Endocrine Abstracts

Introduction: Identification of molecular markers with a reliable prognostic value may greatly improve the management of patients with papillary thyroid carcinoma (PTC). Rac1b, a hyperactive splice variant of the small GTPase Rac1, was found to be overexpressed in colorectal, breast and lung cancer. It has been shown to sustain tumor cell survival in colorectal cancer and was reported to have a key role in the malignant progression of breast and lung tumors. The Rac1b tumorigenic proprieties led us to investigate whether Rac1b was expressed in PTCs.

Patients and methods: The expression of Rac1b at transcript level was analyzed in a total of 61 PTC patients (mean age 41 years; F:M ratio 43:19) by qRT-PCR. In 23 cases, tumor and the corresponding normal paired sample were compared. Rac1b expression at protein level was confirmed by western blot and immunohistochemistry in selected representative cases. Patients were divided into two groups based on longitudinal analysis and final outcome (mean follow-up 6-years): group I included patients that underwent full sustained remission after initial treatment or presented stable residual biochemical disease; group II included patients with persistence of disease after primary treatment, patients with at least one relapse and those who died from disease.

Results: Rac1b expression in thyroid tissue was clearly detected at both transcript and protein levels. Moreover, we observed that Rac1b was overexpressed in 46% of PTCs and found a striking correlation between poor clinical outcome and Rac1b overexpression (P=0.0029).

Conclusions: Present results document expression of Rac1b in normal thyroid cells as well as overexpression in a subset of PTCs. Whether Rac1b actively participates in thyroid tumorigenesis will require further investigation. Also, future studies are needed to validate its use as a prognosis marker.