Biomedical subjects

Fumio Matsuzuka

Publications and source records attributed to Fumio Matsuzuka.

At least 55 records · Page 3Linked to original sources

PubMed2004

Prognosis after reoperation for local recurrence of papillary thyroid carcinoma.

PURPOSE: To investigate the factors associated with a favorable prognosis after reoperation for local recurrent papillary thyroid carcinoma (PTC), we reviewed 45 patients who underwent surgery for first local recurrence of PTC. METHODS: We divided the patients into two groups. Group A (n = 28) had no second recurrence, and group B (n = 17) had second local recurrence after surgery for recurrence. RESULTS: The mean follow-up period after reoperation was 56.9 months. The mean age at the time of reoperation in group A was significantly lower than that in group B, at 48.1 years versus 62.3 years, respectively (P = 0.0007). The mean age at the time of the initial operation in group A was also significantly lower than that in group B, at 40.1 years versus 55.1 years, respectively (P = 0.0006). Patients with recurrent tumors only outside the area dissected at the initial operation (n = 27) had a better outcome than those with recurrence within the dissected area (n = 18; P = 0.0127). Patients who underwent systematic partial or modified neck dissection (n = 36) had a better outcome than those who underwent only simple local resection (n = 9; P = 0.0169). CONCLUSION: For local recurrent PTC, systematic neck dissection is recommended over local resection of recurrent tumors.

Adult↗

PubMed2004

Maspin expression is directly associated with biological aggressiveness of thyroid carcinoma.

Maspin belongs to the serpin superfamily and has been identified as a tumor suppressor because it inhibits cell motility, invasion, and angiogenesis. However, its physiological activity in carcinoma tissues seems to differ according to the origin of the carcinoma. In this study, we investigated maspin expression in thyroid neoplasms originating in follicular cells by means of immunohistochemistry. Neither normal follicular cells nor stromal cells expressed maspin. Follicular adenomas were all negative for maspin, but 12.5% of follicular carcinomas and 30.5% of papillary carcinomas were positive for it. However, the staining pattern was only focal in all positive specimens except for one and maspin-expressing cells were present mainly at the edge of carcinoma nests. Widely invasive follicular carcinomas tended to be more frequently positive for maspin than minimally invasive ones. In papillary carcinoma, maspin expression was directly linked to stage, tumor size, and extrathyroidal invasion. Papillary and follicular carcinomas involving lesions with solid, trabecular, or scirrhous growth patterns (poorly differentiated carcinoma as designated by Sakamoto et al.) expressed maspin in significantly higher incidence than those with pure papillary or follicular patterns. Furthermore, 48.2% of anaplastic (undifferentiated) carcinomas diffusely expressed maspin, and the rest were completely negative. These findings indicate that, in contrast to other carcinomas, maspin expression is directly associated with the biological aggressiveness of thyroid carcinoma. Further studies regarding the function of maspin in this carcinoma are required.

Cysteine Proteinase Inhibitors↗

PubMed2004

Increased intensities of fas expression on peripheral T-cell subsets in severe autoimmune thyroid disease.

Fas (CD95)-Fas ligand (FasL; CD178)-induced apoptosis is necessary for the maintenance of self-tolerance. To clarify whether or not any abnormalities in the Fas-FasL system exist in patients with autoimmune thyroid disease (AITD), we examined the expression of Fas and FasL on peripheral T lymphocytes by three-color flow cytometry in 113 patients with AITD and 49 healthy controls. The intensities of Fas expression in both CD4(+) and CD8(+) T cells decreased in thyrotoxic patients with Graves' disease (GD), but increased in both patients with severe Hashimoto's disease (HD) undergoing treatment and seriously intractable patients with GD continuously positive for thyrotropin (TSH) receptor antibody despite treatment with antithyroid drugs for more than 5 years. The proportion of Fas expression was increased in CD4(+) T cells from patients with untreated GD, and in CD8(+) T cells from patients with severe HD. The proportion of CD8(+) T cells decreased in patients with severe HD. FasL were not expressed on T cells in controls and patients with AITD. These results indicate that (1). the intensities of Fas expression on peripheral T cells increase in severe autoimmune thyroid diseases and (2). both the intensity and the proportion of Fas expression may be important for the induction of apoptosis.

