung carcinomas (NSCLCs). METHODS Sixty-seven patients with NSCLC including 37 with squamous cell carcinomas (SCCs) and 30 with adenocarcinomas (ADs) who had undergone surgical resection were analyzed.
S100A4 expression was analyzed by immunohistochemistry using tissue microarray blocks. RESULTS S100A4 expression was positive in 56 (83.6%) of 67 NSCLC cases. ADs were more frequently S100A4 positive than SCCs (p = 0.017). However, no significant correlation was observed between S100A4 expression and age, gender, pT, pN or tumor, node and metastasis (TNM) stage. Two distant metastatic cases revealed an S100A4 positive reaction.
Kaplan-Meier survival curves with the log-rank test showed no correlation with 3-year survival (p = 0.782) or 5-year survival (p = 0.227) in either group of patients according to S100A4 expression. CONCLUSIONS S100A4 expression was not correlated with age, gender, pT, pN or TNM stage or survival in patients with NSCLCs. Therefore, S100A4 expression may not be useful as a prognostic marker for NSCLCs. However, S100A4 expression showed a higher positivity in ADs than in SCCs.
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BACKGROUND Smoking and alcohol consumption are the main risk factors for squamous cell carcinoma of the upper aerodigestive tract (SCCUAT). However, human papillomavirus (HPV) has been etiologically linked with tonsillar squamous cell carcinoma (TSCC). Therefore, we investigated the etiologic role of HPV in the context of SCCUAT in Korea. METHODS Archival paraffin block samples from 136 cases previously diagnosed as SCCUAT were randomly selected. A commercial HPV DNA chip was used for HPV genotyping. RESULTS One hundred and seventeen cases were available after checking beta-globin (47 cases of tonsil and 70 of non-tonsil). A HPV-positive result (HPV 16 and 18) occurred in 13 cases of SCCUAT, and 12 cases were tonsil (25.5%, 12/47). Among the 12 HPV-positive patients with TSCC, nine were non-smokers and non-drinkers. Most HPV-negative patients with TSCC had a history of alcohol drinking and smoking (32/35, 91.4%). HPV infection status was not significantly associated with histological grade, clinical stage, or survival in patients with TSCC. CONCLUSIONS HPV infection was significantly higher in patients with TSCC among those with SCCUAT. HPV may be independent risk factor in development of TSCC, such as smoking and alcohol drinking.
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BACKGROUND The Scribble, Par and Crumbs polarity modules are essential for establishing and maintaining apicobasal cell polarity in epithelial cells. The aim of the present study was to investigate the expression pattern of Lethal giant larvae2 (Lgl2) in normal colonic epithelium and epithelial tumors and to examine the relationship between Lgl2 expression and clinicopathological parameters. METHODS We examined Lgl2 expression in 66 primary colon cancers and 20 adenomas by immunohistochemistry. RESULTS In normal colonic epithelium, Lgl2 was strongly expressed at the basolateral membrane of cells in the luminal surface but was not expressed at the base of crypts.
The expression pattern of E-cadherin in normal epithelium was similar to that of Lgl2. In contrast, tumors did not express Lgl2 or showed diffuse cytoplasmic staining. The Lgl2 positive rate in tumors was significantly lower than in normal epithelium, and its negative rate in tumors was higher in tumors with abnormal E-cadherin expression than in tumors with positive membranous staining. Lgl2 staining intensity was significantly lower in tumor budding sites than in tumor centers. No significant differences were observed between Lgl2 and clinicopathological parameters. CONCLUSIONS Lgl2 expression was reduced or localized at the cytoplasm in colon epithelial tumors, suggesting that a perturbation of Lgl2 expression frequently occurs in colon epithelial tumors.
BACKGROUND Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas. METHODS Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2. RESULTS IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%. CONCLUSIONS HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas.
Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas.
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Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung-Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S Journal of Gastric Cancer.2014; 14(2): 87. CrossRef
BACKGROUND Primary splenic vascular lesions include the tumor and the inflammatory condition. A primary splenic vascular tumor is rare but is the most common tumor of the benign primary splenic tumors. METHODS We describe the clinicopathological, radiological, and immunophenotypical findings of 40 cases of primary vascular lesions identified at our hospital from 1996 to 2009. RESULTS The patients included 18 men and 22 women, aged 12 to 74 years, with a mean of 43.3-years and median of 40-years. They comprised 14 hemangiomas (35%), 13 lymphangiomas (32.5%), three hamartomas (7.5%), three littoral cell angiomas (7.5%), three sclerosing angiomatoid nodular transformations (SANT, 7.5%) and four angiosarcomas (10%). The majority of the patients (65%) were asymptomatic.
Some of the patients (32.5%) complained of abdominal pain, and 2.5% of the patients presented with fever. Metastases were identified in 75% of the patients with an angiosarcoma at the initial work-up. One angiosarcoma patient died of the disease despite adjuvant chemoradiotherapy. The radiological findings for hamartoma, littoral cell angioma, and SANT were nonspecific. Microscopically, six types of vascular lesions showed classic morphological and immunophenotypical features of their type. CONCLUSIONS One should be aware of rare splenic vascular lesions when radiological findings are nonspecific.
