Hepatocyte Nuclear Factor 1 Beta and Galectin 3 Are Useful Biomarkers for Distinguishing Subtypes of Renal Epithelial Neoplasia
Trevor A Flood, Brooke E Howitt, Paola Dal Cin, Michelle S Hirsch. Brigham and Women's Hospital, Boston, MA; Ottawa Hospital, Ottawa, ON, Canada
Background: Many renal epithelial neoplasms (RENs) demonstrate overlapping morphologic features. This is especially true for some of the more recently recognized subtypes of renal cell carcinoma (RCC), such as translocation RCC (trRCC), mucinous tubular and spindle cell carcinoma (MTSCC), and clear cell tubulopapillary RCC (CCTPRCC). Although traditional RCC biomarkers (i.e., CK7 and CD10) can be helpful, they are not entirely specific for distinguishing the different types of REN. Novel biomarkers such as galectin3 (Gal3) and hepatocyte nuclear factor 1beta (HNF1B) have been evaluated in only the most common subtypes of RCC, but have not been evaluated in the newer subtypes of RCC. This study set out to determine the sensitivity and specificity of Gal3 and HNF1B, as well as HNF1alpha (HNF1a) in a broad variety of RENs.
Design: 170 RENs were obtained for evaluation and immunohistochemical staining (IHC). Approximately 85% of these RENs had cytogenetic findings to support the morphologic diagnosis. Tumor classification included clear cell RCC (CCRCC), papillary RCC (PRCC), chromophobe RCC (chRCC), renal oncocytoma (RO), trRCC, MTSCC, CCTPRCC and metanephric adenoma (MA). IHC staining of tumors were assessed independently and semi-quantitatively as follows (HNF nuclear and GAL3 cytoplasmic): 0 no reactivity; 1+ <10%; 2+ 1125%; 3+ 26-50%; and 4+ >50%; a score of >2+ was considered a positive result.
Results: HNF1B was positive in all CCRCCs, PRCCs, ROs, MTSCCs, CCTPRCCs, and 75% and 80% of trRCCs and MAs, respectively. All 8 chRCCs were completely negative for HNF1B. HNF1a, which was less sensitive, less specific, and generally much weaker than HNF1B, stained 90% of CCRCCs, 45% of PRCCs, 25% of chRCCs, 60% of ROs, 75% of MTSCCs, 100% of CCTPRCCs, 75% of trRCCs, and 40% of MAs. GAL3 stained very few CCRCCs and PRCCs (6% and 13%, respectively), and was present in 80% of chRCCs, 67% of ROs, 60% of MTSCCs, 50% of CCTPRCCs, and 50% of trRCCs.
Conclusions: HNF1a was much weaker in staining intensity than HNF1B and did not prove to be as useful in distinguishing REN subtypes. Although HNF1B and GAL3 were not entirely specific, the absence of HNF1B and the presence of GAL3 in chRCCs is an important finding and can help distinguish it from other clear cell and oncocytic neoplasms such as CCRCC, MTSCC and RO. The presence of HNF1B and the low expression of GAL3 in CCRCC and PRCC can be helpful in confirming these diagnoses, especially when there are overlapping features with chRCC and MTSCC.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 141, Wednesday Morning