Biomedical subjects

Teiyu Izumi

Publications and source records attributed to Teiyu Izumi.

6 recordsLinked to original sources

PubMed2007

Dysadherin expression as a significant prognostic factor and as a determinant of histologic features in synovial sarcoma: special reference to its inverse relationship with E-cadherin expression.

Dysadherin is a cancer-associated cell membrane glycoprotein, which down-regulates E-cadherin and promotes metastasis. Synovial sarcoma is a very rare mesenchymal tumor that exhibits an epithelial profile. To confirm the diagnosis of synovial sarcoma, we evaluated several immunohistochemical markers, or detected SYT-SSX fusion gene transcript. We studied the clinicopathologic features in 92 synovial sarcoma patients and also assessed the immunohistochemical expression of dysadherin and E-cadherin to examine their possible association with histologic subtype and biologic behavior. Moreover, among 30 patients, for whom frozen materials were available, dysadherin mRNA expression was examined by reverse transcription-polymerase chain reaction and real-time quantitative reverse transcription-polymerase chain reaction analysis. Dysadherin-positive expression was significantly correlated with E-cadherin-reduced expression (P=0.0004). Dysadherin-positive immunostaining was diffusely observed in the membranes of tumor cells in 30/68 (44%) patients with monophasic fibrous type and in 1/2 (50%) patients with poorly differentiated type. However, in biphasic tumors, dysadherin expression in the fibrous component was not diffusely observed, but often sporadically or focally observed [20/22 (91%) patients]. In addition, dysadherin mRNA expression in monophasic fibrous type was significantly higher than in biphasic type (P=0.0079). Synovial sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P=0.0006). Patients with combined dysadherin-positive expression and E-cadherin-reduced expression had a significantly worse prognosis than those with other combinations of dysadherin and E-cadherin expression (P=0.0007). SYT-SSX fusion gene transcript was detected in 39 patients. In our series, SYT-SSX fusion type was found to have no correlation with histologic subtype, prognosis, or dysadherin expression. In multivariate analysis, dysadherin immunopositivity (P=0.0411) was an independent adverse prognostic factor, in addition to a high MIB-1 labeling index (> or =10%). We conclude that E-cadherin dysfunction by dysadherin is associated with reduced E-cadherin expression and morphologic change from epithelioid to spindle phenotype. Dysadherin expression is considered to be one of the determinants of histologic subtype in synovial sarcoma. Moreover, dysadherin expression is an excellent and independent prognostic indicator.

Adult↗

PubMed2006

Intramuscular diffuse-type giant cell tumor within the hamstring muscle.

Diffuse-type giant cell tumor (D-TGCT) is known as a synonym for pigmented villonodular synovitis (PVS), a condition usually found in the large joints. We report an extremely rare case of D-TGCT which was located within the hamstring muscle. The lesion was an incidental finding in a 62-year-old man who underwent positron emission tomography (PET) as part of a staging evaluation for gastric cancer. The lesion was resected. There has been neither metastasis nor recurrence during the 6-month period since resection. This case demonstrates that PVS/D-TGCT may have a high SUV on PET imaging, and for this reason PET may be useful for detecting both the tumor and any recurrence.

Buttocks↗

PubMed2006

Chromosomal aberrations and microsatellite instability of malignant peripheral nerve sheath tumors: a study of 10 tumors from nine patients.

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon soft tissue neoplasm with a poor prognosis, occurring sporadically or associated with neurofibromatosis type 1 (NF1); however, the histogenesis of MPNST remains unclear, especially in sporadic tumors. There are two major forms of genomic instability in human cancer: chromosomal instability (CIN) and microsatellite instability (MSI). An inverse relationship has recently been demonstrated between CIN and MSI in colorectal cancers. CIN and MSI are suggested to be individual pathways, which are involved in the pathogenesis and which may lead to specific clinical and pathological characteristics. To elucidate the chromosomal aberration as a consequence of CIN and MSI status of MPNST, we karyotyped 10 MPNSTs from nine patients, and examined the MSI of seven microsatellite markers using high-resolution fluorescence microsatellite analysis; 2 out of 10 cases (20%) had normal karyotypes, and 8 out of 10 cases (80%) revealed structural and numerical chromosomal aberrations. Three of the 10 cases (30%) showed near triploidy. The most frequent aberration was -22 (40%), followed by +2, +14, -13, -17, and -18 (30% each). An MSI-low status was observed in 30% of cases; the remaining cases showed microsatellite stability. These findings suggest that chromosomal aberration as a consequence of CIN has a greater role in the pathogenesis of MPNST than does that due to MSI.