Histomorphological and immunophenotypical features are helpful for the differential diagnosis.
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BACKGROUND Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer. METHODS The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16(INK4a), p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers. RESULTS High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors. CONCLUSIONS Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.
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BACKGROUND The Bethesda classification system for reporting on thyroid fine-needle aspiration (FNA) cytology was recently proposed by the National Cancer Institute, USA. We aimed to report our experience with applying this system for thyroid FNA, with a focus on comparing it with the four categorical system. METHODS We retrospectively reviewed the 4,966 thyroid FNAs that were performed at the Seoul St. Mary's Hospital between October 2008 and September 2009. All the FNAs were classified according to the Bethesda system and the four tier system. RESULTS The cytologic diagnoses of the Bethesda system included 10.0% unsatisfactory, 67.7% benign, 3.1% atypia of undetermined significance, 0.6% follicular neoplasm, 0.5% follicular neoplasm, Hurthle cell type, 5.1% suspicious for malignancy and 13.0% malignancy. Using four tier system, 10.1%, 67.6%, 9.3%, and 13% were diagnosed as unsatisfactory, negative for malignancy, atypical cells and malignancy, respectively. Of the 4,966 nodules, 905 were histologically confirmed. The specificity of the Bethesda system and the four tier system for diagnosing malignancy was 99.6% and 82.6%, respectively. CONCLUSIONS The Bethesda system can classify indeterminate thyroid nodules into more detailed categories and provide clinicians with useful information for management.
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BACKGROUND We examined cervicovaginal smears that contained definite low-grade squamous intraepithelial lesion (LSIL) cells and rare atypical cells suggestive of high-grade SIL (HSIL) (ASC-H) or contained borderline dysplastic cells between LSIL and HSIL. Such lesions were classified as LSIL-H. This study aimed to investigate the cytologic and histologic characteristics of LSIL-H category and we evaluated the associated clinical risk. METHODS The histologic outcomes of LSIL-H were compared with those of LSIL and ASC-H. Both the cytologic and histologic findings of LSIL-H that were confirmed as cervical intraepithelial neoplasia 2 (CIN2) or greater (CIN2+) were investigated. RESULTS LSIL-H accounted for 0.09% of the Pap tests. On the follow-up histology, the most frequent outcome was CIN2, and the risk of CIN2+ was higher than that for ASC-H. In the cases of LSIL-H that was histologically confirmed as CIN2+, most of the atypical cells suggestive of HSIL were cytologically similar to those of CIN2, and the corresponding cervical tissues were characterized by small CIN2+ lesions in a large background of flat condyloma/CIN1.
The LSIL-H cases not confirmed on initial colposcopically-directed biopsy required further follow-up. CONCLUSIONS LSIL-H may be a valid diagnostic category with distinctive features that are different from LSIL or ASC-H.
LSIL-H needs further follow-up for the proper management.
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Solitary fibrous tumor is an uncommon neoplasm of mesenchymal origin that primarily affects the pleura. This tumor has been rarely found in liver parenchyma. We present an additional case of a solitary fibrous tumor in the liver of a 46-year-old woman. A contrast-enhanced magnetic resonance image revealed a well-defined round hepatic mass with strong homogeneous enhancement on arterial phase imaging. The tumor was composed of cytologically bland spindle cells with alternating hypercellular and hypocellular sclerotic areas. Immunohistochemistry indicated that the tumor cells were positive for vimentin, CD34, CD99 and smooth muscle actin, but negative for cytokeratin, human melanoma black 45, CD117, bcl-2, and S-100 protein.
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Herein we report a rare case of mucinous bronchioloalveolar carcinoma (BAC) associated with a solitary bronchiectatic cyst in a 29-year-old man. The patient presented with hemoptysis and had a history of pulmonary tuberculosis.
Chest radiographs and computed tomography revealed a well-circumscribed, thin-walled cavitary lesion in the right upper pulmonary lobe. Gross examination of a lobectomy specimen showed a bronchiectatic cavity and a fungus ball within it. There were also several ill-defined small gray-white nodules around the cyst, nodules that were mucinous BAC. On microscopy, they were composed of columnar tumor cells along the intact alveolar walls in a single layer.
Jugulotympanic paragangliomas (JTPs) known as glomus tumors, are neoplasms of variable invasiveness that arise from the paraganglia situated around the jugular bulb or middle ear.
We now report a rare case of JTP in an 18-year-old male.
Preoperative diagnoses through external auditory canal biopsy and radiologic examination both failed. Even using a frozen section, an informative finding was not obtained because mostly granulation tissue was present along with associated squeezing artifacts. On permanent histologic examination, small cell nests between many ectatic small vessels and fibrotic stroma were seen, and those cells were positive for CD56, synaptophysin and chromogranin. Because JTPs are rare and have rather different histologic findings - higher vascularity, smaller and less uniform tumor cells than other paragangliomas - they are easy to misdiagnose.
However, remembering those differences may help the physician avoid missing JTPs.