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PPAR Staining as a Surrogate for PAX8/PPAR Fusion Oncogene Expression in Follicular Neoplasms: Clinicopathological Correlation and Histopathological Diagnostic Value

Departments of Medicine (M.S., B.L.A., J.G.P., M.Y., X.-L.W., I.D.H., Y.Z., S.K.G.G., N.L.E., B.M.), Laboratory Medicine and Pathology (J.R.G., T.J.S., S.K.G.G.), and Biochemistry and Molecular Biology (N.L.E.), Mayo Clinic and Foundation, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Stefan Grebe, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. Email: grebs{at}mayo.edu.

The PAX8/PPAR (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 Hürthle cell carcinomas (HCC) from patients with complete clinical follow-up, to determine whether PPAR immunohistochemistry (as a surrogate of PAX8/PPAR expression) helps to distinguish FA from FTC and to assess its diagnostic accuracy as an adjunct to frozen section. We also correlated PPAR staining with clinical outcomes to assess its role as a prognostic marker.

PPAR 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 PPAR 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). PPAR staining was associated with favorable prognostic indicators (female gender, better tumor differentiation, and lesser risk of metastases).

PPAR 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). PPAR staining also shows an association with favorable prognosis and may have a role in risk stratification.

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