Adult↗

PubMed2004

Increase of serum interleukin-10 in intractable Graves' disease.

The intractability of Graves' disease (GD) and the severity of Hashimoto's disease (HD) vary among patients. We previously reported that peripheral immunoglobulin (Ig) G3-secreting cells were increased in patients with intractable GD (i.e., requiring continuous antithyroid drug therapy). Isotype switching to IgG3 is induced by interleukin (IL)-4 and IL-10. To clarify which of these cytokines is related to the intractability or severity of autoimmune thyroid disease (AITD), we examined the serum concentrations of IL-10 and IL-4 by enzyme immunoassay in 166 patients with AITD and in 53 healthy controls. The serum IL-10 concentration was significantly higher in patients with GD and continuously positive for thyrotropin (TSH) receptor antibody (TRAb) despite more than 5 years of antithyroid drugs treatment than in patients with GD in remission. The serum IL-4 concentration did not differ between these two groups of patients. However, the serum IL-10 concentration was not related to the severity of HD. These results indicate that IL-10, but not IL-4, is related to the intractability of GD, but not to the severity of HD.

Adult↗

PubMed2004

Intrathyroidal CD4+ T lymphocytes express high levels of Fas and CD4+ CD8+ macrophages/dendritic cells express Fas ligand in autoimmune thyroid disease.

In autoimmune thyroid disease (AITD), the proportion of CD4 lymphocytes is lower in the thyroid than in the peripheral blood. We examined both Fas and Fas ligand (FasL) expression in lymphocyte subsets and nonlymphoid mononuclear cells including monocytes, macrophages, and dendritic cells (M/DCs) in both peripheral blood and thyroid specimens from 11 patients with Graves' disease and 1 with Hashimoto's disease by three-color flow cytometry. Proportions and intensities of Fas expression were increased in CD4 single-positive (SP) (CD4(+) CD8(-)), CD8 SP (CD8(+) CD4(-) ), and CD4(+) CD8(+) double-positive (DP) lymphocytes in AITD thyroids compared to those in blood, and were much higher in CD4(+) (CD4 SP and DP) lymphocytes than in CD8 SP lymphocytes in the thyroid. In the blood, most M/DCs expressed only CD4, but approximately 60% of M/DCs expressed both CD4 and CD8 in AITD thyroid. The proportion of DP M/DCs expressing FasL was higher in thyroid than in blood; proportion and intensity of FasL expression were much higher in DP M/DCs than in CD4 SP and CD8 SP M/DCs in the thyroid. These data indicate that increased Fas expression in intrathyroidal CD4(+) T lymphocytes may be the cause of CD4 lymphocyte reduction in AITD thyroid, and that intrathyroid DP M/DCs with high FasL expression may be related to the reduction in AITD.

Adult↗

PubMed2004

Expression of the components of the Cip/Kip family in malignant lymphoma of the thyroid.

OBJECTIVE: For evaluating the characteristics of human neoplasms, investigation of regulators of cell cycle progression is important. We studied three components of the Cip/Kip family, p57, p27 and p21, in malignant lymphomas of the thyroid. METHODS: We immunohistochemically investigated the expression of the three proteins for 49 cases of thyroid lymphomas, as well as 10 cases of chronic thyroiditis. RESULTS: In infiltrating lymphocytes in chronic thyroiditis, p57 and p27 were diffusely expressed, whereas p21 immunoreactivity was only occasionally observed. In lymphoma, decreased expression of p57 (less than 50% of lymphoma cells were positive) was observed in 24 cases (49.0%). p57 expression was inversely linked to the MIB-1 labeling index, grade of malignancy and aberrant p53 expression. Decreased expression of p27 was observed in 25 cases (51.0%), which was also related to the MIB-1 labeling index and aberrant p53 expression. On the other hand, p21 expression was occasional, and when the cut-off value was set at 3%, 38 cases (77.6%) were regarded as negative. P21 expression was not linked to any clinicopathological parameters. CONCLUSION: These findings suggest that, among the 3 components of the Cip/Kip family, p57 and p27 play a role in negatively regulating the cell proliferation of thyroid lymphoma cells and decreased expression of them contributes to the progression of this disease.

Biomarkers, Tumor↗

PubMed2004

S100A4 expression is an early event of papillary carcinoma of the thyroid.

