Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in 
Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas, 
and thyroid tumors of follicular epithelium. PTEN has also been found to be 
somatically deleted, mutated, and/or silenced in various sporadically occurring 
cancers such as glioblastoma, breast cancer, kidney cancer, malignant melanoma, 
and endometrial cancer. Loss or reduction of PTEN protein expression as well as 
inappropriate subcellular compartmentalization is seen in non-medullary thyroid 
cancers. However, although allelic loss of the PTEN locus in 10q23.3 is 
frequently seen, this is not coupled with mutations in the PTEN gene. To 
approach further the frequency and mechanism behind PTEN silencing, we screened 
a panel of 87 sporadic thyroid tumors for PTEN mRNA expression, including 14 
anaplastic carcinomas, 37 follicular carcinomas, 21 atypical adenomas, and 15 
ordinary adenomas. Complete loss of PTEN mRNA expression was evident in six of 
the tumors, including four anaplastic carcinomas, one widely invasive carcinoma, 
and one ordinary adenoma. The transcriptional silencing of PTEN was 
significantly associated with the anaplastic subtype, suggesting that PTEN is 
involved in the carcinogenesis of highly malignant or late-stage thyroid 
cancers, whereas this particular mechanism appears to be of minor importance in 
differentiated follicular thyroid tumors. No association was observed between 
the expression, loss of heterozygosity, and mutation status in the 33 cases in 
which these parameters were compared. This indicates that PTEN silencing is a 
result of a wide variety of epigenetic and/or structural silencing mechanisms 
rather than a consequence of structural biallelic inactivation of the classical 
type. Furthermore, the high rate of alterations in the 10q23 region might 
indicate the presence of an as-yet unknown tumor-suppressor gene with an 
important role in the development of thyroid tumors.