Immunophenotype characterization of poorly differentiated breast carcinomas

Author(s)

Roberta Possato Fernandes

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2009-02-18

Examining board members

Ileana Gabriela Sanchez de Rubio; Rosalinda Yossie Asato de Camargo; Janete Maria Cerutti; Maria Lucia Cardillo Correa Giannella; Laura Sterian Ward

• Advisor: Geraldo Antonio de Medeiros Neto; Ileana Gabriela Sanchez de Rubio

Abstract

The differentiated thyroid carcinoma (DTC) encloses 95% of all thyroid malignant disease. In USA, it increased 2,4 times in recent years (1973- 2002). The treatment includes total thyroidectomy, ablation with radioiodine (RAI) followed by TSH suppression with L-Thyroxine. The cancer recurrence occurs in 20% of the cases. Periodic evaluation through imaging examinations and serum thyroglobulin (TG) measurements by imunoassays method is recommended for careful follow-up of these patients. The anti-TG antibodies prevalence is 15-25% and would impair, partially, the serum TG use as a tumor marker. An alternative method to identify the recurrence of the tumor is the thyroid cells detection in peripheral blood, through the TG messenger RNA quantification (mRNA-TG) by real time RT-PCR. This new methodology increases the sensitivity detection for this molecule. The objective of this study was to verify the mRNA-TG peripheral blood quantification significance, as a complementary diagnostic method in the long term follow up of patients with DTC. Fourty five blood samples from patients with DTC have been collected before and 24, 48, 72 hours, 7 days, 1, 3, 6, 9 months, 1, 2, 4, 5, 6 and 7 years after the ablation therapy. Extensive technique standardization for mRNA-TG measurements was carried out to exclude methodological interventions and two housekeeping genes (GAPDH and HPRT1) were used to calculate the mRNA-TG concentrations. Concomitantly, serum TG measurements, hormonal profile and antibodies anti-TG assays were performed. The whole body scan was performed 7 days after RAI ablation to determine the stage of the disease. It was not possible to establish a cut-point value for mRNA-TG. The mRNA-TG did not differentiated the clinical stage of the disease in the long term follow-up and neither in the presence of anti-TG antibodies and TSH30ng/mL. Serum TG was able to differentiate the clinical stage of the patients during the follow-up. In conclusion mRNA-TG is not a good marker for the DCT recurrence, even when technical standardization, long term evaluation and the presence of antibodies anti-TG were considered. Thus it could not be used as a complementary diagnostic method in the DTC patients follow-up. This study confirmed the high sensivity of the real time RT-PCR whereas with very low specificity, consequently is unviable to be used in the DTC patients follow-up (AU)