Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret, Braf , ras and pax8 genes

Abstract

Expression of tpo mRNA in thyroid tumors: quantitiative PCR analysis and correlation with alterations of ret , Braf , ras and pax 8 genes AbstractImmunocytochemistry (ICC) of thyroid peroxidase (TPO) using the monoclonal antibody MoAb47 has been used as malignancy marker on thyroid fine needle aspiration. However, little is known about the fate of TPO in thyroid carcinoma. We performed a qualitative PCR (Q-PCR) analysis to measure the expression of variants of tpo mRNA in 13 normal tissue samples, 30 benign tumors (BT), 21 follicular carcinomas (FC), 20 classical papillary carcinomas (PCc), 12 follicular variants of papillary carcinomas (PCfv) and nine oncocytic carcinomas (OC). We also studied mutations involving the ras, Braf, ret or pax8 genes. Results of Q-PCR were closely correlated with those of ICC (P < 0:0001; R ¼ 0.59) and showed that overall tpo expression was lower in all carcinomas than in normal and BT (P < 0:05). The ratio tpo2 or tpo3 to tpo1 was inversed in follicular tumors. Genetic mutations were observed in 90% of PCc, 61.9% of FC, 41.7% of PCfv, 0% of OC and 10% in BT. pax8-ppar 1 rearrangement was correlated with qualitative changes in tpo mRNA (P < 0:01). These results confirmed the decrease of TPO expression in 97% of thyroid carcinomas regardless of histological type and the overexpression of shorter splice variants in follicular tumors. Both reduction in quantity of TPO and impairment of its maturation process could account for the atypical immunohistochemical reaction of MoAb47 with TPO.

BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer

“…However, our data demonstrated a significantly lower expression of both NIS and TPO mRNA in PTCs with BRAF V600E mutation with respect to negative cases. According to this finding and in agreement with the previously reported data (Di Cristofaro et al 2006, Riesco-Eizaguirre et al 2006, Durante et al 2007, we also observed a significantly lower degree of both NIS and TPO protein expression in BRAF V600E -positive cases. This finding was independent of serum TSH levels which could affect NIS mRNA and protein expression (Dohan et al 2003).…”

BRAF Mutation in Papillary Thyroid Cancer: Pathogenic Role, Molecular Bases, and Clinical Implications

“…For example, compared with RET/PTC and Ras mutation, BRAF mutation was far more profoundly associated with decrease in TPO expression in primary PTC tumors (110). It is also important to note that the correlation of BRAF mutation with abnormalities of the thyroid iodidemetabolizing machinery in PTC tumors, such as decreased expression of iodide-metabolizing genes (60, 79,97,110,146) or decreased radioiodine avidity (79,83,97), was established by comparing two groups of PTC: BRAF mutation-negative and BRAF mutation-positive. The BRAF mutation-negative group of PTC in these studies conceivably harbored other relatively common MAPK pathway-related genetic alterations, such as RET/PTC, albeit showing less severe abnormalities, consistent with a weaker effect of these genetic alterations than BRAF mutation on iodide-metabolizing genes.…”

Thyroid peroxidase and galectin-3 immunostaining in differentiated thyroid carcinoma with clinicopathologic correlation

“…The diagnostic value of TPO immunostaining was confirmed even on fine-needle aspiration [10][11][12]. However, some studies questioned the diagnostic value of MoAb 47 in clinical practice [13][14][15][16].…”