Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence

BACKGROUND: Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients. METHODS: HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining. RESULTS: The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1-2 HCC subgroup (median, 126 months vs. 35 months; p = .015). CONCLUSIONS: Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.

Low-Grade Fibromyxoid Sarcoma of the Malar Area

No abstract available.

Loss of FAT Atypical Cadherin 4 Expression Is Associated with High Pathologic T Stage in Radically Resected Gastric Cancer

PURPOSE: Recent studies have revealed recurrent alterations in the cell adhesion gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4 (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which is involved in the control of organ size. Here, we investigated the loss of FAT4 expression and its association with clinicopathological risk factors in gastric cancer. MATERIALS AND METHODS: We assessed the expression of FAT4 by using immunohistochemistry on three tissue microarrays containing samples from 136 gastric cancer cases, radically resected in the Soonchunhyang University Cheonan Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4 was semi-quantitatively scored using the H-score system. An H-score of > or =10 was considered positive for FAT4 expression. RESULTS: Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score or =10, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score or =10, mean survival 62.7+/-7.3 months vs. 79.1+/-3.1 months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival. CONCLUSIONS: Loss of FAT4 expression appears to be associated with invasiveness in gastric cancer.

Loss of ARID1A Expression in Gastric Cancer: Correlation with Mismatch Repair Deficiency and Clinicopathologic Features

PURPOSE: The AT-rich interactive domain 1A (ARID1A) gene encodes BRG1-associated factor 250a, a component of the SWItch/Sucrose NonFermentable chromatin remodeling complex, which is considered a tumor suppressor in many tumors. We aimed to investigate the prognostic significance of ARID1A expression in gastric cancers and explore its relationship with clinicopathologic parameters such as mismatch repair protein expression. MATERIALS AND METHODS: Four tissue microarrays were constructed from 191 resected specimens obtained at Soonchunhyang University Cheonan Hospital from 2006 to 2008. Nuclear expression of ARID1A was semiquantitatively assessed and binarized into retained and lost expression. RESULTS: Loss of ARID1A expression was observed in 62 cases (32.5%). This was associated with more frequent vascular invasion (P=0.019) and location in the upper third of the stomach (P=0.001), and trended toward more poorly differentiated subtypes (P=0.054). ARID1A loss was significantly associated with the mismatch repair-deficient phenotype (P=0.003). ARID1A loss showed a statistically significant correlation with loss of MLH1 (P=0.001) but not MSH2 expression (P=1.000). Kaplan-Meier survival analysis showed no statistically significant difference in overall survival; however, patients with retained ARID1A expression tended to have better overall survival than those with loss of ARID1A expression (P=0.053). In both mismatch repair-deficient and mismatch repair-proficient groups, survival analysis showed no differences related to ARID1A expression status. CONCLUSIONS: Our results demonstrated that loss of ARID1A expression is closely associated with the mismatch repair-deficient phenotype, especially in sporadic microsatellite instability-high gastric cancers.

A Rare Case of Primary Tubular Adenocarcinoma of the Thymus, Enteric Immunophenotype: A Case Study and Review of the Literature

Thymic carcinomas are uncommon malignant tumors, and thymic adenocarcinomas are extremely rare. Here, we describe a case of primary thymic adenocarcinoma in a 59-year-old woman. Histological examination of the tumor revealed tubular morphology with expression of cytokeratin 20 and caudal-type homeobox 2 according to immunohistochemistry, suggesting enteric features. Extensive clinical and radiological studies excluded the possibility of an extrathymic primary tumor. A review of the literature revealed only two global cases of primary tubular adenocarcinomas of the thymus with enteric immunophenotype.

Loss of Tumor Suppressor ARID1A Protein Expression Correlates with Poor Prognosis in Patients with Primary Breast Cancer / 한국유방암학회지

PURPOSE: Somatic mutations of the chromatin remodeling AT-rich interactive domain 1A (SWI-like) gene (ARID1A) have been identified in many human cancers, including breast cancer. The purpose of this study was to evaluate the nuclear expression of ARID1A in breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance. METHODS: IHC was performed on tissue microarrays of 476 cases of breast cancer. Associations between ARID1A expression and clinicopathologic characteristics and molecular subtype were retrospectively analyzed. RESULTS: Low expression of ARID1A was found in 339 of 476 (71.2%) cases. Low expression of ARID1A significantly correlated with positive lymph node metastasis (p=0.027), advanced pathologic stage (p=0.001), low Ki-67 labeling index (p=0.003), and negative p53 expression (p=0.017). The ARID1A low expression group had significantly shorter disease-free and overall survival than the ARID1A high expression group (p<0.001 and p<0.001, respectively). Multivariate analysis demonstrated that low expression of ARID1A was a significant independent predictive factor for poor disease-free and overall survival in patients with breast cancer (disease-free survival: hazard ratio, 0.38, 95% confidence interval [CI], 0.20-0.73, p=0.004; overall survival: hazard ratio, 0.11, 95% CI, 0.03-0.46, p=0.003). In patients with luminal A type disease, patients with low ARID1A expression had significantly shorter disease-free and overall survival rates than patients with high ARID1A expression (p=0.022 and p=0.018, respectively). CONCLUSION: Low expression of ARID1A is an independent prognostic factor for disease-free and overall survival in breast cancer patients and may be associated with luminal A type disease. Although the biologic function of ARID1A in breast cancer remains unknown, low expression of ARID1A can provide valuable prognostic information.

Mediastinal Glomus Tumor: A Case Report and Literature Review

A glomus tumor in the mediastinum is very uncommon, and only five cases have been reported in the English literature. We recently encountered a 21-year-old woman with an asymptomatic mediastinal mass that measured 5.3 x 4.0 cm. Surgical excision was performed, and the tumor was finally diagnosed as mediastinal glomus tumor with an uncertain malignant potential. After reviewing this case and previous reports, we analyzed the clinicopathologic features associated with progression of such a tumor.

Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

BACKGROUND: The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines. METHODS: Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines. RESULTS: Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity. CONCLUSIONS: This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.

The Histologic Cut-off Point for Adjacent and Remote Non-neoplastic Liver Parenchyma of Hepatocellular Carcinoma in Chronic Hepatitis B Patients

BACKGROUND: The molecular profile of peritumoral non-neoplastic liver parenchyma (PNLP) has recently been suggested as predictive factor of early and late recurrence of hepatocellular carcinoma (HCC). However, there is no definite cut-off point for tumor-free PNLP in terms of either histological or molecular changes. Therefore, our aim is to determine the numerical cut-off point for separating adjacent PNLP and remote PNLP in histopathologic perspective. METHODS: Peritumoral tissues from 20 resected HCC patients were sampled from 0 to 40 mm distance from the tumor border (divided into 5-mm columns). Histopathologic parameters such as necroinflammatory activity, fibrosis, bile ductular reaction, hepatic venulitis, peliosis, and steatosis were compared between each column. RESULTS: The morphologic changes just adjacent to the tumor were notably severe and faded with distance. The parenchyma within 10 mm of the tumor showed significantly severe inflammation, fibrosis, peliosis and hepatic venulitis compared with those from farther areas. The histopathologic changes of the parenchyma became stable beyond 20 mm. CONCLUSIONS: Results of this study revealed that the parenchyma within 10 mm distance from the tumor, or adjacent PNLP, has histopathologic changes that are directly affected by the tumor, and the parenchyma beyond 20 mm as the remote PNLP without tumor effect.