OBJECTIVES: S100A4 is a calcium-binding protein related to the metastatic potential of carcinoma. In order to elucidate its contribution to the progression of thyroid carcinoma, we investigated S100A4 expression in various thyroid neoplasms. METHODS: We immunohistochemically examined S100A4 expression in 195 cases of thyroid neoplasms. RESULTS: Although S100A4 was absent in normal follicular cells and follicular adenoma, S100A4 was positive in all 115 cases of papillary carcinoma examined, including 58 microcarcinomas. However, a significant relationship could not be established between S100A4 expression and clinicopathological features of papillary carcinoma. In follicular carcinoma, the widely invasive type expressed S100A4 more frequently than the minimally invasive type (p = 0.0028). In anaplastic carcinoma, S100A4 was expressed in 61.9% of cases, but the incidence was significantly lower (p < 0.0001) than that in papillary carcinoma. CONCLUSIONS: These findings suggest that (1) S100A4 plays a constitutive role in papillary carcinoma and (2) S100A4 may be a useful marker for early the detection of this carcinoma.

Adenocarcinoma, Follicular↗

PubMed2004

Cdc25A and cdc25B expression in malignant lymphoma of the thyroid: correlation with histological subtypes and cell proliferation.

Cdc25B and cdc25A phosphatases are representative stimulators of cell cycle progression, and recent studies have also indicated their oncogenic roles. In this study, we investigated the expression of these phosphatases in malignant lymphoma of the thyroid by immunohistochemistry. These phosphatases were not expressed in follicular cells in normal follicles, but were heterogeneously or diffusely expressed in the follicles in chronic thyroiditis and malignant lymphoma. In infiltrating lymphocytes in chronic thyroiditis, they were only occasionally expressed. Of the 47 cases of lymphoma, 30 (63.8%) were classified as high group for cdc25B because it was expressed in more than 25% of lymphoma cells. Cdc25B expression level was inversely associated with MIB-1 labeling index (p=0.0008), and aberrant p53 expression (p=0.0077). Furthermore, cases of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MZBL) were more frequently classified as high group (p=0.0318) than those of diffuse large B-cell lymphoma (DLBL). On the other hand, 22 cases (46.8%) were regarded as high group for cdc25A, but its expression level was not linked to those parameters. These findings suggest that i) cdc25B plays a role in the early phase of thyroid lymphoma possibly including the malignant transformation from chronic thyroiditis, and ii) cdc25A may contribute to the progression of lymphoma.

Cell Cycle Proteins↗

PubMed2003

Expression and cellular localization of p8 protein in thyroid neoplasms.

OBJECTIVES: p8 protein has mitogenic activity and is linked to the development of pancreatic carcinoma. However, little is known about the expression and physiological significance of this protein in other human carcinomas. METHODS: In this study, we immunohistochemically investigated p8 expression in thyroid neoplasms as well as in the normal thyroid gland. RESULTS: p8 was expressed in normal follicular cells, but no normal thyroid was regarded as overexpressing p8. On the other hand, 44.3% of papillary carcinoma overexpressed p8 and the incidence was directly linked to the tumor size (p=0.0340) and lymph node metastasis (p=0.0145). In follicular tumors, the incidence of p8 overexpression did not depend on histological type. In anaplastic (undifferentiated) carcinoma, p8 was overexpressed only in 5.0%, which was significantly lower than in papillary (p=0.0006) and follicular carcinomas (p=0.0049). In normal follicules and follicular tumors, p8 was localized mainly in the nucleus except for two adenomas. On the other hand, p8 localization was more cytoplasmic in papillary carcinoma larger than 1.0 cm (p=0.0186) and with a poorly differentiated lesion (p=0.0313). CONCLUSIONS: These results suggest that the overexpression and cytoplasmic localization of p8 protein may reflect disease progression of papillary carcinoma, whereas this protein plays little part in thyroid carcinoma after anaplastic transformation.

Adenocarcinoma, Follicular↗

PubMed2003

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid.

