Hepatocyte Nuclear Factor-1β Expression in Clear Cell Renal Cell Carcinoma and Urothelial Carcinoma With Clear Cell Features: A Potential Diagnostic Pitfall

Introduction: Distinguishing primary ovarian clear cell carcinoma (CCC) from other tumors with clear cell features can be challenging. Hepatocyte nuclear factor-1 beta (HNF-1 beta) is a sensitive and specific marker for ovarian CCC. Immunohistochemical studies have shown HNF-1 beta positivity in a substantial proportion of clear cell renal cell carcinoma (RCC), hepatocellular carcinomas, and clear cell pancreatic adenocarcinoma. This study was designed to evaluate the role of HNF-1 beta in differentiating ovarian CCC from metastatic RCC and urothelial carcinoma (UC) with clear cell features. Materials and Methods: Formalin-fixed paraffin-embedded tissue microarrays of 103 clear cell RCC, 8 UC with clear cell features, and 15 ovarian CCC were studied using an HNF-1 beta antibody. Nuclear staining intensity and percentage of positively stained cells were assessed and scored from 0 to 3. Percentage of positive staining was scored based on the proportion of tumor cells stained. Results: Sixty-three of 103 (61.2%) of clear cell RCC were positive for HNF-1 beta. Staining intensity was weak in 32 of 103 cases (31.6%), moderate in 21 of 103 cases (20.4%), and strong in 10 to 103 cases (9.7%). Six of 8 (75%) UC with clear cell features showed positive staining predominantly in clear cell areas. All 15 cases of ovarian CCC were positive for HNF-1 beta. Discussion: Overall 61.2% of clear cell RCC and 75% of UC were immunopositive with HNF-1 beta in our study. HNF-1 beta has a limited utility in differentiating CCC of the genitourinary system from an ovarian primary.