Changes of expression level of the differentiation markers in papillary thyroid carcinoma under thyrotropin suppression therapy in vivo immunohistochemical detection of thyroglobulin, thyroid peroxidase, and thyrotropin receptor.

BACKGROUND AND OBJECTIVES: Differences in the expression levels of Thyroglobulin (Tg), Thyroid peroxidase (TPO) and thyrotropin receptor (TSH-R) in primary and recurrent specimens under a suppressive serum TSH condition were elucidated in 26 papillary carcinoma patients. METHODS: Immunohistochemical detection was performed by use of each monoclonal antibody against Tg, TPO, and TSH-R. The staining concentrations of the three markers in each specimen were measured for comparison. RESULTS: The mean staining concentrations of Tg, TPO, and TSH-R in the entire primary tumor were 103.92, 104.6 and 89.25, respectively. Five cases showed stronger expression of all the differentiation markers and eight cases showed weaker expression of all these markers in recurrent tissue than in primary tumors. The weaker expression of TSH-R at the recurrent site as compared with that at the primary site significantly demonstrated the shortness of the disease free interval or overall survival. There were significant differences between the death due to cancer and the weaker expression of TSH-R in the recurrent tumor as compared with that in the primary tumor. CONCLUSIONS: Under the TSH suppressive condition, the markers were not expressed uniformly among recurrent tumors. Even under that state, however, low expression of TSH-R in the recurrent tissue was strongly related to a poorer outcome in the patients.

Semi-quantitative comparison of the differentiation markers and sodium iodide symporter messenger ribonucleic acids in papillary thyroid carcinomas using RT-PCR.

OBJECTIVE: To investigate the levels of expression of the sodium iodide symporter (NIS) and three differentiation markers (thyroglobulin (Tg), thyroid peroxidase (TPO) and thyrotrophin receptor (TSH-R)) in 35 patients with primary (n=31) or recurrent (n=4) papillary thyroid carcinoma, and to compare the findings with clinical data. METHODS: We performed a multiplex semi-quantitative RT-PCR to analyse the relative levels of expression of Tg, TPO and TSH-R mRNAs, and a separate semi-quantitative RT-PCR for NIS mRNA. RESULTS: Tg, TPO and TSH-R mRNAs were expressed in all the patients, whereas NIS mRNA was expressed in all but eight. Analysis of the expression of the differentiation markers in all patients showed a significant correlation among Tg, TPO and NIS. With regard to the relationship between the expression of each gene and the MACIS score, there was significant correlation only for the Tg gene (P<0.05). CONCLUSIONS: The levels of expression of NIS mRNA correlated significantly with those of Tg and TPO mRNAs, but not with those of TSH-R mRNA. The relationship with clinical stage and prognostic score, however, varied among these differentiation markers.

Analyses of the outcome of locally invasive papillary thyroid carcinomas.

We retrospectively analyzed the outcome for patients with locally invasive papillary carcinoma. The study group comprised 40 patients with locally invasive papillary thyroid carcinoma first diagnosed between 1981 and 1995. The enrolled patients were divided into two groups according to whether they underwent complete resection (n = 19) or not (n = 21). All patients were followed-up for a maximum of 206 months and a minimum of 33 months until 1998. There were no significant differences among these two groups with regard to age, sex, or tumor size. Recurrence of the disease was recognized in four patients in the complete resection group and ten in the incomplete group. There were no significant differences in the recurrence rate between both groups. Five patients from the incomplete resection group died of disease, and all patients from the complete resection group were alive. The percentage of surviving patients in the complete resection group was significantly higher than that in the incomplete group. The 15-year survival rates of the complete resection group and incomplete resection group were 100% and 74.2%, respectively. The 15-year survival rate of patients younger than 45 years in the incomplete resection group was 100%. The 15-year survival rate of the complete resection group was significantly higher than that of the incomplete group. In conclusion, complete resection without tumor residue should be performed for patients older than 45 years.

[Doxifluridine decreases serum levels of interleukin-6 in a cancer cachexia model].

Cancer cachexia is a common paraneoplastic syndrome in patients with advanced malignancies. However, the mechanisms of the development of cancer cachexia remain to be elucidated. Interleukin (IL)-6 is known to be involved in the development of cancer cachexia. The KPL-4 human breast cancer cell line, which was recently established in our laboratory, secretes IL-6 into the culture medium. Oral administration of doxifluridine (5'-DFUR, 60 mg/kg or 120 mg/kg) significantly inhibited the growth of KPL-4 tumors, reduced the tissue levels of IL-6, and alleviated body weight loss. Serum IL-6 levels were also lowered by 5'-DFUR in nude mice bearing KPL-4 tumors. Additionally, it is suggested that tumor necrosis factor (TNF)-alpha is involved in the cachexia induced by KPL-4 tumors. We suggest that 5'-DFUR suppresses cancer cachexia by lowering IL-6 levels in the tumor tissues and serum.