Fractional Allelic Loss of Tumor Suppressor Genes Identifies Malignancy and Predicts Clinical Outcome in Follicular Thyroid Tumors

Abstract

Thyroid follicular tumors can be challenging diagnostically and clinically, because the cytologic and histologic features can be subtle and prognosis is also difficult to predict. In this study, we analyzed thyroid follicular tumors with known long-term follow-up for a molecular panel of tumor suppressor genes to determine whether this molecular approach has prognostic significance. Microdissection and DNA extraction were performed from tumor and normal tissue. Polymerase chain reaction (PCR) was performed for 13 short tandem repeats at or near tumor suppressor genes. PCR product was detected using semiquantitative capillary gel electrophoresis and fractional allelic loss (FAL) was calculated. We included eight adenomas, three minimally invasive carcinomas, four angioinvasive carcinomas, and three widely invasive carcinomas with a mean follow-up of 77 months. Three patients died of disease and an additional two are alive with disease recurrence/metastasis. The mean FAL for benign tumors (14%) was significantly different from that of malignant tumors (56%, p < 0.001). Patients with a follicular tumor who had no evidence of disease recurrence had a mean FAL of 22% and those with disease recurrence or death from disease had a mean of 78% (p < 0.002). Based on these results, a tumor suppressor gene panel for allelic imbalance in follicular-derived tumors (FTT) may correlate with both malignancy and outcome in patients with follicular-derived carcinomas of the thyroid.