Interphase fluorescence in situ hybridization analysis detects a much higher rate of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic subgroups than conventional cytogenetics.

In benign thyroid lesions, three main cytogenetic subgroups, characterized by trisomy 7 or structural aberrations involving either chromosomal region 19q13.4 or 2p21, can be distinguished by conventional cytogenetics (CC). As a rule, these aberrations seem to be mutually exclusive. Interphase fluorescence in situ hybridization (I-FISH) analysis on benign as well as malignant thyroid neoplasias has been performed in the past, but rarely in combination with CC. In the present paper, we have analyzed 161 benign thyroid lesions both with CC and I-FISH on touch preparations by using a multi-target, triple-color FISH assay as well as dual-color break-apart probes for detection of the main cytogenetic subgroups. Within the samples, I-FISH detected tumors belonging to either of the subgroups more frequently than CC (23 vs. 11.4%), either due to small subpopulations of aberrant cells or to cryptic chromosomal rearrangements (three cases). Thus, I-FISH seems to be more sensitive than CC, particularly in the detection of subpopulations of cells harboring cytogenetic aberrations that may be overlooked by CC. In summary, I-FISH on touch preparations of benign thyroid lesions seems to be a favorable method for cytogenetic subtyping of thyroid lesions.

On the prevalence of the PAX8-PPARG fusion resulting from the chromosomal translocation t(2;3)(q13;p25) in adenomas of the thyroid.

The chromosomal translocation t(2;3)(q13;p25) characterizes a subgroup of tumors originating from the thyroid follicular epithelium and was initially discovered in a few cases of adenomas. Later, a fusion of the genes PAX8 and PPARG resulting from this translocation was frequently observed in follicular carcinomas and considered as a marker of follicular thyroid cancer. According to subsequent studies, however, this rearrangement is not confined to carcinomas but also occurs in adenomas, with considerably varying frequencies. Only five cases of thyroid adenomas with this translocation detected by conventional cytogenetics have been documented. In contrast, studies using reverse-transcription polymerase chain reaction (RT-PCR) detected fusion transcripts resulting from that translocation in an average of 8.2% of adenomas. The aim of this study was to determine the frequency of the PAX8-PPARG fusion in follicular adenomas and to use the HMGA2 mRNA level of such tumors as an indicator of malignancy. In cytogenetic studies of 192 follicular adenomas, the t(2;3)(q13;p25) has been identified in only two cases described herein. Histopathology revealed no evidence of malignancy in either case, and, concordantly, HMGA2 mRNA levels were not elevated. In summary, the fusion is a rare event in follicular adenomas and its prevalence may be overestimated in many RT-PCR-based studies.