Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas.

BACKGROUND: Recent studies have revealed that the splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in fibroblasts and accumulated T cells of tertiary lymphoid structures. In the present study, we investigated NOVA1 expression in various subtypes of mature and immature T- and natural killer (NK)-cell lymphomas as well as in various B-cell lymphoma subtypes. METHODS: NOVA1 immunoexpression was evaluated in hyperplastic palatine tonsils (n = 20), T- and NK-cell lymphomas (n = 177), diffuse large B-cell lymphomas (n = 151), and other types of B cell lymphomas (n = 31). Nuclear staining intensity and percentage of positive tumor cells were graded. NOVA1 mRNA expression was analyzed in various lymphoma cell lines. RESULTS: Tumor cells of T- and NK-cell lymphomas showed higher expression levels of NOVA1 than did normal paracortical T cells, and 56.5% of T- and NK-cell lymphoma cases showed diffuse and strong expression. The NOVA1 expression level varied according to the subtype; it was higher in angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), and T lymphoblastic leukemia/lymphoma (T-LBL), but it was lower in ALK-positive ALCL. In almost all B-cell lymphomas, NOVA1 expression was very low or negative. NOVA1 mRNA was also expressed in Jurkat, a T-LBL cell line. CONCLUSIONS: The present findings suggest that NOVA1 upregulation may be involved in certain subtypes of T- and NK-cell lymphomas, but not in B-cell lymphomas. Upregulated NOVA1 expression seems to be a specific biological feature of activated T cells such as T- and NK-cell lymphomas.ope

Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection

PURPOSE: The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status. MATERIALS AND METHODS: Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed. RESULTS: In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed. CONCLUSION: It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.ope

Clinicopathological and immunohistochemical characterization of papillary proliferation of the endometrium: A single institutional experience.

Papillary proliferation of the endometrium is an unusual lesion that is composed of papillae with fibrovascular stromal cores covered with benign-appearing glandular epithelium. We studied the clinicopathological and immunohistochemical features of four cases of endometrial papillary proliferations. All patients were postmenopausal. Two lesions were incidental findings in hysterectomy specimens, and two lesions were detected in endometrial curettage specimens. Based on the degree of architectural complexity and extent of proliferation, we classified papillary proliferations histopathologically into "simple" or "complex" growth patterns. Three cases were classified as simple papillary proliferation, and one case was classified as complex papillary proliferation. Simple papillary proliferations were characterized by slender papillae with delicate stromal cores. In contrast, complex papillary proliferations had intracystic papillary projections and cellular clusters with frequent branching and occasional cytological atypia. All cases showed coexistent metaplastic epithelial changes, including mucinous metaplasia, eosinophilic cell change, and ciliated cell metaplasia. One patient with simple papillary proliferations had coexistent well-differentiated endometrioid carcinoma. One patient had subsequent hyperplasia without atypia, and another patient had subsequent atypical hyperplasia/endometrioid intraepithelial neoplasia; both patients underwent total hysterectomy within four months. Our observations are consistent with previous data demonstrating that endometrial papillary proliferations coexist with or develop into atypical hyperplasia/endometrioid intraepithelial neoplasia or endometrioid carcinoma. It is very important for pathologists to discriminate papillary proliferations from neoplastic lesions (including atypical hyperplasia/endometrioid intraepithelial neoplasia and well-differentiated endometrioid carcinoma) and benign mimickers (including papillary syncytial metaplasia).ope

Alteration status and prognostic value of MET in head and neck squamous cell carcinoma

