A novel microdissection and genotyping of follicular-derived thyroid tumors to predict aggressiveness

Jennifer L. Hunt, Virginia A. Livolsi, Zubair W. Baloch, Patricia A. Swalsky, Anke Bakker, E. Sasatomi, Sydney Finkelstein, E. Leon Barnes

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)375-380
Number of pages6
JournalHuman Pathology
Volume34
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Keywords

  • Angioinvasion
  • Follicular carcinoma
  • Loss of heterozygosity
  • Minimally invasive follicular carcinoma
  • Mutation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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