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.
Department of Medicine, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905, USA.
Mustafa
M
Sahin
Brandon L
BL
Allard
Martin
M
Yates
J Gregory
JG
Powell
Xiao-Li
XL
Wang
Ian D
ID
Hay
Ying
Y
Zhao
John R
JR
Goellner
Thomas J
TJ
Sebo
Stefan K G
SK
Grebe
Norman L
NL
Eberhardt
Bryan
B
McIver
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