A novel microdissection and genotyping of follicular-derived thyroid tumors to predict aggressiveness.
Distinguishing thyroid follicular adenoma from minimally invasive or encapsulated angioinvasive carcinoma can be diagnostically challenging. In some cases, tumors are distorted, fragmented, or stripped of their capsule, and a definitive diagnosis becomes nearly impossible. In other cases, the foci of capsular and/or vascular invasion are subtle, thus making the diagnosis of carcinoma difficult. We developed a microdissection genotyping assay for assessing a panel of tumor-suppressor genes for loss of heterozygosity mutations. The frequency of allelic loss (FAL) in follicular-derived neoplasms correlates with the histologic aggressiveness of the tumor. Furthermore, we calculated the amount of genetic heterogeneity within each tumor, as a second important measure of a tumor's ability for clonal expansion and a surrogate marker for its malignant potential. The follicular adenomas had a low FAL (average 9%) and low intratumoral heterogeneity (5% variability). The minimally invasive and encapsulated angioinvasive carcinomas had an intermediate FAL (average 30%) and intermediate intratumoral heterogeneity (10% variability). The widely invasive carcinomas had a high FAL (average 53%) and high intratumoral heterogeneity (24% variability). Although a larger retrospective study is needed to correlate genotyping studies with patient outcome and prognosis, our results indicate that performing a mutational genotyping assay can stratify tumors into the histologically well-defined categories of adenomas, minimally invasive/angioinvasive carcinomas, and widely invasive follicular carcinomas.
University of Pittsburgh Medical Center, Pittsburgh, PA and University of Pennsylvania Medical Center, Philadelphia, PA 15213, USA.
Jennifer L
JL
Hunt
Virginia A
VA
Livolsi
Zubair W
ZW
Baloch
Patricia A
PA
Swalsky
Anke
A
Bakker
E
E
Sasatomi
Sydney
S
Finkelstein
E Leon
EL
Barnes
D000236:Adenoma / Q000235:genetics* / Q000473:pathology*; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004210:Dissection / Q000379:methods*; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D018598:Minisatellite Repeats; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
D017931:DNA Primers; D004273:DNA, Neoplasm