The MET pathway plays a key role in various cancers, and its inhibition represents a potential treatment target. However, appropriate biomarkers are needed to facilitate the selection of patients who would benefit from MET inhibiting therapy. We herein conducted a robust confirmatory evaluation of the MET copy number alteration status and prognostic significance of c-Met expression in a large series of patients (n = 396) who underwent standard surgical resection and adjuvant chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC). Surgically resected HNSCC samples were subjected to immunohistochemical and H-score analysis of c-Met expression and silver in situ hybridization analysis of MET amplification and copy number gains. c-Met expression varied, with mean and median H-scores (scale: 0-300 scale) of 61.2 and 60.0, respectively. The lowest and highest expression levels were observed in SCC of the larynx and oral cavity, respectively. MET copy number gains were observed in 16.9% of cases (67/339) and were associated with c-Met protein expression. High c-Met expression, determined according to MET gain status, was associated with an inferior overall survival rate, especially among completely resected cases. In conclusion, our robust analysis revealed that c-Met expression in HNSCCs varied according to anatomical site, correlated with MET copy number gains, and was associated with poor prognosis. This c-Met expression analysis method, which is based on the MET gain status, appears to appropriately predict high-risk HNSCC patients in the context of anti-MET therapeutic decisions.ope

The prognostic significance of monoclonal immunoglobulin gene rearrangement in conjunction with histologic B-cell aggregates in the bone marrow of patients with diffuse large B-cell lymphoma.

Bone marrow involvement (BMI) is a well-known poor prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL). This study robustly investigated the significance of monoclonal immunoglobulin gene rearrangement combined with histologic B-cell aggregates in bone marrow (BM) in the detection of a poor prognostic group. Pretreatment BM samples of 394 DLBCL patients were analyzed via the immunoglobulin gene rearrangement study and the microscopic examination. Monoclonal immunoglobulin gene rearrangement was detected in 25.4% of cases. Histologic B-cell aggregates with the features of large B-cell lymphoma aggregates, small cell B-cell lymphoma aggregates, or B-cell aggregates of unknown biological potential were observed in 12% of cases (6.9%, 1.3%, and 3.8%, respectively). Histologic B-cell aggregates were more associated with monoclonality than polyclonality. Cases with both monoclonality and histologic B-cell aggregates demonstrated close association with poor prognostic factors such as a higher International Prognostic Index score and showed an inferior overall survival rate when compared to cases with only monoclonality or only histologic B-cell aggregates. From the findings, a combination of monoclonality and histologic B-cell aggregates within the bone marrow was highly associated with poor prognosis and could be used to determine high-risk DLBLC patients with greater sensitivity and specificity than conventional microscopic examination or immunoglobulin gene rearrangement study alone.ope

Analysis of Korean intra-industry FDI and its relationship with intra-industry Trade

Thesis(master`s)--서울대학교 國際大學院 :國際學科, 國際通商專攻,2006.Maste

공익광고에서 공격적 메시지의 효과에 관한 연구

학위논문(석사)--서울대학교 대학원 :신문학과,1996.Maste

Malignant lymphoma arising in cardiac myxoma, presenting with peripheral arterial emboli

Composite tumors of cardiac myxoma and malignant lymphoma are extremely rare, with 11 of such cases reported in the literature. A 44-year-old man presented to us with abrupt right lower leg pain. A computed tomography angiogram revealed segmental obstruction of the right common femoral artery, and embolectomy was performed. The embolectomy specimen contained several clusters of degenerated round/oval atypical cells in the fibrinous or myxoid background. Immunohistochemical examination revealed that these atypical cells were negative for cytokeratin and non-specifically expressed CD45. After one year of follow-up, the patient presented with dyspnea on exertion. Transthoracic echocardiography revealed a 5.7x1.9 cm, lobulated, echogenic, intracardiac mass, and excision was performed. Microscopically, most of the mass was composed of stellate or curved cells with eosinophilic cytoplasm in the myxoid background. However, several clusters or scattered round/oval atypical cells, similar to those observed in the embolectomy specimen, were observed. These atypical cells were positive for CD45 and CD20, with a Ki-67 labeling index of 90%. Calretinin was expressed in stellate cells but not in atypical cells. Therefore, we made a diagnosis of diffuse large B cell lymphoma (DLBCL) arising in the cardiac myxoma. Our case is an extremely rare example of a composite tumor of cardiac myxoma and DLBCL presenting with peripheral arterial emboli. Thorough histological evaluation of embolectomy and cardiac myxoma specimen is crucial for the diagnosis of composite tumor.restrictio