PPARgamma staining as a surrogate for PAX8/PPARgamma fusion oncogene expression in follicular neoplasms: clinicopathological correlation and histopathological diagnostic value.
The PAX8/PPARgamma (PPFP) fusion-oncogene is moderately specific for follicular thyroid carcinomas (FTC). It remains unknown whether this can be translated into improved diagnosis, classification, or outcome prediction. We studied a cohort of well-characterized follicular adenomas (FA), FTC, and Hurthle cell carcinomas (HCC) from patients with complete clinical follow-up, to determine whether PPARgamma immunohistochemistry (as a surrogate of PAX8/PPARgamma expression) helps to distinguish FA from FTC and to assess its diagnostic accuracy as an adjunct to frozen section. We also correlated PPARgamma staining with clinical outcomes to assess its role as a prognostic marker.PPARgamma staining was more common in FTC (31 of 54; 57%) than in HCC (one of 23; 4%) or FA (four of 31; 13%) (P < 0.000001). Adjunctive use of PPARgamma immunohistochemistry improved diagnostic sensitivity of intraoperative frozen section from 84% to 96% (P < 0.05) but reduced specificity from 100% to 90% (P < 0.05). PPARgamma staining was associated with favorable prognostic indicators (female gender, better tumor differentiation, and lesser risk of metastases).PPARgamma staining may be helpful in the differential diagnosis of FA, FTC, and HCC, particularly when diagnostic sensitivity of histomorphology is reduced (e.g. during intraoperative frozen section). PPARgamma staining also shows an association with favorable prognosis and may have a role in risk stratification.
Sahin
Mustafa
M
Department of Medicine, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
Allard
Brandon L
BL
Yates
Martin
M
Powell
J Gregory
JG
Wang
Xiao-Li
XL
Hay
Ian D
ID
Zhao
Ying
Y
Goellner
John R
JR
Sebo
Thomas J
TJ
Grebe
Stefan K G
SK
Eberhardt
Norman L
NL
McIver
Bryan
B
D000236:Adenoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D009857:Oncogenes; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000032:analysis* / Q000235:genetics*; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D013194:Staining and Labeling; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators