Genetic and Biological Subgroups of Low-Stage Follicular Thyroid Cancer

Abstract

Chromosomal rearrangements that create abnormal gene fusions are some of the most early and specific genetic alterations identified in cancer.

Expression profiling reveals a distinct transcription signature in follicular thyroid carcinomas with a PAX8-PPARγ fusion oncogene

“…Similarly, Du¨rig et al (2003) noticed that a large number of ribosomal and other translation-associated genes were coordinately overexpressed in CLL patients with more favorable clinical outcome. Several previous studies suggested that FTCs harboring a PAX8-PPARg are likely to be histologically more aggressive compared to those without the rearrangement (French et al, 2003;Nikiforova et al, 2003). Taken together with our data, these observations raise the possibility that a low expression of ribosomal proteins and translation-associated genes may be correlated with a more aggressive clinical course in some tumor entities.…”

“…This concept is supported by comparison of FTCs with and without the PAX8-PPARg fusion using both clustering and MDS approaches. In line with this notion, French et al (2003) demonstrated that FTCs with a PPARg rearrangement display distinct clinicopathological features. Similarly, Nikiforova et al (2003) proposed that there are at least two distinct molecular pathways involved in thyroid follicular cancer development: one initiated by RAS point mutation and the other by PAX8-PPARg rearrangement.…”

Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors

“…By immunohistochemistry, ret/PTC and PPARg are reported in o70% of papillary and follicular thyroid carcinomas, respectively, while CD10 is expressed in follicular carcinoma and follicular variant of papillary carcinoma, but not in conventional papillary thyroid carcinoma. [33][34][35][36] Therefore, a combination of multiple markers may be more sensitive than any single marker. Our study shows that a diagnostic immunohistochemical panel comprising of GAL3, FN1 and HBME1 was 100% sensitive for all follicular cellderived carcinomas.…”

An update on molecular biology of thyroid cancers

“…Deregulation of PAX8 function, essential for differentiation of thyroid cells, and induction of some other genes, that are unrelated to wild type PAX8 or PPAR␥ genes, may be responsible for generation of thyroid cancer after this rearrangement [107,108]. Generally, PAX8/PPAR␥ rearrangement is seen in follicular thyroid carcinoma at 30-35% frequency (Table 1) [109,110]. In addition, most studies have shown that this rearrangement is also seen in follicular adenomas at 2-13% frequency, and in papillary carcinomas with follicular variants at 1-5% frequency [111][112][113].…”

“…RET/PTC, BRAF, NTRK, RAS and PAX8-PPAR␥ mutations have been frequently explored for diagnosis of thyroid cancer. Gene expression profiling and microRNA studies have identified a variety of potential molecular markers to help distinguish benign from malignant thyroid neoplasms especially for nodules that are classified as indeterminate for malignancy by FNAB [36,37,45,34,[90][91][92][93][109][110][111][112][113]178,[180][181][182]. The inability to exclude malignancy in these nodules may often lead to unnecessary surgery or two step surgical procedures.…”