14-3-3 sigma is a negative regulator of the cell cycle and contributes to G2 arrest. Thus far, the lack of its expression due to hypermethylation of the CpG islands has been reported in some carcinomas. In this study, we investigated the expression of 14-3-3 sigma in thyroid neoplasms by means of immunohistochemistry as well as Western blot analysis. Normal follicules did not express 14-3-3 sigma. In 82 papillary carcinomas, all the cases expressed 14-3-3 sigma and its expression was not reduced but even enhanced in the advanced stage and in poorly differentiated types. Furthermore, 21 of the 23 anaplastic carcinomas expressed 14-3-3 sigma and its expression level tended to be higher than in papillary carcinoma. On the other hand, none of the 34 follicular carcinomas or 29 follicular adenomas expressed 14-3-3 sigma. These results suggest that 14-3-3 sigma plays a constitutive role in papillary carcinoma rather than acting as a cell cycle regulator, whereas it is not required for the occurrence and development of follicular tumor.

14-3-3 Proteins↗

PubMed2003

Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation.

Previous studies have demonstrated that terminal fucosylation is associated with the biological aggressiveness of carcinomas, but the significance of core fucosylation (alpha1,6-fucosylation) through alpha1,6-fucosyltransferase (FUT8) has not been studied in depth. Herein, we investigated the expression of alpha1,6-fucosyltransferase (FUT8) in 133 cases of thyroid carcinomas using an immunohistochemical approach. The expression of FUT8 was quite low in normal follicules. A high expression of FUT8 was observed in 33.3% of papillary carcinoma and the incidence was directly linked to tumor size and lymph node metastasis. In contrast, this phenomenon was less frequently observed in follicular carcinoma and anaplastic (undifferentiated) carcinoma. These results suggest that FUT8 expression may be a key factor in the progression of thyroid papillary carcinomas, but not follicular carcinomas, and decreases in FUT8 expression might be linked to anaplastic transformation.

Carcinoma↗

PubMed2003

Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors.

We measured the relative expression levels of galectin-3 mRNA to beta-actin mRNA in normal thyroid tissues, thyroid tumor tissues and thyroid-derived fibroblasts. Galectin-3 mRNA was expressed ubiquitously in both benign and malignant thyroid tumors. Although a significant increase in its expression was observed in papillary carcinomas, no significant difference was observed between follicular carcinomas and adenomas. In contrast to the previous optimistic reports using immunohistochemical analysis of the galectin-3 protein expression, these results demonstrate that galectin-3 mRNA may not be a suitable target for molecular-based diagnosis of thyroid carcinomas.

Adenocarcinoma, Follicular↗

PubMed2003

14-3-3 sigma possibly plays a constitutive role in papillary carcinoma, but not in follicular tumor of the thyroid.

Jun activation domain-binding protein 1 (jab1) is known as a coactivator of the AP1 transcription factor. Recent studies have demonstrated that jab1 contributes to carcinoma progression by degrading p27/Kip1 protein. In this study, we immunohistochemically investigated jab1 expression in thyroid neoplasms. jab1 overexpression tended to be frequently observed in follicular carcinoma compared to adenoma. Larger-sized papillary carcinoma overexpressed jab1 in higher incidence than microcarcinomas (1.0 cm or less in maximum diameter). In anaplastic carcinoma, jab1 was more frequently overexpressed than in papillary and follicular carcinomas. An inverse relationship was detected between jab1 overexpression and p27 expression in papillary and anaplastic carcinomas, but not in follicular tumor. These results suggest that jab1 plays a role in the progression of thyroid carcinomas, especially those of aggressive phenotypes, and it may be responsible for p27 degradation in anaplastic and papillary carcinomas.

14-3-3 Proteins↗

PubMed2003

p130 expression in thyroid neoplasms: its linkage with tumor size and dedifferentiation.

p130 belongs to the retinoblastoma-related gene family, and its gene product works to negatively regulate cell cycle progression in the G1 phase. In this study, we investigated p130 expression in thyroid neoplasms. p130 overexpression was observed in 33.3% of follicular adenoma and 50% of follicular carcinoma and the incidences were not significantly different. In papillary carcinoma, it was overexpressed in 36.5% of cases, but in microcarcinoma, the incidence was significantly lower (14.3%). Furthermore, in anapalstic carcinoma, p130 overexpression was less frequently seen than in papillary carcinoma except for microcarcinoma and follicular carcinoma, and only 14.3% of cases overexpressed this protein. These findings suggest that: (1) reduced p130 expression may contribute to the aggressive character of anplastic carcinoma; and (2) p130 may specify the growth characteristics of microcarcinoma.

