Detailed Immunohistochemical (IHC) Evaluation of Novel Markers Associated with Urothelial Differentiation in a Comprehensive Spectrum of Variants of Urothelial Carcinoma (UCa): A Study of 80 Cases.
Chandrakanth Annaiah, Gladell P Paner, Christian Gulmann, Priya Rao, Jae Y Ro, Donna E Hansel, Steven S Shen, Antonio Lopez-Beltran, Komal Arora, Rugvedita S Parakh, Loren P Herrera, Daniel J Luthringer, Jing Zhai, Yong M Cho, Mahul B Amin. Beaumont Hospital, Dublin, Ireland; University of Chicago, IL; Cedars-Sinai Medical Center, Los Angeles, CA; Cleveland Clinic, OH; The Methodist Hospital, Houston, TX; Faculty of Medicine, Cordoba, Spain; MD Anderson Cancer Center, Houston, TX
Background: Variants of UCa have diagnostic, prognostic, and therapeutic implications. Many of these variants present at metastatic sites and while dealing with variant morphology in the bladder, it is often important to rule out a metastatic tumor from other sites before the tumor is deemed to be a primary. IHC may play an important role, although expression of markers associated with urothelial differentiation has not been comprehensively evaluated in variants to date.
Design: 80 cases (26 micropapillary (MP), 7 nested, 2 microcystic, 2 clear cell, 11 plasmacytoid, 6 lymphoepithelioma-like (LELC),12 small cell and 14 sarcomatoid were evaluated with three urothelial-lineage associated (ULA) markers (GATA3, Uroplakin, S100P) and five markers supportive of urothelial differentiation (SUD) (thrombomodulin, CK7, CK20, p63, HMCK-34BE12). Immunoprofile was deemed diagnostic of urothelial differentiation if 2 of the 3 ULA markers or 3 of the 5 SUD markers were positive. % positivity was graded as 1 to 3+.
Results: Staining in urothelial variants was as follows: MP (90% ULA & 85% SUD); nested (57% ULA & 100% SUD); plasmacytoid (100% ULA & 70% SUD), microcystic (100% ULA and 50% SUD); clear cell U Ca (100% ULA & 100% SUD). Undifferentiated variants had lower positivity: small cell (0% ULA & 0% SUD); sarcomatoid (8 % ULA & 50% SUD); & LELC (17 % ULA & 83% SUD). Gata 3 & S100P were most commonly expressed ULA markers (84% & 96% in better differentiated variants respectively, & 23% & 31% in undifferentiated variants). Most commonly expressed SUD markers, besides CK7 were, p63 & HMCK (61% & 96% in better differentiated variants respectively, & 50% & 48% in undifferentiated variants).
Conclusions: This study presents the first comprehensive data of novel urothelial lineage markers with comparison to markers traditionally used to support urothelial differentiation in variant of UCa. The findings have important implications in the work-up of unusual primary bladder carcinomas & carcinomas at metastatic sites.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 177, Tuesday Morning