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PAX8 expression and TERT promoter mutations in the nested variant of urothelial carcinoma: a clinicopathologic study with immunohistochemical and molecular correlates.
Modern Pathology ( IF 6.365 ) Pub Date : 2020-01-13 , DOI: 10.1038/s41379-020-0453-z
Alexander S Taylor,Jesse K McKenney,Adeboye O Osunkoya,May P Chan,Hikmat A Al-Ahmadie,Daniel E Spratt,Douglas R Fullen,Arul M Chinnaiyan,Noah A Brown,Rohit Mehra

The nested variant of urothelial carcinoma, a frequent mimic of benign lesions on limited specimens, has been associated with high-stage disease including metastases at presentation. While PAX8 immunohistochemistry has been noted to be infrequently present in urothelial carcinoma in general, it has not been studied specifically in a cohort of nested urothelial carcinomas. Furthermore, TERT promoter mutation status is a potentially valuable biomarker for diagnosis of urothelial carcinoma and for noninvasive disease monitoring that has been observed in a majority of urothelial carcinoma and has previously been seen to be prevalent in multiple variant morphologies of urothelial carcinoma, including the nested variant. Twenty-five primary and three metastatic samples of nested urothelial carcinoma, along with 16 benign cases, were identified in a multicenter retrospective record review. PAX8 immunohistochemical stain was performed on all cases. In addition, TERT mutation analysis by allele-specific PCR was performed on 21 of the primary nested urothelial carcinoma cases and all benign cases. Positive PAX8 expression was identified in 52% (13 of 25) primary cases and 67% (2 of 3) metastatic cases of nested urothelial carcinoma; 50% (1 of 2) cases of large nested urothelial carcinoma were positive for PAX8. PAX8 expression was negative in the benign urothelium in all cases. TERT promoter mutation was observed in 83% (15 of 18) nested urothelial carcinoma cases and in 6% (1 of 16) of the benign cases. Recognition of the prevalence of positive PAX8 staining in this clinically relevant variant of urothelial carcinoma is essential to avoiding inaccurate or delayed diagnosis during the diagnostic workup of bladder lesions suspicious for nested variant of urothelial carcinoma. Moreover, the prevalence of TERT promoter mutations in nested urothelial carcinoma is similar to that of conventional urothelial carcinoma, further supporting its use as a biomarker that is stable across morphologic variants of urothelial carcinoma.
更新日期:2020-01-14

 

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