Current Immunomarkers Are Inadequate for Accurate Classification of Renal Epithelial Tumors
Cigdem Himmetoglu Ussakli, Lawrence True. University of Washington, Seattle, WA
Background: There are 7 distinct variants of renal epithelial tumors in adults (WHO 2004): Clear cell(CC), papillary(PAP), chromophobe(CHR), collecting duct(CD), translocation(TC), mucinous tubular and spindle cell(MTSC) carcinomas; oncocytoma(ONC), and urothelial carcinoma(UC). Although these have unique molecular phenotypes, the histological features overlap. The immunophenotypes of these variants have been extensively studied to resolve the challenge of distinguishing them. We hypothesize that the immunophenotype, based on currently used antibodies(Ab), is not sufficiently specific to resolve the differential diagnosis of these variants.
Design: 57 articles reporting immunohistochemical profiles of primary adult renal epithelial tumors were reviewed, supplemented by our institutional experience. Only the 7 histological variants were included in the study. TCs were excluded due to presumed specificity of anti-TFE3 Ab. The most commonly used and/or investigated markers were selected for review. Expression percentages and cut-off values for positivity were based on the authors' criteria. The range of expression (as percentages) of each marker per tumor type was noted.
Results: Based on the literature expression of the 16 most frequently reported markers varies widely.
Expression of AMACR rules out CD and UC.CK5/6,p63 and/or HMWCK immunoreactivity supports a diagnosis of UC or CD.Expression of CAIX,CD117,CD15 and/or RCC marker rules out CD. The only marker unique to a tumor type is p63 (for UC). No other single marker is sufficiently specific for a tumor type to unequivocally categorize a histologically problematic case.
Conclusions: Since the distinction of renal epithelial tumors is important for clinical management and since clinical decisions are often based on needle biopsies, accurate distinction of these histological variants is of importance. Explanations for why the range of marker expression is so wide include different specificities of the antibodies, different sizes of specimens (TMAs vs whole tissue sections), different criteria for what is interpreted as positive, and the intrinsic heterogeneity of differentiation within each case. More specific tissue-based assays usable in formalin fixed tissue are needed for accurate classification of small samples of renal epithelial neoplasms.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 154, Tuesday Morning