Carcinoma↗

PubMed2003

Encapsulated anaplastic thyroid carcinoma without invasive phenotype with favorable prognosis: report of a case.

We herein report a case of anaplastic thyroid carcinoma in a 77-year-old woman with long-term disease-free survival. The tumor measured 7.5 x 6.0 cm in size and was diagnosed to be anaplastic carcinoma. We investigated the biological aggressiveness of this carcinoma by means of immunohistochemistry and found it have a high cell-proliferating activity, a disruption in the mechanism of apoptosis, and a high potential of cell spreading, similar to that observed in usual anaplastic carcinomas. The only unique point was that this tumor was encapsulated and no invasion of carcinoma cells beyond the capsule was microscopically observed. To avoid an obstruction of the trachea, a lobectomy without lymph node dissection was performed as a "palliative operation." Although neither adjuvant chemotherapy nor radiotherapy was carried out due to her age, she has nevertheless survived with no evidence of recurrence for 57 months after surgery. The presence of such a type of anaplastic carcinoma should thus be noted by surgeons and pathologists, even though the occurrence of such cases seems to be very rare.

Aged↗

PubMed2003

Y-box binding protein expression in thyroid neoplasms: its linkage with anaplastic transformation.

Recent studies have demonstrated that Y-box binding protein (YB-1) regulates the transcription of genes linked to carcinoma progression. In this study, we investigated the expression of this protein in thyroid neoplasms to elucidate its significance. The expression of YB-1 was immunohistochemically investigated using the monoclonal antibody for various thyroid neoplasms. Normal follicles did not overexpress YB-1, and only moderate overexpression of YB-1 was observed in some follicular tumors and papillary carcinoma, especially those of a larger size. In contrast, 92.9% of anaplastic carcinoma strongly overexpressed YB-1. YB-1 immunoreactivity was seen in both cytoplasms and cell nuclei, but the former was more predominant. These findings suggest that YB-1 plays a role in regulating the transcription as well as translation of genes contributing to the anaplastic transformation of thyroid carcinoma.

Adenocarcinoma, Follicular↗

PubMed2003

KAI1 expression in thyroid neoplasms: its linkage with clinicopathologic features in papillary carcinoma.

KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. Previous studies have shown that the down-regulation of KAI1 mRNA and decreased expression of its gene product are significantly linked to carcinoma progression, including metastatic ability. In this study, we investigated KAI1 protein expression in thyroid neoplasms. KAI1 overexpression was observed in 64.0% of papillary carcinoma cases, and the incidence was significantly higher than in cases of follicular carcinoma (20.0%) (p = 0.0001). In papillary carcinomas, decreased KAI1 expression was frequently observed in cases invading beyond the thyroid capsule (p = 0.001), as well as in lymph node metastases (p = 0.0047) and poorly differentiated lesions (p = 0.0299). Furthermore, in anaplastic carcinoma, the incidence of KAI1 overexpression was lower than in papillary carcinoma (p < 0.0001), and only 4.2% of the cases overexpressed this gene. These results suggest that KAI1 down-regulation is significantly related to the progression of papillary carcinoma, including lymph node metastasis, and its anaplastic transformation.

Adenocarcinoma, Follicular↗

PubMed2003

Cdc2 expression in primary thyroid lymphoma: its relationship with biological aggressiveness and G2 cyclins.

Previous studies have demonstrated that the G2-M modulators contribute to the progression of human neoplasms. In this study, we investigated the expression of these modulators, cyclin-dependent kinase 1 (cdc2), and G2 cyclins, cyclin A and cyclin B1, in primary thyroid lymphoma. Cdc2 immunoexpression was observed in 51.0% of the 49 cases examined and was related to grade of malignancy, high Ki-67 labeling index, and aberrant p53 expression. The incidences of immunoexpression of cyclin A and cyclin B1 were 63.3% and 40.9%, respectively, and they were also related to the above three parameters. Furthermore, a correlation was found between the immunoexpression of cdc2 and G2 cyclins. These findings suggest that the cdc2 and G2 cyclins play an important role in the progression of thyroid malignant lymphoma.

Biomarkers, Tumor↗