Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors

Germline mutations In PTEN (MMAC1/TEP1) are found in patients with Cowden s yndrome, a familial cancer syndrome which is characterized by a high risk o f breast and thyroid neoplasia, Although somatic Intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, los s of heterozygosity (LOH) has been reported in up to one fourth of follicul ar thyroid adenomas (FAs) and carcinomas, In this study, we examined PTEN e xpression In 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiat ed thyroid carcinomas) using immunohistochemistry and correlated this to th e results of LOH studies. Normal follicular thyroid cells showed a strong t o moderate nuclear or nuclear membrane signal although the cytoplasmic stai ning was less strong. In FAs the neoplastic nuclei had less intense PTEN st aining, although the cytoplasmic PTEN-staining intensity did not differ sig nificantly from that observed in normal follicular cells. In thyroid carcin omas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, dependin g on the histological type. Among 81 informative tumors assessed for LOH, t here seemed to be an associative trend between decreased nuclear and cytopl asmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These da ta support a role for PTEN in the pathogenesis of follicular thyroid tumors .