Trisomy 17 as a marker for a subset of noninvasive thyroid nodules with focal features of papillary carcinoma: cytogenetic and molecular analysis of 62 cases and correlation with histological findings.
BACKGROUND
Differentiated carcinomas of the thyroid are divided into follicular thyroid carcinoma and papillary thyroid carcinoma (PTC), based on their propensity to invade and their cytological features [papillary carcinoma-type nuclear changes (PTC-NCs)]. PTC typically exhibits a diploid karyotype sometimes with inv10(q11.2q21.2), leading to rearranged RET gene. Follicular thyroid carcinomas are often aneuploid and may exhibit t(2;3)(q13;p25), resulting in PAX8-PPARgamma1 gene fusion. Isolated trisomy 17 has rarely been reported in thyroid lesions, and its significance is unknown.


OBJECTIVE
Our objective was to determine whether isolated trisomy 17 corresponds to a specific histological or molecular thyroid tumor subset. Nine cases with isolated trisomy 17 were critically reviewed and investigated for RAS and BRAF mutations and for RET and PAX8-PPARgamma1 rearrangements.


RESULTS
All nine cases were noninvasive, exhibited follicular growth pattern, and showed PTC-NCs focally defined within the nodule: four were PTCs follicular variant within larger tumors, and five were follicular-patterned nodules with incomplete cytological features of papillary carcinoma (variable proportion of cells with PTC-NCs scattered inside the lesion). RAS, BRAF V600E mutation, RET or PAX8-PPARgamma1 rearrangements were not identified. One case had BRAF K601E mutation. Only two of the 53 control cases showed focal PTC-NCs.


CONCLUSIONS
Isolated trisomy 17 is associated with focal papillary carcinoma changes in follicular-patterned thyroid nodules and may be a marker for this subset of thyroid lesions that are often difficult to classify.
Frau
Daniela V
DV
Dipartimento di Scienze e Tecnologie Biomediche, University of Cagliari, 09042 Monserrato CA, Italy.
Lai
Maria L
ML
Caria
Paola
P
Dettori
Tinuccia
T
Coni
Pierpaolo
P
Faa
Gavino
G
Morandi
Luca
L
Tallini
Giovanni
G
Vanni
Roberta
R
D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D002886:Chromosomes, Human, Pair 17; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D014314:Trisomy / Q000235:genetics / Q000473:pathology*; D018631:ras Proteins / Q000235:genetics
D004273:DNA, Neoplasm; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins