Woo Ick Yang

Angiocentric Lymphoma of the Head and Neck: Patterns of Systemic Failure After Radiation Treatment

PURPOSE To investigate the patterns of systemic failure and the clinical outcome in patients with angiocentric lymphoma of the head and neck who were treated with radiation alone, and to discuss the optimal mode of treatment for these patients. PATIENTS AND METHODS We reviewed the records of 92 patients with stage I or II angiocentric lymphoma who were treated at Yonsei Cancer Center between 1976 and 1994. All patients were treated with involved-field irradiation. Radiation doses ranged from 40 to 60 Gy (median dose, 50.4 Gy). Treatment response, patterns of treatment failure including systemic failure, and clinical outcome after radiation treatment were analyzed. RESULTS The most frequently involved site was the nasal cavity, either alone or in conjunction with other sites. In 16 patients (17.4%), angiocentric lymphoma was accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). After completion of radiation treatment, 61 patients (66.3%) achieved a complete response and 16 (17.4%) a partial response. Half of the patients (50.0%) ultimately experienced local recurrence with or without other components of failure, whereas regional failure was relatively uncommon (10.9%). Systemic failure occurred in 25.0% of patients during follow-up. Six patients had histologic findings identical to those at the time of the original disease (group I), whereas four patients exhibited morphologic features of frank lymphomas (group II). The majority of patients with systemic relapse had the predilection sites for widespread extranodal involvement, such as the skin, brain, lung, gastrointestinal tract, or testes. In addition, seven patients died from various medical illnesses or immunologic disorders, including hemophagocytic syndrome and second primary cancers (group III). After a median follow-up of 56 months, the overall survival and disease-free survival rates for all patients were 40.1% and 37.8%, respectively. All patients except one with systemic failure died within 1 year. CONCLUSION Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.

Protein kinase CK2α as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia

Introduction: Protein kinase CK2 is implicated in cellular proliferation and transformation. However, the clinical and biological significances of CK2 have not been elucidated in acute myeloid leukemia (AML). Experimental Design: We evaluated the biological significances of catalytic subunit of CK2 (CK2α) expression in leukemia cell lines and primary leukemic blasts obtained from AML patients. Results: In this study, the expression of CK2α was elevated in a substantial proportion of AML. In AML patients with normal karyotype, the disease-free survival and overall survival rates were significantly lower in the CK2α-high compared with the CK2α-low AML cases (P = 0.0252 and P = 0.0392, respectively). An induced overexpression of CK2α increased the levels of Ser473 phosphorylated (p)-Akt/protein kinase B (PKB), p-PDK1, pFKHR, p-BAD, Bcl-2, Bcl-xL, Mcl-1, and XIAP. Treatment of U937 cell line and primary AML blasts with selective CK2 inhibitor, tetrabromobenzotriazole or apigenin, reduced the levels of these molecules in a dose-dependent manner. CK2α small interfering RNA treatment also resulted in a down-regulation of p-Akt/PKB and Bcl-2 in U937 cells. Apigenin-induced cell death was preferentially observed in the CK2α-high leukemia cell lines, HL-60 and NB4, which was accompanied by cytoplasmic release of SMAC/DIABLO and proteolytic cleavage of procaspase-9, procaspase-3, procaspase-8, and poly(ADP)ribose polymerase. An induced overexpression of CK2α potentially enhanced the sensitivity of U937 cells to the apigenin-induced cell death. Apigenin-induced cell death was significantly higher in CK2α-high AML compared with CK2α-low AML (P < 0.0001) or normal bone marrow samples (P < 0.0001). Conclusion: These findings strongly suggest protein kinase CK2α as an unfavorable prognostic marker and novel therapeutic target in AML.

Alveolar soft part sarcoma: MR and angiographic findings

Abstract Objective. To present the MR and angiographic findings of alveolar soft part sarcoma (ASPS). Design and patients. MR examinations (12 tumors of 10 patients) of ASPS performed at multiple hospitals were retrospectively reviewed. The tumors were found in the thigh (n=4), lower leg (n=4), femur (n=2, local metastasis), scalp (n=1) and arm (n=1). The MR signal characteristics including signal intensity, homogeneity and signal void of lesions and bony invasion including direct invasion or local metastasis were evaluated. Angiographic findings (n=4) and post-embolotherapy follow-up MR imaging (n=2) findings were also assessed. Results. Local bony metastasis was found in two cases. Seven tumors showed heterogeneous high signal intensity on T1- and T2-weighted images with good enhancement. One tumor had a very high signal on T1-weighted images. Eight tumors (67%) showed numerous signal voids in or near the tumors. All four angiographic studies showed numerous enlarged vessels, arteriovenous shunts and delayed washout. Two cases mimicked arteriovenous malformations on angiographic studies but MR images demonstrated solid soft tissue components as well as tortuous vessels. Conclusions. High signal on T1-weighted image and numerous signal voids are highly suggestive of ASPS, although they are not universal as has been suggested and arteriovenous malformation should be included in the differential diagnosis. Local bony metastases in ASPS were seen in two cases and should be carefully investigated.