Adult↗

PubMed2006

Aberrant expression of CHFR in malignant peripheral nerve sheath tumors.

Mitotic checkpoint maintains genomic integrity before mitosis. Numerous observations have suggested that mitotic abnormalities produce chromosomal instability and aneuploidy. In MPNST, complex karyotypes showing numerical and structural aberrations have been described. 'Checkpoint with forkhead-associated domain and ring finger' (CHFR) was recently identified as defining a new early mitotic checkpoint. We examined the expression of CHFR in 96 cases of MPNST by immunohistochemical and molecular methods. We found reduced (score, < or = 3) expression of CHFR in 63 out of 96 (66%) cases of MPNST, and such alteration was significantly correlated with a high mitotic count, a high Ki-67-labeling index, and a poor prognosis. In addition, MPNST with normal karyotype showed a strong (score, =5) expression of CHFR. Our results support the assertion that CHFR functions as an inhibitor of tumor proliferation.

Adolescent↗

PubMed2006

Prognostic significance of dysadherin expression in epithelioid sarcoma and its diagnostic utility in distinguishing epithelioid sarcoma from malignant rhabdoid tumor.

Dysadherin is a cancer-associated cell membrane glycoprotein, which downregulates E-cadherin and promotes metastasis. We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases. In addition, we compared dysadherin mRNA expression between epithelioid sarcoma and malignant rhabdoid tumor cell lines, using RT-PCR and real-time quantitative RT-PCR analysis. Immunohistochemical dysadherin expression was more frequently observed in proximal-type epithelioid sarcoma (71%) in comparison with distal-type epithelioid sarcoma (36%) (P = 0.037). Furthermore, seven proximal-type epithelioid sarcoma cases mimicking malignant rhabdoid tumor (histologically classified as the large cell type, accompanied by frequent rhabdoid cells and located in deep soft tissue) were all positive for dysadherin (100%), whereas dysadherin expression was not detected at all in any of the true six malignant rhabdoid tumors (0%). Cell lines established from proximal-type epithelioid sarcoma revealed significantly higher levels of dysadherin mRNA expression, compared with the levels seen in malignant rhabdoid tumor cell lines by real-time quantitative RT-PCR (P = 0.0433). Epithelioid sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P = 0.001). In multivariate analysis, dysadherin immunopositivity (P = 0.0004) was one of the two independent adverse prognostic factors. We conclude that dysadherin expression in epithelioid sarcoma is a significant poor prognostic factor and that it is a powerful diagnostic marker for distinguishing epithelioid sarcoma, including the proximal-type epithelioid sarcoma, from malignant rhabdoid tumor. In epithelioid sarcoma, especially in proximal-type epithelioid sarcoma, increased cell disadhesion and motility by dysadherin plays an important role to acquire aggressive biological behavior. However, in malignant rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin.

Biomarkers, Tumor↗

PubMed2005

Alterations of the RB1 gene in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma is a malignant adipocytic neoplasm containing a non-lipogenic sarcoma of variable histological grade that arises against the background of a pre-existing well-differentiated liposarcoma. The phenomenon of dedifferentiation is considered to be time-dependent, but the mechanism is not well known. The retinoblastoma protein, encoded by the RB1 gene located at 13q14, is a key regulator of proliferation, development, and differentiation of certain cell types, including adipocytes. In the current study, we investigated the genetic alterations of the RB1 gene, such as mutation (the essential promoter region and the protein-binding pocket domain; exons 20-24) and methylation of the promoter region, in addition to pRB expression and loss of heterozygosity (LOH) status, in two morphologically distinct areas (non-lipogenic dedifferentiated and well-differentiated components) in 27 patients. As a control, 11 undifferentiated high-grade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma samples and 11 well-differentiated liposarcoma samples were also evaluated. Dedifferentiated components showed LOH (15/25; 60%) and abnormal retinoblastoma protein expression (18/27; 66.7%) more frequently than noted in the well-differentiated components (3/24; 12.5% and 9/27; 33.3%, respectively). Five and four out of the 27 dedifferentiated components harbored mutations and promoter methylation, respectively, whereas none of these alterations were seen in the well-differentiated components. These results suggest that retinoblastoma protein has a major role to play in dedifferentiation and that a 'two-hit' mechanism is involved in the altered retinoblastoma protein expression in dedifferentiated liposarcoma.

Adult↗