Loss of heterozygosity of the VHL gene identifies malignancy and predicts death in follicular thyroid tumors

Background. Follicular thyroid tumors (FTT) usually require resection to distinguish adenoma from carcinoma. Better markers that predict histologic subtype and prognosis are needed for FTT. Methods. Seventeen benign and malignant FTT with follow-up were selected. Pathologic diagnosis was confirmed, tumor and normal tissue were microdissected, and DNA was extracted. Polymerase chain reaction (PCR) products for a microsatellite marker at the von Hippel Lindau gene (VHL) gene locus (3p26) were analyzed with semiquantitative capillary gel electrophoresis to detect loss of heterozygosity (LOH). Data were assessed for statistical significance with χ². Results. Mean follow-up was 77 months (range 29 to 120 months). Four cases were uninformative (homozygous microsatellite). Among 13 evaluable patients (6 adenomas, 7 follicular cancers) LOH of VHL was present only in carcinomas (P = .013). LOH was present in 4/4 patients with recurrence and 0/3 patients without recurrence (P = .017). Death from disease has occurred in 3 patients. LOH of VHL was strongly associated with death from disease (T = .034). Conclusions. FTT can be analyzed for LOH at the VHL gene locus. In this initial study, LOH of VHL was highly specific for malignancy and predicted death from disease. The analysis of VHL may provide for preoperative detection in cytologic samples with potential impact on clinical management of FTT.