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography

Purpose18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high 18F-FDG uptake have more aggressive biological potential than those with low uptake.MethodsSurgical specimens were obtained from ten patients with HCC (six males and four females, age range 38–68 years). The tumour samples were divided into two groups based on the 18F-FDG PET scan findings: high 18F-FDG uptake (n=4) and low 18F-FDG uptake (n=6).ResultsThe pathological tumour grade was closely correlated with the 18F-FDG uptake pattern: HCCs with high 18F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high 18F-FDG uptake showed increased expression of 11 genes—including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose:N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor—compared to those with low uptake (p<0.005). Nine genes, including regulator of mitotic spindle assembly 1, grb2-related adaptor protein and beta-1,3-n-acetylglucosaminyltransferase, were repressed.ConclusionGene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high 18F-FDG uptake appear to have more aggressive biological properties than those with low uptake.

Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysis

The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas.

Expression of estrogen receptor-β in normal mammary and tumor tissues: Is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-β (ERβ) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERβ in BC development and progression. ERβ expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERβ mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERβ mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERβ expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERβ expression. Collectively, ERβ mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.

Expression of cyclin E and p27KIP1 in cervical carcinoma

Carcinogenesis is characterized by deregulation of the cell cycle. Although p53 is still the most important cell-cycle regulator in human malignancies, there is an increased body of evidence indicating that the aberrant expression of cyclins and cyclin-dependent kinase (CDK) inhibitors is considered as one of the most important events in malignant transformation of various human cancers. Among these cell-cycle regulators, the role of cyclin E and p27(KIP1) in the tumorigenesis of the uterine cervix has been poorly defined. Using formalin-fixed, paraffin-embedded cervical tissues, we investigated the expression of cyclin E and p27(KIP1) by immunohistochemistry, and human papillomavirus (HPV) types 16 and 18 by nested polymerase chain reaction (PCR) in 22 control cases, 23 cases with cervical intraepithelial neoplasia (CIN), and 45 patients with invasive cervical carcinoma (ICC). The p27 index (P27I) was significantly lower in patients with ICC and CIN compared to those with a normal cervix. Patients with either invasive cancer or CIN were found to have a significantly higher cyclin E index (CEI) than the controls (P<0.05). Our results were consistent with the concept that the deregulated expression of cyclin E and p27(KIP1) may play an important role in the neoplastic transformation of cervical carcinoma.

Clinical Value of Ezrin Expression in Primary Osteosarcoma

PURPOSE Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma. MATERIALS AND METHODS Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens. RESULTS Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (≥or=90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036). CONCLUSION The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.

Expression and role of estrogen receptor α and β in medullary thyroid carcinoma: different roles in cancer growth and apoptosis

Medullary thyroid carcinoma (MTC) originates from parafollicular C cells. Estrogen receptorb (ERb) expression was detected in normal parafollicular C cells and MTC tumor tissue, but ERa expression in MTC tumors still remains undetermined. The appearance and loss of ERa or ERb expression has been known to play a role in the development and progression of many human cancers. We performed immunohistochemical studies of ERa ,E Rb, and Ki67, a mitotic index, in 11 human MTC tissue samples. ERa was detected in 10 cases (91%), and ERb expression was observed in 8 cases (72 . 7%). A majority (8/10) of ERa-positive tumors showing ERb Ki67 expression was detected in three cases (27 . 3%). Neither clinical parameters nor tumor node metastasis (TNM) tumor staging was correlated with the positivity for ERs or Ki67. To investigate the biological role of each ER, we used ER-negative MTC TT cells and adenoviral vectors carrying ERa (Ad-ERa), ERb (Ad-ERb), estrogen response element (ERE)-Luc (Ad-ERE-Luc), and activator protein 1 (AP1)-Luc (Ad-AP1-Luc). Estrogen stimulated and anti-estrogen, ICI 182 780, suppressed ERE reporter activity in TT cells expressing ERa or ERb ,s uggesting that both ERs use the same classical ERE-mediated pathway. Ad-ERa infection stimulated TT cell growth; in contrast, Ad-ERb infection suppressed their growth. Apoptosis was detected in Ad-ERb-infected TT cells. Estrogen and antiestrogen suppressed AP1 activity in Ad-ERa-infected cells, whereas upon Ad-ERb infection estrogen further stimulated AP1 activity which in turn is suppressed by anti-estrogen, suggesting that each ER acts differently through a non-EREmediated pathway. Our results suggest that ERa and ERb may play different roles in MTC tumor growth and progression.

A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy

The purpose of this study was to compare 2 weekly docetaxel‐based regimens as first‐line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment‐related clinical outcomes.